First Author | Rodriguez-Cuenca S | Year | 2012 |
Journal | Mol Cell Biol | Volume | 32 |
Issue | 8 | Pages | 1555-65 |
PubMed ID | 22310664 | Mgi Jnum | J:183680 |
Mgi Id | MGI:5319097 | Doi | 10.1128/MCB.06154-11 |
Citation | Rodriguez-Cuenca S, et al. (2012) Peroxisome proliferator-activated receptor gamma-dependent regulation of lipolytic nodes and metabolic flexibility. Mol Cell Biol 32(8):1555-65 |
abstractText | Optimal lipid storage and mobilization are essential for efficient adipose tissue. Nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) regulates adipocyte differentiation and lipid deposition, but its role in lipolysis and dysregulation in obesity is not well defined. This investigation aimed to understand the molecular impact of dysfunctional PPARgamma on the lipolytic axis and to explore whether these defects are also confirmed in common forms of human obesity. For this purpose, we used the P465L PPARgamma mouse as a model of dysfunctional PPARgamma that recapitulates the human ppargamma mutation (P467L). We demonstrated that defective PPARgamma impairs catecholamine-induced lipolysis. This abnormal lipolytic response is exacerbated by a state of positive energy balance in leptin-deficient ob/ob mice. We identified the protein kinase A (PKA) network as a PPARgamma-dependent regulatory node of the lipolytic response. Specifically, defective PPARgamma is associated with decreased basal expression of prkaca (PKAcatalpha) and d-akap1, the lipase genes Pnplaz (ATGL) and Lipe (HSL), and lipid droplet protein genes fsp27 and adrp in vivo and in vitro. Our data indicate that PPARgamma is required for activation of the lipolytic regulatory network, dysregulation of which is an important feature of obesity-induced insulin resistance in humans. |