Peroxisome Proliferator-Activated Receptor ? and Its Role in Adipocyte Homeostasis and Thiazolidinedione-Mediated Insulin Sensitization.

ABSTRACT: Adipose tissue is a dynamic organ that makes critical contributions to whole-body metabolic homeostasis. Although recent studies have revealed that different fat depots have distinct molecular signatures, metabolic functions and adipogenic mechanisms, peroxisome proliferator-activated receptor ? (PPAR?) is still widely viewed as the master regulator of adipogenesis and critical for maintaining mature adipocyte function. Using an inducible, adipocyte-specific knockout system, we explored the role of PPAR? in mature adipocytes in vivo Short-term PPAR? deficiency in adipocytes reduces whole-body insulin sensitivity, but adipocytes are viable both in vitro and in vivo However, after exposure to a high-fat diet, even short-term PPAR? deficiency leads to rapid adipocyte death. When mature adipocytes are depleted of both PPAR? and CCAAT-enhancer-binding protein ? (C/EBP?), they are rapidly depleted of lipids and undergo adipocyte death, both in vitro and in vivo Surprisingly, although thiazolidinediones (TZDs; PPAR? agonists) are thought to act mainly on PPAR?, PPAR? in adipocytes is not required for the whole-body insulin-sensitizing effect of TZDs. This offers new mechanistic aspects of PPAR?/TZD action and its effect on whole-body metabolic homeostasis.

SUBMITTER: Wang QA 

PROVIDER: S-EPMC5954194 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature