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

Abstract

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.

The impact of obesity on secretion of adiponectin multimeric isoforms differs in visceral and subcutaneous adipose tissue

“…Consistent with our data, the study by Drolet et al 12 showed no difference in total adiponectin secretion between subcutaneous and omental adipocytes in subjects with a wide range of BMI, with an exception of a subgroup of visceral obese who presented lower omental cell adiponectin release when compared with subcutaneous cells. Motoshima et al 11 and Perrini et al 3 reported that the cultured human omental adipocytes secrete more adiponectin than subcutaneous adipocytes and that its secretion is inversely correlated to BMI, whereas the secretion from the subcutaneous cells was unrelated to BMI. Contrary to this, Phillips et al 29 showed lower adiponectin levels secreted by VAT than SAT explants of obese as well as type 2 diabetic people.…”

Adipose Tissue: A Metabolic Regulator. Potential Implications for the Metabolic Outcome of Subjects Born Small for Gestational Age (SGA)

“…Even in adipocytes differentiated in vitro from precursor mesenchymal cells, adiponectin expression is lower in visceral adipocytes than subcutaneous adipocytes [56].…”

Gluteofemoral body fat as a determinant of metabolic health

“…[6][7][8] The particular importance of visceral fat accumulation versus subcutaneous fat depot dysfunction has recently been challenged 9,10 as there is mounting evidence to support that visceral adipocytes are phenotypically different from subcutaneous adipocytes. 11 Nevertheless, it is the protective role of lower body, that is, gluteofemoral fat that is striking. The protective properties of the lower-body fat depot have been confirmed in many studies conducted in subjects with a wide range of age, BMI and co-morbidities (Table 1).…”

“…Differences in expression of adipokine genes and in secretion in vitro are well established when comparing subcutaneous and visceral fat. 11,58 However, little is known regarding differences between upper-and lower-body fat.…”