TY - JOUR
T1 - Inositol hexakisphosphate kinase-1 interacts with perilipin1 to modulate lipolysis
AU - Ghoshal, Sarbani
AU - Tyagi, Richa
AU - Zhu, Qingzhang
AU - Chakraborty, Anutosh
N1 - Funding Information:
We sincerely thank Prof. Solomon Snyder for sharing IP6K1-KO mice and various reagents and constructs for the research. We also thank Adele Snowman, Asif Mustafa and Krishna Juluri from Snyder lab for experimental assistance. We thank Prof. Rudolf Zechners laboratory for sharing their protocol to measure lipolysis in adipose tissue explants and Dr. James G. Granneman for providing critical comments and valuable suggestions. We thank Ana Rodrigues, Darlena Henderson and Luise Angelini for experimental assistance. We also thank Graham West, Pablo Martinez and Catherina Scharager-Tapia at the TSRI proteomic core facility and the TSRI Metabolism and Aging department for sharing reagents and instruments. The work is supported by TSRI startup fund and R01DK103746.
Publisher Copyright:
© 2016 Elsevier Ltd
PY - 2016/9/1
Y1 - 2016/9/1
N2 - 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.
AB - 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.
KW - Diabetes
KW - IP6K
KW - Lipolysis
KW - Obesity
KW - Perilipin
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U2 - 10.1016/j.biocel.2016.06.018
DO - 10.1016/j.biocel.2016.06.018
M3 - Article
C2 - 27373682
AN - SCOPUS:84978416104
VL - 78
SP - 149
EP - 155
JO - International Journal of Biochemistry
JF - International Journal of Biochemistry
SN - 1357-2725
ER -