Functional interaction of hormone-sensitive lipase and perilipin in lipolysis

Abstract

This article is available online at http://www.jlr.org to the release of FFA, the process known as lipolysis. The control of lipolysis represents a complex process involving multiple regulatory events ( 1, 2 ). These broadly include lipolytic (ACTH, ␤ -adrenergic agonists, etc.) and anti-lipolytic (insulin, adenosine, etc.) hormones, their cognate receptors and signaling pathways, and lipid droplet-associated proteins, such as perilipins, cytosolic lipid binding proteins, and lipases. The complexity of the regulation of lipolysis has further increased in recent years with the identifi cation of a large number of proteins that are found associated with the lipid droplets stored within adipocytes and with the realization of the dynamic nature of the proteins that populate lipid droplets.The major lipid droplet-associated protein in differentiated adipocytes is perilipin (Plin) A, which is also the most highly phosphorylated protein in adipose cells following cyclic AMP-dependent protein kinase (PKA) activation ( 3 ). Plin A plays an essential role in regulating lipolysis, as evidenced by the 3-fold elevation in basal lipolysis and the absence of PKA-stimulated lipolysis in adipocytes from Plin A null mice ( 4, 5 ). Moreover, using model cell systems, it has been shown that Plin A promotes PKA-stimulated lipolysis ( 6-8 ). Thus, it appears that Plin A has dual functions of acting as a barrier to suppress basal or constitutive lipolysis and of enhancing PKA-stimulated lipolysis.Intracellular lipases are instrumental in lipolysis, and there are many proteins that are predicted to have lipase or esterase activity that are expressed in adipose tissue. It had long been considered that hormone-sensitive lipase (HSL) ( 9, 10 ) was the rate-limiting enzyme for lipolysis; however, examination of the nonobese HSL null mouse indicated the existence and importance of other lipases The major contribution of adipose tissue to whole-body metabolism is the storage of energy in the form of triacylglycerols and the mobilization of this stored energy leading

Fat-specific protein 27 modulates nuclear factor of activated T cells 5 and the cellular response to stress

“…NFAT5 coimmunoprecipitated with FSP27 ( Fig. 4B ), but another cytosolic protein, Flag-HSL, expressed as a control, did not coimmunoprecipitate with FSP27; however, Flag-HSL was coimmunoprecipitated when HA-Plin1 was coexpressed, consistent with our previous observations ( 22 ). To document the inter action of endogenously expressed FSP27 and NFAT5, proteins extracted from the fat cake obtained from isolated normal mouse adipose cells were immunoprecipitated with anti-NFAT5 antibody and then immunoblotted with anti-FSP27 antibody ( Fig.…”

Effects of lipoic acid on lipolysis in 3T3-L1 adipocytes

“…Moreover, the lipid droplet protein perilipin is also phosphorylated by PKA. Upon phosphorylation, perilipin shifts to the cytoplasm, accessibility of HSL to the lipid surface is promoted, and lipolysis is enhanced (45)(46)(47). The results of our study suggest a key role of PKA-induced lipolysis in the , the AMPK activator AICAR, the ERK1/2 inhibitor PD98059 (PD), and the PKA inhibitor H89.…”

Triacylglycerol lipases and metabolic control: implications for health and disease

“…Readers are directed to an excellent recent review of this topic (7). PKA phosphorylation of perilipin A is critical for HSL lipolytic action at the LD (53), which is mediated by direct binding, although the exact residues have not been determined (28,66). This regulation is not relevant for other key tissues of FA metabolism that do not express perilipin A.…”