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Adipocyte turnover relevance to human adipose tissue morphology

The relation between adipose tissue morphology and adipocyte turnover was determined in 35 subjects who were previously investigated and who were not part of the methodological study. The studies were approved by the regional ethics committee and explained in detail to each subject Adipocyte Turnover: Relevance to Human Adipose Tissue Morphology Erik Arner,1 Pål O. Westermark,2 Kirsty L. Spalding,3 Tom Britton,4 Mikael Ryde´n,1 Jonas Frise´n,3 Samuel Bernard,5 and Peter Arner1 OBJECTIVE—Adipose tissue may contain few large adipocytes (hypertrophy) or many small adipocytes (hyperplasia). We inves Adipose tissue morphology correlates with insulin measures and is linked to the total adipocyte number independently of sex and body fat level. Low generation rates of adipocytes associate with.

OBJECTIVE-Adipose tissue may contain few large adipocytes (hypertrophy) or many small adipocytes (hyperplasia). We investigated factors of putative importance for adipose tissue morphology. RESEARC. Total adipocyte number and morphology were negatively related (r = -0.66); i.e., the total adipocyte number was greatest in pronounced hyperplasia and smallest in pronounced hypertrophy. The absolute number of new adipocytes generated each year was 70% lower (P < 0.001) in hypertrophy than in hyperplasia, and individual values for adipocyte generation and morphology were strongly related (r = 0.7, P < 0.001) OBJECTIVE: Adipose tissue may contain few large adipocytes (hypertrophy) or many small adipocytes (hyperplasia). We investigated factors of putative importance for adipose tissue morphology. RESEARCH DESIGN AND METHODS: Subcutaneous adipocyte size and total fat mass were compared in 764 subjects with BMI 18-60 kg/m(2). A morphology value was defined as the difference between the measured.

Adipocyte Turnover: Relevance to Human Adipose Tissue

  1. Human adipose tissue morphology and function Relation to insulin sensitivity and glucose tolerance with focus on pregnancy and women with previous Keywords: Adipose tissue, adipocyte, adipokines, insulin resistance, pregnancy, gestational diabetes mellitus, type 2 diabetes mellitus
  2. White adipose tissue (WAT) can develop into several phenotypes with different pathophysiological impact on type 2 diabetes. To better understand the adipogenic process, the transcriptional events that occur during in vitro differentiation of human adipocytes were investigated and the findings linked to WAT phenotypes
  3. Adipocyte Turnover: Relevance to Human Adipose Tissue Morphology By Erik Arner, Pål O. Westermark, Kirsty L. Spalding, Tom Britton, Mikael Rydén, Jonas Frisén, Samuel Bernard and Peter Arner Topics: Original Articl

Adipocyte turnover: relevance to human adipose tissue morphology. Diabetes. (P < 0.001) in hypertrophy than in hyperplasia, and individual values for adipocyte generation and morphology were strongly related (r = 0.7, P < 0.001). The relative death rate (approximately 10% per year) or mean age of adipocytes. Adipose morphology is defined as the number and size distribution of adipocytes (fat cells) within adipose tissue. Adipose tissue with fewer but larger adipocytes is said to have a 'hypertrophic' morphology, whereas adipose with many adipocytes of a smaller size is said to have a 'hyperplastic' morphology. Hypertrophic adipose morphology is positively associated with insulin resistance, diabetes and cardiovascular disease Arner, E. et al. Adipocyte turnover: Relevance to human adipose tissue morphology. Diabetes 59 , 105-109 (2010). CAS PubMed Article Google Schola Adipocyte Turnover: Relevance to Human Adipose Tissue Morphology. Overview of attention for article published in Diabetes, October 2009. Adipocyte Turnover: Relevance to Human Adipose Tissue Morphology Published in: Diabetes, October 2009 DOI: 10.2337/db09-0942: Pubmed ID: 19846802 White adipose tissue is a highly plastic organ and is an important regulator of whole-body metabolism and energy balance. The magnitude of adipose tissue mass is determined by dynamic changes in the synthesis and breakdown (i.e. turnover) of adipocytes and triacylglycerols (TGs). Obesity is a disorder characterised by excessive adiposity and is a risk factor for diseases, including the.

We are not allowed to display external PDFs yet. You will be redirected to the full text document in the repository in a few seconds, if not click here.click here Adipocyte turnover is not only important for regulating the total fat mass but also for the morphology of human adipose tissue. Using the carbon-14 dating method (5) we recently found that adipocyte turnover is important for the development of hyperplasia and hypertrophy

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White adipose tissue (WAT) dysfunction is a hallmark of obesity and associated metabolic complications such as type 2 diabetes (T2D) [1]. WAT expands by increasing adipocyte number (hyperplasia) and size (hypertrophy). Their relative importance differs between individuals resulting in alternate adipose morphologies For instance, white adipose tissue (WAT) can expand its volume by 10 times under an obese state through hypertrophy (enlarged adipocyte size) and hyperplasia (increased adipocyte number), whereas it rapidly shrinks by lipolysis upon fasting or cold exposure, thereby supplying fatty acids to peripheral organs (1) [2] Adipocyte turnover:relevance to human adiopose tissue morphology- Arner E et al, Diabetes, 2010,59(1):105-9. PMID:19846802 [8] Cawthorn WP, Scheller EL, MacDougald OA., Adipose tissue stem cells meet preadipocyte commitment: going back to the future. J Lipid Res. 2012 Feb;53(2):227-46 White adipose tissue hypertrophy (fewer but larger adipocytes) is associated with increased adipose inflammation, lipolysis, insulin resistance, and diabetes risk. Gao et al. use a combination of clinical and mouse studies to identify the adipocyte-expressed transcription factor EBF1 as a regulator of adipocyte morphology and lipolysis Arner, E. et al. Adipocyte turnover: relevance to human adipose tissue morphology. Diabetes 59 , 105-109 (2010). CAS PubMed Google Schola

Request PDF | [Localization of adipose tissue: clinical implications] | The excessive accumulation of the adipose tissue is at the origin of the obesity. However its severity has no direct. Changes in white adipose tissue mass and cellularity are linked to type 2 diabetes. • Adipocyte hypertrophy associates with insulin resistance and type 2 diabetes. • Altered lipid turnover predicts obesity and type 2 diabetes development. • Targeting white adipose tissue therapeutically is challenging but possible

E. Arner, P. O. Westermark, K. L. Spalding, et al., Adipocyte Turnover Relevance to Human Adipose Tissue morphology, Diabetes, Vol. 59, No. 1, 2010, pp. 105-109. Adipocyte turnover: Relevance. to human adipose tissue morphology. in mammary adipose tissue of human breast tissue in cases with and without breast cancer In the present study, adipocyte DMS associated with adipose hypertrophy display strong overlap with those observed in T2D further strengthening the causality between adipose morphology and diabetes. The measure of adipose morphology applied herein is adjusted for, and thus not related to, total body fat [23]

Arner, E. et al. Adipocyte turnover: relevance to human adipose tissue morphology. Diabetes 59 , 105-109 (2010). CAS PubMed Google Schola Emerging evidence highlights that dysfunction of adipose tissue contributes to impaired insulin sensitivity and systemic metabolic deterioration in obese state. Of note, adipocyte hypertrophy serves as a critical event which associates closely with adipose dysfunction. An increase in cell size exacerbates hypoxia and inflammation as well as excessive collagen deposition, finally leading to.

  1. White adipose tissue (WAT) morphology characterized by hypertrophy (i.e., fewer but larger adipocytes) associates with increased adipose inflammation, lipolysis, insulin resistance, and risk of diabetes. However, the causal relationships and the mechanisms controlling WAT morphology are unclear. Herein, we identified EBF1 as an adipocyte-expressed transcription factor with decreased expression.
  2. Functionally discrete adipocyte populations are also present within individual adipose tissue depots (16 - 19). Varlamov et al. reported striking heterogeneity in free fatty acid and glucose uptake by white adipocytes in adipose tissue explants from Rhesus macaques and fatty acid uptake by in‐vitro‐differentiated human adipocytes
  3. Arner E, et al. Adipocyte turnover: relevance to human adipose tissue morphology. Diabetes . 2010;59(1):105-109. View this article via: PubMed CrossRef Google Schola
  4. Marrow adipose tissue expands in states of low bone density but additionally expands in the setting of obesity. Marrow adipose tissue response to exercise approximates that of WAT. Exercise reduces both adipocyte size as well as marrow adipose tissue volume, as quantified by MRI or μCT imaging of bone stained with the lipid binder osmium.
  5. Adipose tissue fibrosis is decreased in DM subjects with obesity. (A) Sirius Red staining of human adipose tissue. Left: Quantified age‐adjusted Sirius Red staining; ordinate: Sirius Red staining intensity, arbitrary intensity units (A.U.); *P < 0.005 comparing DM and NDM groups
  6. Raajendiran et al. report the identification of three adipocyte progenitor cell (APC) subtypes that reside in human adipose tissues. These APCs have distinct molecular phenotypes yet retain similar adipogenic potential. The APCs give rise to adipocytes with divergent metabolic and endocrine capacities and their distribution varies in type 2 diabetes patients

Adipocyte Turnover : Relevance to Human Adipose Tissue

Arner, E., Westermark, P., Spalding, K.L., Britton, T., Ryden, M., Frisen, J., Bernard, S. and Arner, P. (2010) Adipocyte Turnover Relevance to Human Adipose Tissue. Arner's group demonstrated that the adipocyte morphology index was highly related to in vivo adipocyte turnover, as measured by the DNA incorporation of 14 C. To the best of our knowledge, to date, no study has directly assessed the relationship between quantitative measures of in vivo adipose cell kinetics and markers of metabolic health in humans Adipocyte turnover: relevance to human adipose tissue morphology. (2011). Adipose tissue fat cell size and number in relation to metabolism in randomly selected middle-aged men and women. Body fat distribution, adipocyte size, and metabolic characteristics of nondiabetic adults. Central role of the adipocyte in the metabolic syndrome. (1997) Adipose tissue dysfunction is a major pathogenic determinant of obesity and related metabolic disorders. Although DNA methylation is one of the crucial epigenetic modifications in adipocytes, the molecular determinant and its roles in maintaining adipocyte function remain elusive. Here, we show that DNA methylation directs distal enhancer-mediated transcriptomic features of adipocytes In human adipose tissue, decreased adipocyte size is detected in regions with fibrosis as compared with fibrosis-free cells . The development of a prototypic tool (AdipoScan) based on elastography shows that adipose tissue fibrosis is associated with significant change in tissue stiffness

(2009). Adipocyte size predicts incidence of type 2 diabetes in women. Adipocyte turnover: relevance to human adipose tissue morphology. (2006). Adiponectin receptors in human adipose tissue: effects of obesity, weight loss, and fat depots. (2004). Adipose tissue as an endocrine organ. (2007) LB S, GA B, SW C, E D, JA G. Glucose metabolism and the response to insulin by human adipose tissue in spontaneous and Britton T, Ryden M, Frisen J, et al. Adipocyte Turnover: Relevance to Human Adipose Tissue Morphology. Diabetes. 2009;591:105-9 Thematic review series: Adipocyte Biology.Sympathetic and sensory innervation.

Transcriptional Dynamics During Human Adipogenesis and Its

Background The adipose tissue is important for development of insulin resistance and type 2 diabetes and adipose tissue dysfunction has been proposed as an underlying cause. In the present study we investigated presence of adipocyte hypertrophy, and gene expression pattern of adipose tissue dysfunction in the subcutaneous adipose tissue of healthy, non-obese subjects predisposed to type 2. Adipose tissue morphology is an important predictor of adipose tissue function that is tightly controlled by a constant turnover of fat cells (17, 18). Subjects with few large adipocytes (adipose hypertrophy) have a lower turnover rate than those with many small fat cells (adipose hyperplasia), and hypertrophy associates with a metabolically more unfavorable profile ( 18 ) [2] Adipocyte turnover:relevance to human adiopose tissue morphology- Arner E et al, Diabetes, 2010,59(1):105-9. PMID:19846802 Primary preadipocyte isolation and differentiation [3] van Harmelen V, Skurk T, Hauner H (2005) Primary culture and differentiation of human adipocyte precursor cells. Methods Mol Med 107:125-13

Adipose morphology is defined as the number and size distribution of adipocytes (fat cells) within adipose tissue. Adipose tissue with fewer but larger adipocytes is said to hav Adipose tissue (AT) is now well recognized as an endocrine organ involved in energy homeostasis regulation acting both on the central nervous system and at the local level via its hormonal secretion such as leptin. Recently, the abdominal subcutaneous AT, which is easily accessible by using several procedures, became one of the important parameters used to phenotype morbidly obese patients Adipose morphology is defined as the number and size distribution of adipocytes (fat cells) within adipose tissue. Adipose tissue with fewer but larger adipocytes is said to have a 'hypertrophic' morphology, whereas adipose with many adipocytes of a smaller size is said to have a 'hyperplastic' morphology. Hypertrophic adipose morphology is positively associated with insulin resistance. Adipocyte Turnover: Relevance to Human Adipose Tissue Morphology Adipocyte Turnover: Relevance to Human Adipose Tissue Morphology Depot-specific differences in perilipin and hormone-sensitive lipase..

Adipose tissue-derived stem cells (ADSCs) are pluripotent mesenchymal stem cells found in relatively high percentages in the adipose tissue and able to self-renew and differentiate into many different types of cells. Extracellular vesicles (EVs), small membrane vesicular structures released during cell activation, senescence, or apoptosis, act as mediators for long distance communication. Obesity contributes to Type 2 diabetes by promoting systemic insulin resistance. Obesity causes features of metabolic dysfunction in the adipose tissue that may contribute to later impairments of insulin action in skeletal muscle and liver; these include reduced insulin-stimulated glucose transport, reduced expression of GLUT4, altered expression of adipokines, and adipocyte hypertrophy (7) Arner E, Westermark PO, Spalding KL, Britton T, Ryden M, Frisen J, et al. Adipocyte Turnover: Relevance to Human Adipose Tissue Morphology. Diabetes. 2009;59(1):105-9. (8) Kunath A, Klöting N. Adipocyte biology and obesity-mediated adipose tissue remodeling Background: Adipose tissue must expand in response to excess caloric intake.Results: Insulin-like growth factor-binding protein 4 (IGFbp4) expression negatively correlates with adipose tissue growth. Insulin and IGF-1 stimulate and IGFbp4 suppresses adipose tissue expansion in an ex vivo explant model.Conclusion: IGF-1/IGFbp4 signaling controls post-developmental adipose tissue expansion. This review summarizes current knowledge on the biological relevance of carotenoids and some of their metabolites in obesity management. The relationship between carotenoids and obesity is considered in clinical studies and in preclinical studies. Adipose tissue is a key organ in obesity etiology and the main storage site for carotenoids. We thus first describe carotenoid metabolism in.

Adipose morphology and metabolic disease Journal of

Numerous studies have revealed various aspects of adipose tissue (AT) and adipocyte dysfunction in the pathophysiology of Limiting the excess fat cell enlargement that leads to detrimental morphology could prevent some of Britton T., Ryden M., Frisen J., and al. Adipocyte turnover: relevance to human adipose tissue morphology Diabetes. OBJECTIVE Although long-term weight regain may occur after bariatric surgery, many patients are protected against relapse or development of type 2 diabetes. The study objective was to investigate whether this involves beneficial changes in adipose function. RESEARCH DESIGN AND METHODS Forty-nine obese women were investigated before and 2 and 5 years after Roux-en-Y gastric bypass (RYGB) The marrow adipose tissue depot is poorly understood in terms of its physiologic function and relevance to bone health. Marrow adipose tissue expands in states of low bone density but additionally expands in the setting of obesity;. Marrow adipose tissue response to exercise approximates that of WAT exercise reduces both adipocyte size as well.

Enlarged adipocytes from subcutaneous vs

  1. Adipose tissue dysregulation and metabolic consequences in childhood and adolescent obesity: Biochemical and molecular roles of nutrients Perilla oil prevents the excessive growth of visceral adipose tissue in rats by down-regulating adipocyte differentiation 1, 2. (2010) Adipocyte turnover: relevance to human adipose tissue morphology
  2. ed only women with morbid obesity. Thus, 9. Arner E, Westermark PO, Spalding KL et al (2010) Adipocyte the impact of regional fat cell size in men and in women turnover: relevance to human adipose tissue morphology
  3. ant deter
  4. Arner E, Westermark PO, Spalding KL, Britton T, Ryden M, Frisen J, et al. Adipocyte turnover: relevance to human adipose tissue morphology. Diabetes. 2010;59:105-9. CAS Article PubMed Google Scholar 5. Arner E, Ryden M, Arner P. Tumor necrosis factor alpha and regulation of adipose tissue
  5. e depot-specific PGE 2 and PGF 2 α release and mRNA expression of enzymes or receptors involved in PG synthesis or signaling in human adipose tissues; (2) to identify changes in expression of these transcripts through preadipocyte differentiation; and (3) to exa
  6. Regulation of stem cell differentiation in adipose tissue by chronic inflammation Regulation of stem cell differentiation in adipose tissue by chronic inflammation Ye, Jianping; Gimble, Jeffery M 2011-12-01 00:00:00 1. Recent studies suggest that a local hypoxic response leads to chronic inflammation in the adipose tissue of obese individuals
  7. Article Adipocyte Turnover: Relevance to Human Adipose Tissue Morphology Detailed information of the J-GLOBAL is a service based on the concept of Linking, Expanding, and Sparking, linking science and technology information which hitherto stood alone to support the generation of ideas. By linking the information entered, we provide opportunities to make unexpected discoveries and obtain.

Altmetric - Adipocyte Turnover: Relevance to Human Adipose

The study of adipocyte turnover (Fig. 3 in main text) was conducted on a separate group of subjects who had previously been investigated (4). The turnover data were re-calculated and set in relation to adipose tissue morphology as described in the main text. These studies required very large amounts of adipose tissue (>100 g, preferably about. Furthermore, adipose hypertrophy confers an increased risk for the development of type 2 diabetes (Lö nn et al., 2010;Weyer et al., 2000).Although human adipocyte turnover (i.e., adipocyte birth/death rate) is significantly reduced in adipose hypertrophy (Arner et al., 2010b), the mechanisms promoting differences in adipose morphology are still largely unknown

Dynamics of adipose tissue turnover in human metabolic

mechanisms that determine human body fat pattern-ing, and which link adipocyte biology, body fat distri-bution and metabolic disease risk, remain poorly understood. This has led to a growing need to estab-lish suitable in vitro models to facilitate the investiga-tion of regional adipocyte biology. White adipose tissue (WAT) has traditionally bee We compared native adipose tissue with primary human adipocyte cultures and have also included expression levels for the mature adipocyte markers FABP4 (aP2) and ADIPOQ (adiponectin), the white adipocyte lineage marker HOXC9, and genes characteristically expressed in thermogenic brown or brite adipocytes (PPARGC1A, CPT1B, FABP3, and UCP1), as these provide important information regarding the. Adipocyte turnover: relevance to human adipose tissue morphology E Arner, PO Westermark, KL Spalding, T Britton, M Rydén, J Frisén, Diabetes 59 (1), 105-109 , 201 Analysis of their adipose tissue morphology revealed increases in both adipocyte size and number in most depots. Reintroduction of an ordinary chow diet [12] to such animals precipitated a period of weight loss during which only mean adipocyte size returned to normal Specific bio-active dietary compounds modulate numerous metabolic processes in adipose tissue (AT), including pre-adipocyte proliferation and differentiation. AT dysfunction, rather than an increased fat mass per se, is strongly associated with the development of insulin resistance and is characterized by impaired adipogenesis, hypertrophic adipocytes, inflammation, and impairments in.

ANAT2241 Connective Tissue Components - Embryology

Fat cell turnover in humans - ScienceDirec

Adipocyte turnover: relevance to human adipose tissue morphology. Diabetes 59: 105-109, 2010. doi: 10.2337/db09-0942. Crossref | PubMed | ISI Google Scholar; 15. Arner P, Arner E, Hammarstedt A, Smith U. Genetic predisposition for Type 2 diabetes, but not for overweight/obesity, is associated with a restricted adipogenesis Analysis of their adipose tissue morphology revealed increases in both adipocyte size and number in most depots. Reintroduction of an ordinary chow diet [ clarification needed ] to such animals precipitated a period of weight loss during which only mean adipocyte size returned to normal

Body fat accumulation, distribution and metabolic activity are factors in the pathophysiology of obesity and type 2 diabetes (T2D). We investigated adipose blood flow, fatty acid uptake (FAU), and. Adipose tissue morphology and expression of various genes / proteins including collagens and caveolin-1 was examined. Glucose, insulin, fasting and fed free fatty acids were measured in serum. SNTB2 expression was determined in adipose tissues of patients. Results: Upon high fat diet SNTB2-/-mice displayed reduced adiposity and adipocyte. Under obese conditions, adipose tissue can become oxygen-deficient or hypoxic. Extensive work has been done using various diet-induced obesity models to demonstrate an important role of hypoxia-induced signaling in adipose tissue and its impact on adipose functions related to adipogenesis, insulin sensitivity, and inflammation. We have recently identified a new mechanism connecting activation. Adipose tissue, body fat, or simply fat is a loose connective tissue composed mostly of adipocytes. In addition to adipocytes, adipose tissue contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, vascular endothelial cells and a variety of immune cells such as adipose tissue macrophages.Adipose tissue is derived from preadipocytes 8 Adipose Tissue and Skeletal Muscle Plasticity in Obesity and Metabolic Disease Jozef Ukropec 1 and Barbara Ukropcova 1,2 1Institute of Experimental Endocrin ology Slovak Academy of Sciences, 2Institute of Pathological Physiology, Faculty of Medicine Comenius U niversity, Slovakia 1. Introduction Obesity and lack of physical activity are two major factors contributing considerably to th

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Adipose stem cells, which reside in a vascular niche, are essential to the development and maintenance of adipose tissue. Data from humans and rodents show that maintenance of adult adipose tissue is a dynamic process. Adipocyte turnover in young adult mice is estimated to be greater than 10% per month. The adipose stem cell niche is just a Large mammals are capable of thermoregulation shortly after birth due to the presence of brown adipose tissue (BAT). The majority of BAT disappears after birth and is replaced by white adipose tissue (WAT). We analyzed the postnatal transformation of adipose in sheep with a time course study of the perirenal adipose depot. We observed changes in tissue morphology, gene expression and.

Epigenetic regulation of diabetogenic adipose morpholog

The epigenetic regulation of adipose tissue plasticity PNA

Furthermore, the number and proliferative capacity of WAT lineage‐specific precursors in the adipose tissue stroma of adipocyte Atg7 knockout mice are not altered (Singh et al. 2009). One interpretation is that the absence of autophagy forces committed WAT lineage precursor cells to transdifferentiate into a BAT‐like phenotype Tenomodulin promotes human adipocyte differentiation and beneficial visceral adipose tissue expansion Academic research paper on Biological sciences 0. 0. Share paper. Overexpressing the novel autocrine/endocrine adipokine WISP2 induces hyperplasia of the heart, white and brown adipose tissues and prevents insulin resistance

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MSC to adipocyte (human) - resource_browse

White fat in mice can be forced to burn energy like brownANAT2241 Connective Tissue Types - EmbryologyCold-Activated Brown Adipose Tissue in Healthy Men | NEJMPathology Outlines - Angiolipoma

Preadipocyte to adipocyte - resource_browse

Brown adipose tissue is present mostly in the fetus and in young children, and its main purpose is thermogenesis. Small deposits of brown adipose tissue persist into adult life. White adipose tissue is the major adipose tissue in adults, and it plays a role in several disease states, most notably obesity, metabolic syndrome, and type 2 diabetes 51 FRACTAL CHARACTERISTICS OF ADIPOCYTE DYNAMICS IN MICE Elvira GUBCEAC1, Liviu GAITA1, Paul GAGNIUC2-4, Manuella MILITARU1 1University of Agronomic Sciences and Veterinary Medicine, Bucharest, Romania 2National Institute of Diabetes, Nutrition and Metabolic Diseases N.C. Paulescu, Bucharest, Romania 3National Institute of Pathology Victor Babes, Romani

Early B Cell Factor 1 Regulates Adipocyte Morphology and

Cellularity of adipose tissue in domesticated animals varies not only with species, sex, age and management conditions but also with depot. Differences in depots are important in animal production because of the economic and welfare implications and in humans in relation to obesity. The final amount of fat and its composition depends on the differentiation of mesenchymal multipotent precursor. Department of Human Biology Maastricht University Medical Centre The Netherlands Adipogenesis and adipocyte turnover in adipose tissue.. 22 2.4.2. Lipogenesis and lipolysis acquired obesity affects adipose tissue and adipocyte function and how these link to whole bod This chapter provides an overview of the development and function of white adipose tissue, with a focus on infancy, childhood, and adolescence. First, we describe the development and growth of..

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