Upregulation of GPR50 in a white adipose depot of diet‐induced obese mice requires intact leptin signaling (711.11)

Abstract

Whole transcriptome analysis of white adipose from C57BL6 mice fed control (10% kcal) or high‐fat diet (HFD; 60% kcal) for 12 and 24 wks identified GPR50 as the most upregulated gene in response to a HFD (eg, 60‐fold in reproductive adipose at 12 wks). We tested the hypothesis that GPR50 upregulation occurs earlier than 12 wks of HFD in reproductive adipose of C57BL6 mice and in genetic models of obesity. GPR50 expression was assessed via qRT‐PCR in reproductive adipose from C57BL6 mice fed control or HFD for 1, 4, 12 and 24 wks and in db/db leptin receptor‐deficient and melanocortin 4 receptor‐deficient (MC4R‐/‐) mice. GPR50 adipose expression of 1 wk HFD mice trended higher than control (0.44‐fold±0.69, n=4; P=0.28). However, 4 wks HFD was associated with significantly higher GPR50 expression compared to control (2.77‐fold±0.73, n=4; P=0.01). qRT‐PCR confirmed GPR50 increase in adipose with 12 and 24 wks HFD compared to controls (26.4‐fold±0.73, n=4; P<0.0001 & 221‐fold±2.8, n=4; P<0.0001, respectively). Adipose GPR50 expression was less in 12 wks HFD db/db mice than in HFD C57BL6 when both were compared to their control (0.61‐fold±0.13, n=2‐3). GPR50 in adipose of MC4R‐/‐ increased compared to control but not to the same degree as 24 wks HFD C57BL6 (4.9‐fold±2.1, n=4; P=0.03). These data indicate that intact leptin signaling may be required for GPR50 upregulation in white adipose of HFD‐induced obese mice.Grant Funding Source: Supported by NIH HL‐089884 and HL‐107632