| First Author | Montgomery MK | Year | 2019 |
| Journal | FASEB J | Volume | 33 |
| Issue | 12 | Pages | 13267-13279 |
| PubMed ID | 31533003 | Mgi Jnum | J:297689 |
| Mgi Id | MGI:6472506 | Doi | 10.1096/fj.201900909RR |
| Citation | Montgomery MK, et al. (2019) The role of Ap2a2 in PPARalpha-mediated regulation of lipolysis in adipose tissue. FASEB J 33(12):13267-13279 |
| abstractText | Adipose tissue plays a major role in the regulation of systemic metabolic homeostasis, with the AP2 adaptor complex being important in clathrin-mediated endocytosis (CME) of various cell surface receptors, including glucose transporter 4, the insulin receptor, and beta-adrenergic receptors (ARs). One of the AP2 subunits, adaptor-related protein complex 2, alpha2 subunit (Ap2a2), has recently been identified as a peroxisome proliferator-activated receptor (PPAR)alpha target gene. The effects of PPARalpha on the AP2 adaptor complex and CME are unknown. We generated adipocyte-specific Ap2a2 knockout mice and investigated their metabolism when fed a standard chow or high-fat diet, without and with supplementation with the PPARalpha-agonist WY-14643 (WY). Although Ap2a2 deletion had only minor effects on glycaemic control, it led to substantial impairment in beta-adrenergic activation of lipolysis, as evidenced by a loss of cAMP response, PKA activation, and glycerol/fatty acid release. These differences were related to increased cell surface localization of the beta2- and beta3-ARs. Lipolytic defects were accompanied by impaired WY-mediated loss of fat mass and whole-body fat oxidation. This study demonstrates a novel role for PPARalpha in beta-adrenergic regulation of adipose tissue lipolysis and for adipose tissue in supplying adequate substrate to other peripheral tissues to accommodate the increase in systemic fatty acid oxidation that occurs upon treatment with PPARalpha agonists.-Montgomery, M. K., Bayliss, J., Keenan, S., Rhost, S., Ting, S. B., Watt, M. J. The role of Ap2a2 in PPARalpha-mediated regulation of lipolysis in adipose tissue. |
