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Public Health Nutrition Oct 2007The aim was to review and update advances in genetics of obesity. (Review)
Review
OBJECTIVE
The aim was to review and update advances in genetics of obesity.
DESIGN
Analysis and interpretation of recent investigations about regulating the energy balance as well as about gene-nutrient interactions and current nutri-genomic research methods. BACKGROUND AND MAIN STATEMENTS: Obesity results from a long-term positive energy balance. However, its rising prevalence in developed and developing societies must reflect lifestyle changes, since genetic susceptibility remains stable over many generations. Like most complex diseases, obesity derives from a failure of adequate homoeostasis within the physiological system controlling body weight. The identification of genes that are involved in syndromic, monogenic and polygenic obesity has seriously improved our knowledge of body weight regulation. This disorder may arise from a deregulation at the genetic level (e.g. gene transcription or altered protein function) or environmental exposure (e.g. diet, physical activity, etc.).
CONCLUSIONS
In practice, obesity involves the interaction between genetic and environmental factors.
Topics: Adipogenesis; Diet; Energy Metabolism; Genetic Predisposition to Disease; Homeostasis; Humans; Life Style; Nutrigenomics; Obesity; Prevalence
PubMed: 17903322
DOI: 10.1017/S1368980007000626 -
Autophagy Jan 2010Obesity is a direct result of the accumulation of white adipose tissue (WAT). In this study, the role of autophagy in the differentiation of white adipose tissue was... (Review)
Review
Obesity is a direct result of the accumulation of white adipose tissue (WAT). In this study, the role of autophagy in the differentiation of white adipose tissue was studied by deleting the autophagy-related 7 (atg7) gene from adipose tissue in mice. This deletion results in a striking phenotype at the cellular, tissue and whole-organism levels. Adipose tissue deposits in the mutant mice are much smaller in mass than those observed in their wild-type counterparts, and mutant adipocytes exhibit unusual morphological characteristics including multilocular lipid droplets and greatly increased numbers of mitochondria. The knockout mice are noticeably slimmer than their wild-type littermates, despite parity in food and water consumption. The mutant mice also exhibit higher basal physical activity levels and an array of metabolic changes revealed through blood tests. Most importantly, these mice show resistance to high-fat diet-induced obesity and markedly increased sensitivity to insulin. These findings establish a new function for autophagy and provide a new model system for use in the search for treatments for obesity and type II diabetes.
Topics: Adipogenesis; Animals; Autophagy; Diabetes Mellitus, Type 2; Humans; Mice; Models, Biological; Obesity
PubMed: 20110772
DOI: 10.4161/auto.6.1.10814 -
Nature Reviews. Endocrinology Mar 2018Although the major white adipose depots evolved primarily to store energy, secrete hormones and thermo-insulate the body, multiple secondary depots developed additional... (Review)
Review
Although the major white adipose depots evolved primarily to store energy, secrete hormones and thermo-insulate the body, multiple secondary depots developed additional specialized and unconventional functions. Unlike any other fat tissue, dermal white adipose tissue (dWAT) evolved a large repertoire of novel features that are central to skin physiology, which we discuss in this Review. dWAT exists in close proximity to hair follicles, the principal appendages of the skin that periodically grow new hairs. Responding to multiple hair-derived signals, dWAT becomes closely connected to cycling hair follicles and periodically cycles itself. At the onset of new hair growth, hair follicles secrete activators of adipogenesis, while at the end of hair growth, a reduction in the secretion of activators or potentially, an increase in the secretion of inhibitors of adipogenesis, results in fat lipolysis. Hair-driven cycles of dWAT remodelling are uncoupled from size changes in other adipose depots that are controlled instead by systemic metabolic demands. Rich in growth factors, dWAT reciprocally signals to hair follicles, altering the activation state of their stem cells and modulating the pace of hair regrowth. dWAT cells also facilitate skin repair following injury and infection. In response to wounding, adipose progenitors secrete repair-inducing activators, while bacteria-sensing adipocytes produce antimicrobial peptides, thus aiding innate immune responses in the skin.
Topics: Adipocytes, White; Adipogenesis; Adipose Tissue, White; Animals; Energy Metabolism; Hair Follicle; Humans; Mice; Signal Transduction; Subcutaneous Fat
PubMed: 29327704
DOI: 10.1038/nrendo.2017.162 -
Annals of Medicine Mar 2015Evidence from rodents established an important role of brown adipose tissue (BAT) in energy expenditure. Moreover, to sustain thermogenesis, BAT has been shown to be a... (Review)
Review
Evidence from rodents established an important role of brown adipose tissue (BAT) in energy expenditure. Moreover, to sustain thermogenesis, BAT has been shown to be a powerful sink for draining and oxidation of glucose and triglycerides from blood. The potential of BAT activity in protection against obesity and metabolic syndrome is recognized. Recently, an unexpected presence and activity of BAT has been found in adult humans. Here we review the most recent research in this field and, specifically, how new findings apply to humans. Moreover, we seek to clarify the underlying biological processes occurring beyond the burst of new nomenclature in the field. The cell type responsible for thermogenesis, the brown adipocyte, arises from complex developmental processes. In addition to 'classical' brown adipocytes, present in developmentally programmed BAT depots, there are brown adipocytes, named 'brite' (from 'brown-in-white') or 'beige', which appear in response to thermogenic stimuli in white fat due to the so-called 'browning' process. Beige/brite cells appear to be important components of BAT depots in adult humans. In addition to the known control of BAT activity by the sympathetic nervous system, metabolic and hormonal signals originating in muscle or liver (e.g. irisin, FGF21) are recognized as activators of BAT and beige/brite adipocytes.
Topics: Adipocytes, Brown; Adipogenesis; Adipose Tissue, Brown; Animals; Energy Metabolism; Humans; Obesity; Thermogenesis
PubMed: 25230914
DOI: 10.3109/07853890.2014.952328 -
Laboratory Investigation; a Journal of... Oct 2017Obesity is now a major public health problem worldwide. Lifestyle modification to reduce the characteristic excess body adiposity is important in the treatment of... (Review)
Review
Obesity is now a major public health problem worldwide. Lifestyle modification to reduce the characteristic excess body adiposity is important in the treatment of obesity, but effective therapeutic intervention is still needed to control what has become an obesity epidemic. Unfortunately, many anti-obesity drugs have been withdrawn from market due to adverse side effects. Bariatric surgery therefore remains the most effective therapy for severe cases, although such surgery is invasive and researchers continue to seek new control strategies for obesity. Mesenchymal stem cells (MSCs) are a major source of adipocyte generation, and studies have been conducted into the potential roles of MSCs in treating obesity. However, despite significant progress in stem cell research and its potential applications for obesity, adipogenesis is a highly complex process and the molecular mechanisms governing MSC adipogenesis remain ill defined. In particular, successful clinical application of MSCs will require extensive identification and characterization of the transcriptional regulators controlling MSC adipogenesis. Since obesity is associated with the incidence of multiple important comorbidities, an in-depth understanding of the relationship between MSC adipogenesis and the comorbidities of obesity is also necessary to evaluate the potential of effective and safe MSC-based therapies for obesity. In addition, brown adipogenesis is an attractive topic from the viewpoint of therapeutic innovation and future research into MSC-based brown adipogenesis could lead to a novel breakthrough. Ongoing stem cell studies and emerging research fields such as epigenetics are expected to elucidate the complicated mechanisms at play in MSC adipogenesis and develop novel MSC-based therapeutic options for obesity. This review discusses the current understanding of MSCs in adipogenesis and their potential clinical applications for obesity.
Topics: Adipogenesis; Animals; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mice; Obesity; Translational Research, Biomedical
PubMed: 28414326
DOI: 10.1038/labinvest.2017.42 -
Obesity Reviews : An Official Journal... May 2019The bone morphogenetic proteins (BMPs) belong to the same superfamily as related to transforming growth factor β (TGFβ), growth and differentiation factors (GDFs), and... (Review)
Review
The bone morphogenetic proteins (BMPs) belong to the same superfamily as related to transforming growth factor β (TGFβ), growth and differentiation factors (GDFs), and activins. They were initially described as inducers of bone formation but are now known to be involved in morphogenetic activities and cell differentiation throughout the body, including the development of adipose tissue and adipogenic differentiation. BMP4 and BMP7 are the most studied BMPs in adipose tissue, with major roles in white adipogenesis and brown adipogenesis, respectively, but other BMPs such as BMP2, BMP6, and BMP8b as well as some inhibitors and modulators have been shown to also affect adipogenesis. It has become ever more important to understand adipose regulation, including the BMP pathways, in light of the strong links between obesity and metabolic and cardiovascular disease. In this review, we summarize the available information on BMP signaling in adipose tissue using preferentially articles that have appeared in the last decade, which together demonstrate the importance of BMP signaling in adipose biology.
Topics: Adipogenesis; Adipose Tissue; Animals; Bone Morphogenetic Proteins; Humans; Signal Transduction
PubMed: 30609449
DOI: 10.1111/obr.12822 -
Canadian Journal of Gastroenterology &... 2020Vitamin D has been discovered centuries ago, and current studies have focused on the biological effects of vitamin D on adipogenesis. Besides its role in calcium... (Review)
Review
Vitamin D has been discovered centuries ago, and current studies have focused on the biological effects of vitamin D on adipogenesis. Besides its role in calcium homeostasis and energy metabolism, vitamin D is also involved in the regulation of development and process of metabolic disorders. Adipose tissue is a major storage depot of vitamin D. This review summarized studies on the relationship between vitamin D and adipogenesis and furthermore focuses on adipose metabolic disorders. We reviewed the biological roles and functionalities of vitamin D, the correlation between vitamin D and adipose tissue, the effect of vitamin D on adipogenesis, and adipose metabolic diseases. Vitamin D is associated with adipogenesis, and vitamin D supplements can reduce the burden caused by metabolic diseases. The review provides new insights and basis for medical therapy on adipose metabolic diseases.
Topics: Adipogenesis; Adipose Tissue; Animals; Humans; Metabolic Diseases; Vitamin D
PubMed: 32149047
DOI: 10.1155/2020/2656321 -
ELife Aug 2023Delta-like homolog 1 (), an inhibitor of adipogenesis, controls the cell fate of adipocyte progenitors. Experimental data presented here identify two independent...
Delta-like homolog 1 (), an inhibitor of adipogenesis, controls the cell fate of adipocyte progenitors. Experimental data presented here identify two independent regulatory mechanisms, transcriptional and translational, by which (TIS7) and its orthologue (SKMc15) regulate levels. Mice deficient in both and (dKO) had severely reduced adipose tissue and were resistant to high-fat diet-induced obesity. Wnt signaling, a negative regulator of adipocyte differentiation, was significantly upregulated in dKO mice. Elevated levels of the Wnt/β-catenin target protein Dlk1 inhibited the expression of adipogenesis regulators and , and fatty acid transporter . Although both and contributed to this phenotype, they utilized two different mechanisms. acted by controlling Wnt signaling and thereby transcriptional regulation of . On the other hand, distinctive experimental evidence showed that Ifrd2 acts as a general translational inhibitor significantly affecting Dlk1 protein levels. Novel mechanisms of regulation in adipocyte differentiation involving and are based on experimental data presented here.
Topics: Animals; Mice; Adipocytes; Adipogenesis; Adipose Tissue; Calcium-Binding Proteins; CD36 Antigens; Cell Differentiation; Immediate-Early Proteins; Membrane Proteins
PubMed: 37603466
DOI: 10.7554/eLife.88350 -
ELife Mar 2023In mammals, interactions between the bone marrow (BM) stroma and hematopoietic progenitors contribute to bone-BM homeostasis. Perinatal bone growth and ossification...
In mammals, interactions between the bone marrow (BM) stroma and hematopoietic progenitors contribute to bone-BM homeostasis. Perinatal bone growth and ossification provide a microenvironment for the transition to definitive hematopoiesis; however, mechanisms and interactions orchestrating the development of skeletal and hematopoietic systems remain largely unknown. Here, we establish intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) modification as a posttranslational switch that dictates the differentiation fate and niche function of early BM stromal cells (BMSCs). By modifying and activating RUNX2, O-GlcNAcylation promotes osteogenic differentiation of BMSCs and stromal IL-7 expression to support lymphopoiesis. In contrast, C/EBPβ-dependent marrow adipogenesis and expression of myelopoietic stem cell factor (SCF) is inhibited by O-GlcNAcylation. Ablating O-GlcNAc transferase (OGT) in BMSCs leads to impaired bone formation, increased marrow adiposity, as well as defective B-cell lymphopoiesis and myeloid overproduction in mice. Thus, the balance of osteogenic and adipogenic differentiation of BMSCs is determined by reciprocal O-GlcNAc regulation of transcription factors, which simultaneously shapes the hematopoietic niche.
Topics: Mice; Animals; Bone Marrow; Glycosylation; Osteogenesis; Cell Differentiation; Adipogenesis; Bone Marrow Cells; Mammals
PubMed: 36861967
DOI: 10.7554/eLife.85464 -
PLoS Genetics Sep 2022Transcriptional elongation is a universal and critical step during gene expression. The super elongation complex (SEC) regulates the rapid transcriptional induction by...
Transcriptional elongation is a universal and critical step during gene expression. The super elongation complex (SEC) regulates the rapid transcriptional induction by mobilizing paused RNA polymerase II (Pol II). Dysregulation of SEC is closely associated with human diseases. However, the physiological role of SEC during development and homeostasis remains largely unexplored. Here we studied the function of SEC in adipogenesis by manipulating an essential scaffold protein AF4/FMR2 family member 4 (AFF4), which assembles and stabilizes SEC. Knockdown of AFF4 in human mesenchymal stem cells (hMSCs) and mouse 3T3-L1 preadipocytes inhibits cellular adipogenic differentiation. Overexpression of AFF4 enhances adipogenesis and ectopic adipose tissue formation. We further generate Fabp4-cre driven adipose-specific Aff4 knockout mice and find that AFF4 deficiency impedes adipocyte development and white fat depot formation. Mechanistically, we discover AFF4 regulates autophagy during adipogenesis. AFF4 directly binds to autophagy-related protein ATG5 and ATG16L1, and promotes their transcription. Depleting ATG5 or ATG16L1 abrogates adipogenesis in AFF4-overepressing cells, while overexpression of ATG5 and ATG16L1 rescues the impaired adipogenesis in Aff4-knockout cells. Collectively, our results unveil the functional importance of AFF4 in regulating autophagy and adipogenic differentiation, which broaden our understanding of the transcriptional regulation of adipogenesis.
Topics: Adipogenesis; Animals; Autophagy; Autophagy-Related Proteins; Cell Differentiation; Humans; Mice; RNA Polymerase II; Transcription Factors; Transcriptional Elongation Factors
PubMed: 36149892
DOI: 10.1371/journal.pgen.1010425