Peroxisome Proliferator-Activated Receptor γ2 Controls the Rate of Adipose Tissue Lipid Storage and Determines Metabolic Flexibility

Abstract

SummaryOne understudied function of white adipose tissue (AT) is its role in postprandial lipid buffering. In this study, we demonstrate that mice lacking the adipose tissue-specific transcription factor peroxisome proliferator-activated receptor γ2 (PPARγ2) exhibit a defect in their rate of adipose tissue lipid storage. Impaired adipose tissue storage rate reduces metabolic flexibility, without compromising fasted glucose tolerance or insulin sensitivity, even following prolonged high-fat feeding. However, acutely overfeeding PPARγ2-KO mice caused a 10-fold increase in insulin levels compared with controls. Although impaired adipose tissue storage rate did not result in insulin resistance in young mice, 1-year-old PPARγ2-KO mice developed skeletal muscle insulin resistance. Our data indicate that failed adipose tissue storage may occur prior to defects in glucose handling and that overfeeding protocols may uncover genes controlling adipose tissue storage rate, as opposed to capacity, and act as a diagnostic test for early-stage human metabolic disease.

The glycoprotein follistatin-like 1 promotes brown adipose thermogenesis

“…PPARγ, particular the PPARγ2 isoform, is a key regulatory factor for brown adipocyte differentiation and BAT function [7,45]. In addition, Sirt1-dependent deacetylation of PPARγ and CDK inhibitor-induced dephosphorylation at S273 of PPARγ are important in browning of WAT [46].…”

A high-throughput platform for detailed lipidomic analysis of a range of mouse and human tissues

“…Liquid chromatography-mass spectrometry LC-MS was run as we described in our recent studies [14,16,26,27], with the additional use of CID for analyses described here. For all runs, chromatographic separation of lipid and triglycerides was achieved using a Waters Acquity UPLC CSH C18 (50 mm × 2•1 mm, 1•7 mm) LC-column with a Shimadzu UPLC system (Shimadzu UK Limited, Milton Keynes, UK).…”

“…Liquid chromatography-mass spectrometry (LC-MS) was used to verify the signals identified in DI-MS [14,26,27,39] and exploit in-source fragmentation (CID) in order to identify the fatty acids associated with individual lipid variables. Verification of the existence of signals observed in DI-MS using LC-MS is scientifically valuable as it provides further evidence of the molecular structure of the species identified.…”

Altered triglyceride and phospholipid metabolism predates the diagnosis of gestational diabetes in obese pregnancy

“…LCMS was run in a similar manner to recent studies 29,42,43 -Chromatographic separation of lipid and triglycerides was achieved using a Waters Acquity UPLC CSH C18 (50 mm × 2.1 mm, 1.7 mm) LC-column with a Shimadzu UPLC system (Shimadzu UK Limited, Wolverton, Milton Keynes). The column was maintained at 55 °C with a flow rate of 0.5 mL min −1 .…”