Fat Depot–Specific Characteristics Are Retained in Strains Derived From Single Human Preadipocytes

Tchkonia, Tamar; Giorgadze, Nino; Pirtskhalava, Tamar; Thomou, Thomas; DePonte, Matthew; Koo, Ada; Forse, R. Armour; Chinnappan, Dharmaraj; Martin-Ruiz, Carmen; Zglinicki, Thomas von; Kirkland, James L.

doi:10.2337/db06-0540

Cited by 208 publications

(207 citation statements)

References 48 publications

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“…Indeed, intraabdominal/visceral fat accumulation is associated with a higher risk of diabetes and metabolic syndrome, whereas increased s.c. fat in the thighs and hips may even have a protective effect (4,8,26). A growing body of evidence suggests that these depot-specific associations are due to intrinsic differences in the properties of adipocytes in each depot (27,28) and the consequence of a divergence in their developmental origin (1,(9)(10)(11)(12)29). Consistent with this hypothesis, we and others observed high differential expression of developmental genes between intraabdominal and s.c. adipose depots in both rodents and humans (11,12).…”

Section: Discussionsupporting

confidence: 75%

Mesodermal developmental gene Tbx15 impairs adipocyte differentiation and mitochondrial respiration

Gesta

Bézy²,

Mori³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Increased intraabdominal (visceral) fat is associated with a high risk of diabetes and metabolic syndrome. We have previously shown that the mesodermal developmental transcription factor Tbx15 is highly differentially expressed between visceral and subcutaneous (s.c.) fat in both humans and rodents, and in humans visceral fat Tbx15 expression is decreased in obesity. Here we show that, in mice, Tbx15 is 260-fold more highly expressed in s.c. preadipocytes than in epididymal preadipocytes. Overexpression of Tbx15 in 3T3-L1 preadipocytes impairs adipocyte differentiation and decreases triglyceride content. This defect in differentiation can be corrected by stimulating cells with the PPARγ agonist rosiglitazone (Rosi). However, triglyceride accumulation remains decreased by ∼50%, due to a decrease in basal lipogenic rate and increase in basal lipolytic rate. 3T3-L1 preadipocytes overexpressing Tbx15 also have a 15% reduction in mitochondrial mass and a 28% reduction in basal mitochondrial respiration (P = 0.004) and ATP turnover (P = 0.02), and a 45% (P = 0.003) reduction in mitochondrial respiratory capacity. Thus, differential expression of Tbx15 between fat depots plays an important role in the interdepot differences in adipocyte differentiation, triglyceride accumulation, and mitochondrial function that may contribute to the risk of diabetes and metabolic disease.thiazolidinedione | bioenergetics profile | Oil Red O

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Section: Discussionsupporting

confidence: 75%

Mesodermal developmental gene Tbx15 impairs adipocyte differentiation and mitochondrial respiration

Gesta

Bézy²,

Mori³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…It has been shown that regardless of the gender, subcutaneous fat decreases and abdominal fat increases with age (Kuk et al 2009). Elevated visceral fat accumulation is strongly associated with ectopic fat deposition in skeletal muscle, heart, liver, pancreas, or blood vessels, a trend leading to lipotoxicity in aged individuals (Slawik and Vidal-Puig 2006;Tchkonia et al 2010;Tchkonia et al 2006). Nonsubcutaneous fat accumulation is known to be strongly associated with insulin resistance and dyslipidemia (Kuk et al 2009).…”

Section: Adipose Tissue and Obesitymentioning

confidence: 99%

Obesity and related consequences to ageing

Jura

Kozak

2016

AGE

346

203

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Obesity has become a major public health problem. Given the current increase in life expectancy, the prevalence of obesity also raises steadily among older age groups. The increase in life expectancy is often accompanied with additional years of susceptibility to chronic ill health associated with obesity in the elderly. Both obesity and ageing are conditions leading to serious health problems and increased risk for disease and death. Ageing is associated with an increase in abdominal obesity, a major contributor to insulin resistance and the metabolic syndrome. Obesity in the elderly is thus a serious concern and comprehension of the key mechanisms of ageing and age-related diseases has become a necessary matter. Here, we aimed to identify similarities underlying mechanisms related to both obesity and ageing. We bring together evidence that age-related changes in body fat distribution and metabolism might be key factors of a vicious cycle that can accelerate the ageing process and onset of age-related diseases.

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“…Isolation and differentiation of adipocyte precursor cells Human preadipocytes were isolated according to the method of Rodbell [15], with minor modifications, and differentiated for about 30 days in DMEM/F-12 medium supplemented with insulin, dexamethasone, triiodothyronine and rosiglitazone, in line with recently published methods for differentiation of human preadipocytes [16]; for further details on preadipocyte isolation and differentiation, see ESM. Differentiation of cells into adipocytes was assessed through morphological analysis and Oil-Red-O staining.…”

Section: Methodsmentioning

confidence: 99%

Fat depot-related differences in gene expression, adiponectin secretion, and insulin action and signalling in human adipocytes differentiated in vitro from precursor stromal cells

et al. 2007

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Aim/hypothesis The distinct metabolic properties of visceral and subcutaneous adipocytes may be due to inherent characteristics of the cells that are resident in each fat depot. To test this hypothesis, human adipocytes were differentiated in vitro from precursor stromal cells obtained from visceral and subcutaneous fat depots and analysed for genetic, biochemical and metabolic endpoints. Methods Stromal cells were isolated from adipose tissue depots of nondiabetic individuals. mRNA levels of adipocytespecific proteins were determined by real-time RT-PCR.Insulin signalling was evaluated by immunoblotting with specific antibodies. Glucose transport was measured by a 2-deoxy-glucose uptake assay. Adiponectin secretion in the adipocyte-conditioned medium was determined by a specific RIA. Results With cell differentiation, mRNA levels of PPARG, C/EBPα (also known as CEBPA), AP2 (also known as GTF3A), GLUT4 (also known as SLC2A4) were markedly upregulated, whereas GLUT1 (also known as SLC2A1) mRNA did not change. However, expression of C/EBPα, AP2 and adiponectin was higher in subcutaneous than in visceral adipocytes. By contrast, adiponectin was secreted at threefold higher rates by visceral than by subcutaneous adipocytes while visceral adipocytes also showed two-to threefold higher insulin-stimulated glucose uptake. Insulininduced phosphorylation of the insulin receptor, IRS proteins, Akt and extracellular signal-regulated kinase-1/2 was more rapid and tended to decrease at earlier time-points in visceral than in subcutaneous adipocytes. Conclusions/interpretation Subcutaneous and visceral adipocytes, also when differentiated in vitro from precursor stromal cells, retain differences in gene expression, adiponectin secretion, and insulin action and signalling. Thus, the precursor cells that reside in the visceral and subcutaneous fat depots may already possess inherent and specific metabolic characteristics that will be expressed upon completion of the differentiation programme.

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Fat Depot–Specific Characteristics Are Retained in Strains Derived From Single Human Preadipocytes

Cited by 208 publications

References 48 publications

Mesodermal developmental gene Tbx15 impairs adipocyte differentiation and mitochondrial respiration

Mesodermal developmental gene Tbx15 impairs adipocyte differentiation and mitochondrial respiration

Obesity and related consequences to ageing

Fat depot-related differences in gene expression, adiponectin secretion, and insulin action and signalling in human adipocytes differentiated in vitro from precursor stromal cells

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