title: Inositol hexakisphosphate kinase-1 interacts with perilipin1 to modulate lipolysis.
abstract: Lipolysis leads to the breakdown of stored triglycerides (TAG) to release free fatty acids (FFA) and glycerol which is utilized by energy expenditure pathways to generate energy. Therefore, a decrease in lipolysis augments fat accumulation in adipocytes which promotes weight gain. Conversely, if lipolysis is not complemented by energy expenditure, it leads to FFA induced insulin resistance and type-2 diabetes. Thus, lipolysis is under stringent physiological regulation, although the precise mechanism of the regulation is not known. Deletion of inositol hexakisphosphate kinase-1 (IP6K1), the major inositol pyrophosphate biosynthetic enzyme, protects mice from high fat diet (HFD) induced obesity and insulin resistance. IP6K1-KO mice are lean due to enhanced energy expenditure. Therefore, IP6K1 is a target in obesity and type-2 diabetes. However, the mechanism/s by which IP6K1 regulates adipose tissue lipid metabolism is yet to be understood. Here, we demonstrate that IP6K1-KO mice display enhanced basal lipolysis. IP6K1 modulates lipolysis via its interaction with the lipolytic regulator protein perilipin1 (PLIN1). Furthermore, phosphorylation of IP6K1 at a PKC/PKA motif modulates its interaction with PLIN1 and lipolysis. Thus, IP6K1 is a novel regulator of PLIN1 mediated lipolysis.
authors.affiliation: Department of Metabolism and Aging, The Scripps Research Institute, Jupiter, FL 33458, USA.
authors.forename: Sarbani
authors.initials: S
authors.lastname: Ghoshal
authors.affiliation: The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Richa
authors.initials: R
authors.lastname: Tyagi
authors.affiliation: Department of Metabolism and Aging, The Scripps Research Institute, Jupiter, FL 33458, USA.
authors.forename: Qingzhang
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Department of Metabolism and Aging, The Scripps Research Institute, Jupiter, FL 33458, USA. Electronic address: achakrab@scripps.edu.
authors.forename: Anutosh
authors.initials: A
authors.lastname: Chakraborty
mesh_terms: D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D055786:Gene Knockout Techniques; D008066:Lipolysis; D008297:Male; D051379:Mice; D000070778:Perilipin-1 / Q000378:metabolism*; D010766:Phosphorylation; D017856:Phosphotransferases (Phosphate Group Acceptor) / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism
chemical_list: C485444:Ihpk1 protein, mouse; D000070778:Perilipin-1; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D017856:Phosphotransferases (Phosphate Group Acceptor)
keywords: Diabetes; IP6K; Lipolysis; Obesity; Perilipin