Inositol hexakisphosphate kinase-1 interacts with perilipin1 to modulate lipolysis

Sarbani Ghoshal, Richa Tyagi, Qingzhang Zhu, Anutosh Chakraborty

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)149-155
Number of pages7
JournalInternational Journal of Biochemistry and Cell Biology
Volume78
DOIs
StatePublished - Sep 1 2016
Externally publishedYes

Keywords

  • Diabetes
  • IP6K
  • Lipolysis
  • Obesity
  • Perilipin

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Fingerprint

Dive into the research topics of 'Inositol hexakisphosphate kinase-1 interacts with perilipin1 to modulate lipolysis'. Together they form a unique fingerprint.

Cite this