Insulin acutely regulates the expression of the peroxisome proliferator-activated receptor-gamma in human adipocytes.

Abstract

Peroxisome proliferator-activated receptor (PPAR)-gamma is one of the key actors of adipocyte differentiation. This study demonstrates 1) that PPAR-gamma mRNA expression is not altered in subcutaneous adipose tissue (n = 44) or in skeletal muscle (n = 19) of subjects spanning a wide range of BMIs (20-53 kg/m2) and 2) that insulin acutely increases PPAR-gamma mRNA expression in human adipocytes both in vivo and in vitro. The effect of insulin was investigated in abdominal subcutaneous biopsies obtained before and at the end of a 3-h euglycemic-hyperinsulinemic clamp. Insulin significantly increased PPAR-gamma mRNA levels in lean subjects (88 +/- 17%, n = 6), in type 2 diabetic patients (100 +/- 19%, n = 6), and in nondiabetic obese patients (91 +/- 20%, n = 6). Both PPAR-gamma1 and PPAR-gamma2 mRNA variants were increased (P < 0.05) after insulin infusion. In isolated human adipocytes, insulin induced the two PPAR-gamma mRNAs in a dose-dependent manner, with half-maximal stimulation at a concentration of approximately 1-5 nmol/l. However, PPAR-gamma2 mRNA was rapidly (2 h) and transiently increased, whereas a slow and more progressive induction of PPAR-gamma1 was observed during the 6 h of incubation. In explants of human adipose tissue, PPAR-gamma protein levels were significantly increased (42 +/- 3%, P < 0.05) after 12 h of incubation with insulin. These data demonstrate that PPAR-gamma belongs to the list of the insulin-regulated genes and that obesity and type 2 diabetes are not associated with alteration in the expression of this nuclear receptor in adipose tissue.

PPARγ activity in subcutaneous abdominal fat tissue and fat mass gain during short-term overfeeding

“…Changes in plasma insulin tended to be related to fat mass gain. This effect of short-term overfeeding was in accordance with the observed increase in PPARg mRNA levels in subcutaneous abdominal fat tissue after a 3 h insulin infusion 20 and the induction of PPARg mRNA in isolated human adipocytes by insulin. 3 The weight gain period in this study was 2 weeks and the extent of induction of PPARg expression was positively related to fat gain over this interval.…”

“…The study enclosed a 7-day baseline period (days 1-8) and a 14-day overfeeding period (days [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. During the baseline period subjects chose their diets from a variety of food items provided daily in weighed food packages, bringing back the leftovers the next day, for calculation of habitual energy intake.…”

PPARs and adipocyte function

“…Accordingly, its expression is highest post-prandially and is down-regulated by fasting consistent with the stimulatory effect of insulin on PPAR expression [42,43]. In the context of a high-fat diet, docking protein 1 (DOK1)-mediated insulin signalling also enhances PPAR activity by counteracting the inhibitory effect of extra-cellular signal-regulated kinase (ERK)-mediated PPAR phosphorylation (thereby promoting adipocyte hypertrophy).…”

Obesity and polymorphisms in genes regulating human adipose tissue

“…23 BMI has been reported to increase, or to have no impact on, PPARG expression in subcutaneous adipose tissue. [23][24][25] A common coding gene variant, Pro12A-la located in the 5 0 -region specific for PPARG2, is according to a meta-analysis of 40 data sets comprising approximately 19 000 subjects associated with higher BMI in the overweight and obese subset (BMI427 kg/m 2 ). 26 The disparate effects of the Pro12Ala polymorphism on BMI in obese and lean individuals suggest that this genetic variant interacts with other factors, which is consistent with reports that the impact of Pro12Ala on obesity can be modified by fatty acid intake.…”