Nicotinamide adenine dinucleotide (NAD+) biosynthetic pathway, mediated by nicotinamide phosphoribosyltransferase (NAMPT), a key NAD+ biosynthetic enzyme, plays a pivotal role in controlling many biological processes, such as metabolism, circadian rhythm, inflammation, and aging. Over the past decade, NAMPT‐mediated NAD+ biosynthesis, together with its key downstream mediator, namely the NAD+‐dependent protein deacetylase SIRT1, has been demonstrated to regulate glucose and lipid metabolism in a tissue‐dependent manner. These discoveries have provided novel mechanistic and therapeutic insights into obesity and its metabolic complications, (...) such as insulin resistance, an important risk factor for developing type 2 diabetes and cardiovascular disease. This review will focus on the importance of adipose tissue NAMPT‐mediated NAD+ biosynthesis and SIRT1 in the pathophysiology of obesity and insulin resistance. We will also critically explore translational and clinical aspects of adipose tissue NAD+ biology. (shrink)

Adipose tissue (AT) inflammation, a hallmark of the metabolic syndrome, is triggered by overburdened adipocytes sending out immune cell recruitment signals during obesity development. An AT immune landscape persistent throughout weight loss and regain constitutes an immune‐obesogenic memory that hinders long‐term weight loss management. Lipid‐associated macrophages (LAMs) are emerging as major players in diseased, inflamed metabolic tissues and may be key contributors to an obesogenic memory in AT. Our previous study found that LAM abundance increases with weight loss (...) via intermittent fasting (IF) in obese mice, which is driven by adipocyte p53 signalling. However, the specific signals causing LAM accumulation in AT under IF remain unknown. In this piece, we hypothesise on a range of adipocyte‐secreted signals that can harbor immune‐attractive features upon fasting/refeeding cycles. We highlight possible mechanisms including cell death signalling, matrikines, and other damage‐associated molecular patterns (DAMPs), as well as adipo(‐cyto)kines, lipid mediators, metabolites, extracellular vesicles, and epigenetic rewiring. Finally, we consider how advances in mechanisms of AT LAM recruitment gleaned from preclinical models might be translatable to long‐term weight management in humans. Thus, we provide vantage points to study signals driving monocyte recruitment, polarisation towards LAMs, and LAM retention, to harness the therapeutic potential of modulating AT LAM levels by impacting the immune‐obesogenic memory in metabolic disease. (shrink)

Despite promising early work into the role of immune cells such as eosinophils in adipose tissue (AT) homeostasis, recent findings revealed that elevating the number of eosinophils in AT alone is insufficient for improving metabolic impairments in obese mice. Eosinophils are primarily recognized for their role in allergic immunity and defence against parasitic worms. They have also been detected in AT and appear to contribute to adipose homeostasis and drive energy expenditure, but the underlying mechanisms remain elusive. (...) It has long been recognized that immune cells such as macrophages respond to external signals to regulate adipose homeostasis and energy balance, however, less is known about the relevance of eosinophil activity in AT. As the authors propose in this review, given recent debate over the relative importance of their tissue‐specific abundance, the stage is now set for exploring the functionality and activation states of AT eosinophils. (shrink)

Adipose tissue plays an important role in mammalian energy equilibrium not only as a lipid‐dissipating, i.e. energy‐storing, tissue (white adipose tissue), but also as an energy‐dissipating one (brown adipose tissue). Brown adipocytes have the ability of facultative heat production due to a unique mitochondrial protein, the uncoupling protein (UCP). Differentiation of white and (to a lesser extent) brown adipocytes has been studied in different cell culture systems, which has led to the identification of (...) external inducers, second messenger pathways and transcription factors involved in adipocyte differentiation. Functional differentiation of white adipocytes implies adipose conversion, whereas in brown adipocytes it insinuates additionally the development of a thermogenic function. This review discusses recent advances in the elucidation of the pathways responsible for, and the molecular bases of, adipose conversion on the one hand and development of the thermogenic properties of brown adipocytes on the other. (shrink)

MPZL3 is a nuclear‐encoded, mitochondrially localized, immunoglobulin‐like V‐type protein that functions as a key regulator of epithelial cell differentiation, lipid metabolism, ROS production, glycemic control, and energy expenditure. Recently, MPZL3 has surfaced as an important modulator of sebaceous gland function and of hair follicle cycling, an organ transformation process that is also governed by peripheral clock gene activity and PPARγ. Given the phenotype similarities and differences between Mpzl3 and Pparγ knockout mice, we propose that MPZL3 serves as a signaling hub (...) that is regulated by core clock gene products and/or PPARγ to translate signals from these nuclear transcription factors to the mitochondria to modulate circadian and metabolic regulation. Conservation between murine and human MPZL3 suggests that human MPZL3 may have similarly complex functions in health and disease. We summarize current knowledge and discuss future directions to elucidate the full spectrum of MPZL3 functions in mammalian physiology. (shrink)

Endothermic animals expend significant energy to maintain high body temperatures, which offers adaptability to varying environmental conditions. However, this high metabolic rate requires increased food intake. In conditions of low environmental temperature and scarce food resources, some endothermic animals enter a hypometabolic state known as torpor to conserve energy. Torpor involves a marked reduction in body temperature, heart rate, respiratory rate, and locomotor activity, enabling energy conservation. Despite their biological significance and potential medical applications, the neuronal mechanisms regulating torpor still (...) need to be fully understood. Recent studies have focused on fasting‐induced daily torpor in mice due to their suitability for advanced neuroscientific techniques. In this review, we highlight recent advances that extend our understanding of neuronal mechanisms regulating torpor. We also discuss unresolved issues in this research field and future directions. (shrink)

The recent discovery of the medullary circuit driving “hunger responses” – reduced thermogenesis and promoted feeding – has greatly expanded our knowledge on the central neural networks for energy homeostasis. However, how hypothalamic hunger and satiety signals generated under fasted and fed conditions, respectively, control the medullary autonomic and somatic motor mechanisms remains unknown. Here, in reviewing this field, we propose two hypothalamomedullary neural pathways for hunger and satiety signaling. To trigger hunger signaling, neuropeptide Y activates a group of neurons (...) in the paraventricular hypothalamic nucleus (PVH), which then stimulate an excitatory pathway to the medullary circuit to drive the hunger responses. In contrast, melanocortin‐mediated satiety signaling activates a distinct group of PVH neurons, which then stimulate a putatively inhibitory pathway to the medullary circuit to counteract the hunger signaling. The medullary circuit likely contains inhibitory and excitatory premotor neurons whose alternate phasic activation generates the coordinated masticatory motor rhythms to promote feeding. (shrink)

Intentional weight loss can increase health risk in the long‐term, despite short‐term benefits, because human adipose tissue is widely contaminated with various lipophilic environmental contaminants, especially persistent organic pollutants (POPs). Recently, chronic exposure to low POPs has emerged as a new risk factor for common metabolic diseases and cardiovascular diseases. The amount of POPs released from adipocytes to the circulation increases during weight loss, thereby increasing POPs exposure of other critical organs. Possible harmful effects due to release of (...) POPs during weight loss are opposite to those usually expected from losing weight. It is speculated that this tradeoff can explain recent puzzling findings on intensive weight loss. The presence of POPs in adipose tissue adds a challenge to weight management and an optimal strategy of weight management needs to consider both fat mass and dynamics of POPs. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:I am Not Obese. I am Just Fat.Sarah BrambletteMy body mass index classifies me as super morbidly obese, however my overall vital health statistics would indicate otherwise. I celebrated the American Medical Association’s classification of obesity as a disease for several reasons. First, obesity as a disease involves other medical complications of which I have none, so finally perhaps I can say I am not obese, I am just (...) fat. I am fat, as in my weight is caused by Lipedema and Lymphedema. Lipedema is a congenital condition, which causes my body to produce and accumulate abnormal amounts of adipose tissue in my legs, hips, thighs, and arms. There is not much known about Lipedema in the medical profession, even though it was identified in 1940 by doctors at the Mayo Clinic, and not many treatment options exist. Abnormal Lipedema tissue does not respond to restrictive caloric diet or exercise. Lymphedema is a condition of localized fluid retention and tissue swelling caused by a compromised lymphatic system. The second reason I celebrated obesity being classified as a disease was the hope that more research would be conducted on the actual causes and treatment of obesity and that research might include adipose tissue disorders. My vital health statistics are all normal, yet I still face challenges getting proper treatment in healthcare.My StoryAs I sat staring at the metal beast, I decided to make one final attempt to mount it. I placed my right foot on the step and used both hands to boost myself up, my lower legs were so large there was no room for my left foot. Immediately the exam table began to tip towards me, then slammed loudly against the tile floor as I quickly stepped off. It was a game of exam table teeter–totter I had played many times before and lost more often than won. I gave up, placed the sheet meant to cover my legs on the chair in the corner and squeezed myself down between its arms. The exam gown pinched my arms, barely covering the front of me and draped over my legs.My LegsOne of the main reasons I was seeing a new doctor, my first doctor visit in several years. My previous family doctor had retired. I was not ill, I was concerned. My weight had reached a point to where I was scared for my health and I wanted to get help and answers. I wanted answers about why my legs were so large and leaked fluid.The answer I got was one I had heard before “It’s your weight”.To the doctor’s credit, she did explain it a bit more, she said the fluid in my legs was due to my excess weight putting pressure on my legs. However, she did not actually know how much I weighed. The scale in her office only went to 350lbs, and even with the add–on weight it could not register a weight for me, so we only knew I weighed more than 400lbs. I asked her if she knew if the hospital or another office had a scale that could weigh me. She did not. She may have sent me home with a prescription for a diuretic, I do not remember. I know I was not sent home with any help for my weight or my legs, just a follow–up appointment. It was during that follow up appointment that I advocated for myself and asked if she would refer me for physical therapy, so that I could do some safe and monitored exercise. She agreed, and I began physical therapy in the pool.At the pool I met other people who looked similar to my size. I noticed their legs were normal size and wondered why? Then I thought about sumo wrestlers. Sumo wrestlers weigh hundreds of pounds and their legs are normal too. What was wrong with my legs? One day I heard a man in the pool tell another [End Page 85] patient that he had lost weight. I wondered where he was able to weigh himself, and hoped it was not rude to ask him. He told me... (shrink)

Dysregulation of lipid metabolism is a commonly observed feature associated with metabolic syndrome and leads to the development of negative health outcomes such as obesity, diabetes mellitus, non‐alcoholic fatty liver disease, or atherosclerosis. Time‐restricted feeding/eating (TRF/TRE), an emerging dietary intervention, has been shown to promote pleiotropic health benefits including the alteration of diurnal expression of genes associated with lipid metabolism, as well as levels of lipid species. Although TRF likely induces a response in multiple organs leading to the modulation of (...) lipid metabolism, a majority of the studies related to TRF effects on lipids have focused only on individual tissues, and furthermore there is a lack of insight into potential underlying mechanisms. In this review, we summarize the current insights regarding TRF effects on lipid metabolism and the potential mechanisms in adipose tissue, liver, skeletal muscle, and heart, and conclude by outlining possible avenues for future exploration. (shrink)

Fermented dairy products such as yogurt contain many bioactive compounds. In addition, probiotic yogurts are an invaluable source of probiotic bacteria and are a group of probiotic products best accepted by children. There is plenty of research indicating an interdependence between yogurt consumption, body mass index, and adipose tissue percentage, which suggests that yogurt consumption may contribute to reducing the risk of becoming overweight or obese. In turn, the occurrence of overweight and obesity may be accompanied by a (...) reduced sensitivity to sweetness, which modifies food preference selection and acceptance, including with yogurt. This study aimed to assess the preferences and consumption of yogurt in terms of sensitivity to recognize sweetness and obesity in a group of 7–9-year-old children. Body mass index and adipose tissue percentage obesity indicators were determined, and the frequency of fermented milk product consumption was assessed about the results of the sweetness recognition test as well as yogurt preferences. There was no significant relationship between body weight and the frequency of fermented milk product consumption. Correlations were found between the values of body mass index and the ability to recognize sweetness, which was significantly better recognized by underweight children or at normal body weight, moreover, those children with a higher ability to recognize sweetness significantly more frequently preferred plain unsweetened yogurt. (shrink)

Bone‐marrow mesenchymal stem cell (BM‐MSC) proliferation and lineage commitment are under the coordinated control of metabolism and epigenetics; the MSC niche contains low oxygen, which is an important determinant of the cellular metabolic state. In turn, metabolism drives stem cell fate decisions via alterations of the chromatin landscape. Due to the fundamental role of BM‐MSCs in the development of adipose tissue, bones and cartilage, age‐associated changes in metabolism and the epigenome perturb the balance between stem cell proliferation and (...) differentiation leading to stem cell depletion, fat accumulation and bone‐quality related diseases. Therefore, understanding the dynamics of the metabolism‐chromatin interplay is crucial for maintaining the stem cell pool and delaying the development and progression of ageing. This review summarizes the current knowledge on the role of metabolism in stem cell identity and highlights the impact of the metabolic inputs on the epigenome, with regards to stemness and pluripotency. (shrink)

Organisms must adapt to environmental stresses to ensure their survival and prosperity. Different types of stresses, including thermal, mechanical, and hypoxic stresses, can alter the cellular state that accompanies changes in gene expression but not the cellular identity determined by a chromatin state that remains stable throughout life. Some tissues, such as adipose tissue, demonstrate remarkable plasticity and adaptability in response to environmental cues, enabling reversible cellular identity changes; however, the mechanisms underlying these changes are not well understood. (...) We hypothesized that positive and/or negative “Integrators” sense environmental cues and coordinate the epigenetic and transcriptional pathways required for changes in cellular identity. Adverse environmental factors such as pollution disrupt the coordinated control contributing to disease development. Further research based on this hypothesis will reveal how organisms adapt to fluctuating environmental conditions, such as temperature, extracellular matrix stiffness, oxygen, cytokines, and hormonal cues by changing their cellular identities. (shrink)

Obesity is characterized by the accumulation of an excessive amount of fat mass in the adipose tissue, subcutaneous, or inside certain organs. The risk does not lie so much in the amount of fat accumulated as in its distribution. Abdominal obesity is an important risk factor for cardiovascular diseases, diabetes, and cancer, having an important role in the so-called metabolic syndrome. Therefore, it is necessary to prevent, detect, and appropriately treat obesity. The diagnosis is based on anthropometric indices (...) that have been associated with adiposity and its distribution. Indices themselves, or a combination of some of them, conform to a big picture with different values to establish risk. Anthropometric indices can be used for risk identification, intervention, or impact evaluation on nutritional status or health; therefore, they will be called anthropometric health indicators. We have found 17 AHIs that can be obtained or estimated from 3D human shapes, being a noninvasive alternative compared to X-ray-based systems, and more accessible than high-cost equipment. A literature review has been conducted to analyze the following information for each indicator: definition; main calculation or obtaining methods used; health aspects associated with the indicator ; criteria to classify the population by means of percentiles or cutoff points, and based on variables such as sex, age, ethnicity, or geographic area, and limitations. (shrink)

Platelets have important hemostatic functions in repairing blood vessels upon tissue injury. Cytokines, growth factors, and metabolites stored in platelet α‐granules and dense granules are released upon platelet activation and clotting. Emerging evidence indicates that such platelet‐derived signaling factors are instrumental in guiding tissue regeneration. Here, we discuss the important roles of platelet‐secreted signaling factors in skeletal muscle regeneration. Chemokines secreted by platelets in the early phase after injury are needed to recruit neutrophils to injured muscles, and impeding (...) this early step of muscle regeneration exacerbates inflammation at later stages, compromises neo‐angiogenesis and the growth of newly formed myofibers, and reduces post‐injury muscle force production. Platelets also contribute to the recruitment of pro‐regenerative stromal cells from the adipose tissue, and the platelet releasate may also regulate the metabolism and proliferation of muscle satellite cells, which sustain myogenesis. Therefore, harnessing the signaling functions of platelets and the platelet secretome may provide new avenues for promoting skeletal muscle regeneration in health and disease. (shrink)

Knowledge about eating habits is relevant for understanding the relations between diet, obesity and development of Chronic Non-Communicable Diseases. The storage of calories as body fat, mainly in the visceral subcutaneous adipose tissue, as consequence of hypercaloric diet poor in nutrients, is responsible for increasing sublinic inflammation and overloading the immune system. Diet plays an important role in reducing inflammation. In time of infectious pandemia, of the new corona virus (COVID-19), the food quality and nutritional status of Brazilians (...) may interfere in fighting this infection. Based on the literature, this article aims to discuss the Brazilians eating habbits and nutritional status. The data shows that Brazilian are gainning weight and tend to a diet poor in nutrient intake. Consequently this scenario favors the subclinical inflammation and the weakness of the immune response. We suggest that Brazilian Health Authorities pay attention to this issue. (shrink)

Emerging data connects the aging process in dermal fibroblasts with metabolic reprogramming, provided by enhanced fatty acid oxidation and reduced glycolysis. This switch may be caused by a significant expansion of the dermal white adipose tissue (dWAT) layer in aged, hair‐covered skin. Dermal adipocytes cycle through de‐differentiation and re‐differentiation. As a result, there is a strongly enhanced release of free fatty acids into the extracellular space during the de‐differentiation of dermal adipocytes in the catagen phase of the hair (...) follicle cycle. Both caveolin‐1 and adiponectin are critical factors influencing these processes. Controlling the expression levels of these two factors also offers the ability to manipulate the metabolic preferences of the different cell types within the microenvironment of the skin, including dermal fibroblasts. Differential expression of adiponectin and caveolin‐1 in the various cell types may also be responsible for the cellular metabolic heterogeneity within the cells of the skin. (shrink)

Physiological investigation has demonstrated that the central nervous system monitors body composition and adjusts energy intake and expenditure to stabilize total adipose tissue mass. Genetic variations in the signalling molecules involved in this regulatory system account for the heritable component of body fat content. The application of molecular techniques to rodent models of Mendelian obesity has resulted in the characterization of five loci at which mutations produce an abnormal accumulation of body fat. The genes at these loci include (...) agouti, which encodes a molecule that antagonizes the binding of alpha melanocyte‐stimulating hormone to its receptor; fat, which encodes carboxypeptidase E; tubby, which encodes a putative phosphodiesterase; obese, which encodes a circulating satiety protein; and diabetes, which encodes the receptor for the obese gene product. A more detailed understanding of the functional interrelationships of these genes should lead to important new insights into the causes and potential therapies for human obesity. (shrink)

RESUMEN El presente texto es el resultado de un estudio dirigido a demostrar la importancia del sistema muscular en mujeres operadas de cáncer de mama, enfermedad con elevada incidencia en Cuba y el mundo. Se investigó en los principales reportes anatómicos. Se partió de la revisión documental de textos básicos para la carrera de Medicina inherentes a la asignatura Anatomía Humana. Se corroboró que autores como M. Prives, N Lisenkov y V Bushkovich y R. D. Sinelnikov; describen los músculos, pero (...) no relatan su importancia en la práctica quirúrgica. Se emplearon los buscadores en Internet y otros sitios webs de información científica, que permitieron corroborar desde un enfoque de ciencia, tecnología y sociedad la importancia del tejido muscular y su aplicación en técnicas reconstructivas en pacientes operadas de cáncer de mama. Se constató que los músculos más usados son los rectos abdominales, los dorsales anchos, los gráciles y el tejido adiposo del pliegue glúteo. ABSTRACT The present text is the result of a study directed to demonstrate the importance of the muscular system in women who had a surgery on breast cancer, illness with high incidence in Cuba and the world. It was investigated in the principal anatomical reports. It began with the documentary review of basic texts for the career of Medicine inherent to the subject Human Anatomy. It was corroborated that authors like M. Prives, N Lisenkov and V Bushkovich and R. D. Sinelnikov; they describe the muscles, but they do not report their importance in surgical practice. It was used the searche engines on Internet and other web sites of scientific information, which allowed to corroborate from an approach of science, technology and society the importance of the muscular tissue andits application in reconstructive techniques in patients who undergoa breast cancer surgery. It was stated that the most used muscles are the abdominal rectus, the latissimusdorsi, the graceful ones and the adipose tissue of the gluteus fold. (shrink)

The prevalence of obesity skyrocketed over the past decades to become a significant public health problem. Obesity is recognized as a low-grade inflammatory disease and is linked with several comorbidities such as diabetes, circulatory disease, common neurodegenerative diseases, as well as chronic pain. Adipocytes are a major neuroendocrine organ that continually, and systemically, releases pro-inflammatory factors. While the exact mechanisms driving obesity-induced pain remain poorly defined, nociceptors hypersensitivity may result from the systemic state of inflammation characteristic of obesity as well (...) as weight surplus-induced mechanical stress. Obesity and pain also share various genetic mutations, lifestyle risk factors, and metabolic pathways. For instance, fat pads are often found hyper-innervated and rich in immune cell types of multiple origins. These immunocytes release cytokines, amplifying nociceptor function, which, in turn, via locally-released neuropeptides sustain immunocytes’ function. Here, we posit that along with mechanical stressed stemming from extra weight, the local neuro-immune interplay occurring within the fat pads maintains the state of chronic low-grade inflammation and heightens sensory hypersensitivity. Overall, stopping the harmful neuro-immune crosstalk may constitute a novel pathway to prevent obesity-associated comorbidities, including neuronal hypersensitivity. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Dialectical Tension Between Gloomy and Rosy Prospects of Behavioral GeneticsAwais Aftab, MD (bio)Turkheimer and Greer’s article “Spit for Science and the Limits of Applied Psychiatric Genetics” (2024) offers a devastating critique of the state of psychiatric genetics, using Spit for Science (S4S) as a case study. I have read the paper many times in the process of writing this commentary, and each time I am left inarticulate. Nonetheless, I (...) hope that my comments, from the point of view of a practitioner who operates at the intersection of clinical psychiatry, psychiatric science, and philosophy of psychiatry, will be of some value to the discussion. I have no substantial disagreements with Turkheimer and Greer. The main point I wish to convey is that there is reason to hope that findings from genetic research will contribute to clinical progress in psychiatry in an incremental and iterative manner, but because psychiatric genetics has overpromised and underdelivered, we find ourselves vacillating between bullish and bearish moods.Some critics may say that the choice to selectively focus on S4S is unfair, or that it gives a misleading impression of the current state of psychiatric genetics. The launch and implementation of S4S captures a particular moment in the history of psychiatric genetics when it was known that individual associations will be small and that large samples will be needed for significant associations, but it was not appreciated exactly how small and how large respectively. Initial estimates of sample sizes needed for successful genetic associations turned out to be wildly inadequate. Progress occurred only with unprecedented international collaboration and extremely large sample sizes. For example, a 2022 genome-wide association study (GWAS) of schizophrenia included more than 76,000 people with schizophrenia and 240,000 controls (Trubetskoy et al., 2022)! S4S is one project from one institution. It is understandable in retrospect that a sample of 10,000 freshmen could only have delivered so much. It may be argued that whatever the promise of psychiatric genetics as a field, it is not constrained by the success or failure of S4S.On the one hand, it is true that S4S did not have the requisite sample size. On the other hand, the contemporary understanding of the genetics of alcohol use has not improved on insights from S4S by that much (Deak et al., 2019). SNP-based heritability estimate of problematic alcohol use [End Page 451] is close to 10% based on a GWAS of 435,000 individuals (Zhou et al., 2020), consistent with statistically non-significant estimates from S4S. The same GWAS has identified 29 risk variants, and genetic correlations with more than a hundred other phenotypes. Transcriptomic analysis has revealed that implicated genes are expressed in the brain but also in gastrointestinal, adipose, and liver tissue, pointing toward pathways of protection and vulnerability. A polygenic risk score (PRS) derived from associated variants is consistently and significantly associated with alcohol dependence, with variance explained ranging from 0.77% to 2.12% in different samples (Zhou et al., 2020).At present, PRS for problematic alcohol use has little predictive value at the individual level and is practically worthless from the standpoint of clinical practice. There are hints that genetic associations can point toward brain mechanisms involved in alcohol use disorder, but we have little to show for it yet. That PRS will achieve clinical utility is not guaranteed but neither is it impossible. A PRS for externalizing behavior explains approximately 10% of the variance, which is on par with factors such as socioeconomic status and neighborhood disadvantage (Karlsson Linnér et al., 2021). And even if PRS does not become a common part of clinical practice, it can still be a useful tool in clinical research. With regard to understanding mechanisms, the trivial effect size of the genetic association is by itself irrelevant. This point is made eloquently by Steven HymanWhen used as a tool to associate a trait with biology, the effect size of the allele on the ultimate phenotype does not matter… what makes a gene product a good drug target is not the effect size of the associated allele, but its overall role in biology… Once a pathway is shown to... (shrink)

BackgroundDepression is a serious mental disorder often accompanied by emotional and physiological disorders. Visceral fat index is the current standard method in the evaluation of visceral fat deposition. In this study, we explored the association between VAI and depression in the American population using NHANES data.MethodsA total of 2,577 patients were enrolled for this study. Data were collected through structured questionnaires. Subgroup analysis for the relationship between VAI and depression was evaluated using multivariate regression analysis after adjustment for potential confounding (...) factors.ResultsFor every 1 unit increase in VAI, the clinical depression increased by 14%. High VAI scores increased the highest risk of developing depression. Subgroup analysis demonstrated a strong and stable association between VAI and the development of depression.ConclusionOur study showed that depressive symptoms are associated with a high ratio of visceral adiposity index after controlling confounding factors. (shrink)

More and more areas of medicine involve subjects donating tissues to another — blood, organs, bone marrow, sperm, ova and embryos can all be transferred from one person to another. Within the technical frameworks of biomedicine, such fragments are generally treated as detachable things, severed from social identity once they are removed from a particular body. However an abundant anthropological and sociological literature has found that, for donors and patients, human tissues are not impersonal. They retain some of the values (...) of personhood and identity, and their incorporation often has complex effects on embodied identity. This article draws on feminist philosophy of the body to think through the implications of some of these practices. Specifically, it draws on the idea of intercorporeality, wherein the body image is always the effect of embodied social relations. While this approach is highly productive for considering the stakes involved in tissue transfer, it is argued that the concept of body image has been too preoccupied with the register of the visual at the expense of introceptive data and health/illness events. Empirical data around organ transplant and sperm donation are used to demonstrate that the transfer of biological fragments involves a profound kind of intercorporeality, producing identifications and disidentifications between donors and recipients that play out simultaneously at the immunological, psychic and social levels. (shrink)

The somatic mutation theory (SMT) of cancer has been and remains the prevalent theory attempting to explain how neoplasms arise and progress. This theory proposes that cancer is a clonal, cell‐based disease, and implicitly assumes that quiescence is the default state of cells in multicellular organisms. The SMT has not been rigorously tested, and several lines of evidence raise questions that are not addressed by this theory. Herein, we propose experimental strategies that may validate the SMT. We also call attention (...) to an alternative theory of carcinogenesis, the tissue organization field theory (TOFT), which posits that cancer is a tissue‐based disease and that proliferation is the default state of all cells. Based on epistemological and experimental evidence, we argue that the TOFT compellingly explains carcinogenesis, while placing it within an evolutionarily relevant context.magnified imagemagnified imageAna Soto and Carlos Sonnenschein are at Tufts University School of Medicine, Boston, MA, USA. (shrink)

Health research is increasingly being conducted on a global scale, particularly in the developing world to address leading causes of morbidity and mortality. While research interest has increased, building scientific capacity in the developing world has not kept pace. This often leads to the export of human tissue (defined broadly) from the developing to the developed world for analysis. These practices raise a number of important ethical issues that require attention.

Age‐related and cancer‐related epigenomic modifications have been associated with enhanced cell‐to‐cell gene expression variability that characterizes increased cellular stochasticity. Since gene expression variability appears to be highly reduced by—and epigenetic and phenotypic stability acquired through—direct or long‐range cellular interactions during cell differentiation, we propose a common origin for aging and cancer in the failure to control cellular stochasticity by cell–cell interactions. Tissue‐disruption‐induced cellular stochasticity associated with epigenetic drift would be at the origin of organ dysfunction because of an increase (...) in phenotypic variation among cells, ultimately leading to cell death and organ failure through a loss of coordination in cellular functions, and eventually to cancerization. We propose mechanistic research perspectives to corroborate this hypothesis and explore its evolutionary consequences, highlighting a positive correlation between the median age of mass loss onset (a proxy for the onset of organ aging) and the median age at cancer diagnosis. (shrink)

The controversies in Bristol, Alder Hey and elsewhere in the UK surrounding the removal and retention of human tissue and organs have led to extensive law reform in all three UK legal systems. This paper reports a short study of the reactions of a range of health professionals to these changes. Three main areas of ethical concern were noted: the balancing of individual rights and social benefit; the efficacy of the new procedures for consent; and the helpfulness for professional (...) practice of the new legislation and regulation. Recognition of these concerns may help in forging a new partnership between professionals and patients and their families. (shrink)

Testicular tissue cryopreservation aims to preserve the future option of genetic reproduction for prepubescent cancer patients who are at risk of infertility as a result of their cancer therapies. This technology is experimental and currently only offered in the research context. As TTCP moves towards becoming more widely available, it is imperative that healthcare providers recognize the complex ethical issues surrounding this technology. This scoping review study identifies and assesses the range and depth of ethical concerns related to this (...) testicular tissue cryopreservation technology. At present, no such scoping review of ethical concerns exists in the TTCP literature. The forty-three full-text articles included in this study yielded twenty-two different ethical considerations discussed in relation to TTCP. It was observed that these ethical considerations fit within a mainstream Principlism approach to bioethics. Accordingly, there are ethical gaps in the TTCP literature that can be identified with alternative moral lenses. In particular, it was found that ethical concerns related to context and relational aspects of identity were absent in nearly all ethical examinations of TTCP. Furthermore, only 9 per cent of articles reviewed in this study focused primarily on the ethics of TTCP, thus demonstrating a need for further in depth ethical analyses of this technology. The results of this study are important for supporting the ethical provision of TTCP and can contribute to policy and guideline development. The findings of this study demonstrate the need for greater depth and diversity in analyses of ethical considerations related to this technology. (shrink)

Ex-vivo tissue engineering is a quickly developing medical technology aiming to regenerate tissue through the introduction of an ex-vivo created tissue construct instead of restoring the damaged tissue to some level of functionality. Tissue engineering is considered by some as a new medical paradigm. We analyse this claim and identify tissue engineering’s fundamental characteristics, focusing on the aim of the intervention and on the complexity and continuity of the process. We inquire how these features (...) have an impact not only on the scientific research itself but also on the ethical evaluation of this research. We suggest that viewing tissue engineering as a new medical paradigm allows us to develop a wider perspective for successful investigation instead of focusing on isolated steps of the tissue engineering process in an anecdotal way, which may lead to an inadequate ethical evaluation. We argue that the concept of tissue engineering as a paradigm may benefit the way we address the ethical challenges presented by tissue engineering. (shrink)

One important sense of 'global ethics' concerns the applied ethical issues arising in the context of economic globalisation. This article contends that we are beginning to witness the economic commodification and, concomitantly, the globalisation, of human tissue and the human genome. Policy-makers and local research ethics committees need to be aware that the relevant ethical questions are no longer confined to their old national or subnational context. A shift from questions of personal autonomy and identity can therefore be expected-towards (...) the more problematic issues of justice, exploitation and distribution. Here we can learn from the distinctions drawn in legal philosophy, such as the notion of property as a 'bundle' of rights, from which we may choose rights favouring the interests of vulnerable populations. We may also wish to apply the distinctions drawn by Calabresi and Melamed between pure property rules, modified alienability rules, and pure non-property regimes. Global ethics also concerns issues of value disparity across cultures, directing our attention to the moral beliefs of indigenous peoples, for example, whose DNA or tissue is increasingly of commercial importance. In examining case examples from Tonga and Aotearoa/new Zealand, I will consider the impact of indigenous belief systems and of neo-colonialism on indigenous peoples' perceptions of Western researchers. It is clear that many indigenous peoples reject both the pure property system and any modifications, insisting on a pure non-property regime. How can they then be protected in a globalised market system that so far favours the opposite end of the spectrum? (shrink)

There are complex unresolved ethical, legal and social issues related to the use of human tissues obtained in the course of research or diagnostic procedures and retained for further use in research. The question of intellectual property rights over commercially viable products or procedures that are derived from these samples and the suitability or otherwise of participants relinquishing their rights to the samples needs urgent attention. The complexity of these matters lies in the fact that the relationship between intellectual property (...) rights and ownership or rights pertaining to the samples on which the intellectual property right is based may either be overlooked or taken for granted. What equally makes the matter complex is that samples may be obtained from participants in developing countries and exported to developed countries for analysis and research. It is important for research ethics committees to tread carefully when reviewing research protocols that raise such issues for purposes of ensuring that appropriate benefit sharing agreements, particularly with developing countries, are in place.This paper attempts to analyse the key questions related to ownership and intellectual property rights in commercially viable products derived from human tissue samples. Patent law is used as a point of reference as opposed to other forms of intellectual property rights such as industrial designs because it is the right that most inventors apply for in respect of human tissue-related inventions. The key questions are formulated following a systematic analysis of peer reviewed journal articles that have reported original investigations into relevant issues in this field. Most of the cases and reported studies that are referred to in this paper do not directly deal with HIV/AIDS research but the underlying principles are helpful in HIV/AIDS research as well. Pertinent questions, which members of ethics review committees should focus on in this regard are discussed and suggestions on appropriate approaches to the issues are proposed in the form of specific questions that an ethics review committee should consider. Specific recommendations regarding areas for further research and action are equally proposed. (shrink)

Obesity is a worldwide epidemic associated with severe health and psychological wellbeing impairments expressed by an increased prevalence of affective disorders. Emotional dysfunction is important due to its effect on social performance. The aim of the present narrative review is to provide a general overview of human research exploring emotional information processing in overweight and obese people. Evidence suggests that obesity is associated with an attenuation of emotional experience, contradictory findings about emotion recognition, and scarce research about automatic emotional information (...) processing. Finally, we made some concluding considerations for future research on emotional information processing in overweight and obese people. (shrink)

We have rapidly gained insights into the presence and function of T lymphocytes in non‐lymphoid tissues, the tissue‐resident memory T (TRM) cells. The central pillar of adaptive immunity has been expanded from classic central memory T cells giving rise to progeny upon reinfection and effector memory cells circulating through the blood and patrolling the tissues to include TRM cells that reside and migrate inside solid organs and tissues. Their development and maintenance have been studied in detail, providing exciting clues (...) on how their unique properties used to fight infections may benefit therapies against solid tumors. We provide an overview of CD8 TRM cells and the properties that make them of interest for vaccination and cancer therapies. (shrink)

Three-dimensional ‘bioprinting’ is under development, which may produce living human organs and tissues to be surgically implanted in patients. Like tissue engineering and regenerative medicine generally, the process of bioprinting potentially disrupts experience of the human body by redefining understandings of, and becoming actualised in new practices and regimes in relation to, the body. The authors consider how these novel sociotechnical imaginaries may emerge, having regard to law’s contribution to, as well as its possible transformation by, the process of (...) 3D bioprinting. The authors draw on Gilbert Simondon and corporeal, material feminists to account for these disruptions as ‘ontogenetic,’ in the sense that technology can produce new ontologies or beings. The authors focus namely on ontogenesis, individuation and the pre-individual forces that comprise, and yet remain inexhausted by, the process of 3D bioprinting. The authors argue legal phenomena are pre-individual forces that ‘in-form’ ontogenesis. These pre-individual forces are indistinguishable from those implicated in the individuation of the body’s physical form; thereby, the individuation of the bodily material through 3D bioprinting may be expressive and generative of sociolegal phenomena, at least as those relate to the body. The authors conclude that 3D bioprinting shores up conventional, liberal conceptions in law of the human body as individual, bounded and primarily contractual. Three-dimensional bioprinting may introduce ontological difference to the extent it promises and realises a new temporality of the human as a species- and legal-subject, although such a development would only seem to expand, rather than attenuate, a biopolitical regime. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Fetal Tissue ResearchMary Carrington Coutts (bio)I. IntroductionThe use of tissue from fetal remains for transplantation and biomedical research has become a controversial issue in recent years, involving scientists, doctors, patients, and the federal government. Fetal tissue is potentially useful in a wide range of treatments for a number of serious diseases, some of them affecting millions of people. Despite the promise, transplantation research using fetal (...) class='Hi'>tissue from induced abortion slowed dramatically in the U.S. in 1988, when a moratorium was declared on federal funding for such research involving humans. That moratorium was lifted by President Clinton on January 21, 1993. Though the future of fetal tissue transplantation research is brighter, public debate on the issue is likely to continue, exacerbated by the "acrimonious abortion debate" (VI, Post 1991, p. 14).Using fetal tissue in biomedical research and in transplantation is not a new practice. As early as 1928 unsuccessful attempts were made to transplant fetal pancreas cells into diabetics (VII, Fichera 1928). Fetal tissue was used effectively in biomedical research during the 1950s, and was instrumental in the culture of the polio virus, which led to the development of the polio vaccine. Fetal tissue cultures were also essential in the development of the rubella vaccine, and continue to be used in virology research. Transplantation of fetal thymus cells into patients with DiGeorge Syndrome has been recognized as effective therapy since the late 1960s.Many of the therapeutic applications involving fetal tissue are still experimental, so it is difficult to pinpoint fetal tissue transplantation's therapeutic potential. One promising application is the transplantation of human fetal brain cells into the substantia nigra of patients with Parkinson's disease to restore motor function. Fetal neural transplants have also shown promise for patients suffering from Alzheimer's disease, spinal cord and other neural tissue injuries, and possibly some forms of cortical blindness. Fetal liver cells may be useful for treatment of some kinds of bone marrow disease seen in leukemia and aplastic anemia patients. [End Page 81] Fetal tissue transplantation may also help those suffering from blood clotting disorders, such as sickle cell anemia, thalassemia, and hemophilia. Fetal pancreatic tissue has potential applications in the treatment of diabetes, especially juvenile onset diabetes. Human gene therapy may also employ embryonic and early fetal cells.The Center for Biomedical Ethics at the University of Minnesota reports that more than 1,000 patients have received transplanted fetal tissue worldwide. Countries where fetal tissue transplantation has occurred include: Australia, Canada, China, the Commonwealth of Independent States (formerly the U.S.S.R.), Cuba, Czechoslovakia, Finland, France, Germany, Great Britain, Hungary, India, Italy, Mexico, Norway, Spain, Sweden, and Yugoslavia (IV, Vawter 1992, p. 2; I, Spain 1988; VII, Reinikainen 1989).Fetal tissue has unique characteristics that make it especially valuable in some treatments. Fetal cells develop much faster than adult cells, hastening the therapeutic effect—a potentially significant benefit for gravely ill patients. They are also less likely to be rejected by transplant recipients because they are less antigenic than adult cells. This reduces the need for the exact tissue matches that can be so difficult to obtain. Fetal tissue is also easier to culture and proliferates more readily than comparable adult tissue. Furthermore, fetal tissue is in greater supply, due to the number of elective abortions.Questions about the use of fetuses and fetal tissue in biomedical research were raised in the United States in the early 1970s. Between 1969 and 1973, all 50 states enacted the Uniform Anatomical Gift Act, allowing for the donation of all or part of the body of a dead fetus for research or therapeutic research. Prospects for the use of fetal tissue increased after the Supreme Court decision in Roe v. Wade legalized abortion. As the availability of fetal tissue increased so did the concern over the potential for controversial research on living, soon-to-be-aborted fetuses, and anxiety over maltreatment of dead abortuses. Vivid examples include Geoffrey Chamberlain's 1968 report of an experiment on a fetus of 26 weeks gestational age. Delivered by hysterotomy from a 14-year-old patient, the fetus was attached to an "artificial placenta" and kept alive for more than... (shrink)

Tissue typing (TT) is a recent and controversial scientific advance. Whilst its current applications can easily be described as protherapeutic and within the realms of preventative medicine,1 its specificity and potential are often characterized as the tip of the eugenic iceberg: undermining the very basis of individual autonomy and identity in an inevitable march towards the perfect society:2 In addition to arguments concerning societal harms flowing from TT, significant concerns have also been raised concerning harms to the future child (...) born as a result. In the context of current legislation and policy, this article examines two aspects of arguments concerning harm to the future child: those relating to psychological harms, and those arguing that TT is contrary to the future child’s best interests.3The article examines the moral basis for arguments concerning harm to the future child. It proposes that arguments concerning psychological harm may overlook or minimise the potential benefits flowing from the broader social, familial context into which the child is born. These arguments may be countered, or at least balanced, by considering the future child in this context. In relation to arguments that TT is contrary to the future child’s best interests, the paper examines a non-standard consideration of best interests. It argues that this standard should be used in considering whether or not TT for bone marrow transplant is harmful to the future child, thereby extending moral consideration of interests to intra-familial interests and outcomes. On this basis, it can be argued that TT is not contrary to the interests of the future child. The paper concludes by noting a potential tension between the first guiding principle of the Infertility Treatment Act 1995 (Vic) and the current Victorian policy on TT. (shrink)

The following three points are made. One must consider not only the levels of circulating hormone but the target tissue upon which the hormone acts. Increased testosterone levels alone do not account for differences in displayed intermale aggression, because testosterone and social environment interact in complex ways to influence behavior. A given behavior can be triggered by multiple motivational systems.

The bill to restore federal funding for human fetal tissue research has been passed by the House and awaits Senate approval. But it requires women who are willing to donate fetal tissue to certify that they did not have an abortion with the intent to donate. It further requires researchers to keep the certifications on file and available for government audit. Both requirements spell trouble.

In many animal species, the early development of the embryo follows a stereotypic pattern of cell cleavage, lineage allocation and generation of tissue asymmetry leading to delineation of the body plan with three primary embryonic axes. The mammalian embryo has been regarded as an exception and primary body axes of the mouse embryo were thought to develop after implantation. However, recent findings have challenged this view. Asymmetry in the fertilised oocyte, as defined by the position of the second polar (...) body and the sperm entry point, can be correlated with the orientation of the animal–vegetal and the embryonic–abembryonic axes in the preimplantation blastocyst. Studies of the pattern of morphogenetic movement of cells and genetic activity in the peri‐implantation embryo suggest that the animal–vegetal axis of the blastocyst might presage the orientation of the anterior–posterior axis of the gastrula. This suggests that the asymmetry of the zygote that is established at fertilisation and early cleavage has a lasting impact on the delineation of body axes during embryogenesis. BioEssays 23:508–517, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

Based on a general review of international, representative tissue banking policies that were described in the medical, ethics, and legal literature, this paper reviews the range of standards, both conceptually and in existing regulations, relevant to four main factors:(1) commercialization, (2) confidentiality, (3) informed consent, and (4) quality of research. These four factors were selected as reflective of some of the major ethical considerations that arise in the conduct of tissue banking research. The authors emphasize that any policy (...) or ethical guidelines designed to regulate tissue bank research should address all four factors. Whenever this sort of research is conducted between several institutions or several countries, the paper suggests that the relevant entities work collaboratively to harmonize their standards. (shrink)

Efforts from diverse disciplines, including evolutionary studies and biomechanical experiments, have yielded new insights into the genetic, signaling, and mechanical control of tooth formation and functions. Evidence from fossils and non‐model organisms has revealed that a common set of genes underlie tooth‐forming potential of epithelia, and changes in signaling environments subsequently result in specialized dentitions, maintenance of dental stem cells, and other phenotypic adaptations. In addition to chemical signaling, tissue forces generated through epithelial contraction, differential growth, and skeletal constraints (...) act in parallel to shape the tooth throughout development. Here recent advances in understanding dental development from these studies are reviewed and important gaps that can be filled through continued application of evolutionary and biomechanical approaches are discussed. (shrink)

Neural fetal tissue transplantation offers promise as a treatment for devasting neurologic conditions such as Parkinson's disease. Two types of issues arise from this procedure: those associated with the use of fetuses, and those associated with the use of neural tissue. The former issues have been examined in many forums; the latter have not. This paper reviews issues and arguments raised by the use of fetal tissue in general, but focuses on the implications of the use of (...) neural tissue for basic concepts of personnood and personal identity. (shrink)