Adipocyte-specific deletion of PIP5K1c reduces diet-induced obesity and insulin resistance by increasing energy expenditure

Guan Huang,Puxin Chen,Cuishan Yang,Xiaohong Huang,Ying Huang,Miaoling Huang,Liping Deng,Sheng Guo,Feng Chen

doi:10.1186/s12944-021-01616-4

Abstract

BackgroundPhosphatidylinositol 4-phosphate 5-kinase type I c (PIP5K1c) catalyses the synthesis of phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2) by phosphorylating phosphatidylinositol 4 phosphate, which plays multiple roles in regulating focal adhesion formation, invasion, and cell migration signal transduction cascades. Here, a new physiological mechanism of PIP5K1c in adipocytes and systemic metabolism is reported.MethodsAdipose-specific conditional knockout mice were generated to delete the PIP5K1c gene in adipocytes. In addition, in vitro research investigated the effect of PIP5K1c deletion on adipogenesis.ResultsDeletion of PIP5K1c in adipocytes significantly alleviated high fat diet (HFD)-induced obesity, hyperlipidaemia, hepatic steatosis, and insulin resistance. PIP5K1c deficiency in adipocytes also decreased adipocyte volume in HFD-induced obese mice, whereas no significant differences were observed in body weight and adipose tissue weight under normal chow diet conditions. PIP5K1c knockout in adipocytes significantly enhanced energy expenditure, which protected mice from HFD-induced weight gain. In addition, adipogenesis was markedly impaired in mouse stromal vascular fraction (SVF) from PIP5K1c-deleted mice.ConclusionUnder HFD conditions, PIP5K1c regulates adipogenesis and adipose tissue homeostasis. Together, these data indicate that PIP5K1c could be a novel potential target for regulating fat accumulation, which could provide novel insight into the treatment of obesity.

Highlights

Obesity is a serious health concern and is associated with higher risks of developing diabetes, fatty liver and cardiovascular disease [1, 2]
Generation of adipose tissue PIP5K1c knockout mice In the present study, the authors used PIP5K1c-floxed mice crossed with adiponectin-Cre transgenic mice to KO mice fed a high fat diet (HFD) present improved metabolic profiles the authors performed Glucose tolerance test (GTT) and insulin tolerance test (ITT) to assess whether the decreased lipid storage affords beneficial effects on homeostasis in KO mice
The decreased area under the curve (AUC) of GTT and ITT (Fig. 3a-d) illustrated that compared with the with flox/flox (WT) HFD mice, a more prominent clearance of plasma glucose and ameliorated insulin sensibility were observed in KO HFD mice

Summary

Introduction

Obesity is a serious health concern and is associated with higher risks of developing diabetes, fatty liver and cardiovascular disease [1, 2]. Adipose tissue plays a crucial role in regulating homoeostasis, and the expression of inflammatory cytokines in adipose tissue correlates with BMI and insulin resistance [4,5,6,7]. WAT specializes in lipid storage and adipokine secretion to regulate energy storage and systemic insulin sensitivity [8]. Upon cold exposure and exercise, WAT can be switched into beige adipocytes in a process termed beiging [10, 11], the functions and cellular features of which are similar to those of BAT. Phosphatidylinositol 4-phosphate 5-kinase type I c (PIP5K1c) catalyses the synthesis of phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2) by phosphorylating phosphatidylinositol 4 phosphate, which plays multiple roles in regulating focal adhesion formation, invasion, and cell migration signal transduction cascades. A new physiological mechanism of PIP5K1c in adipocytes and systemic metabolism is reported

Methods

Results

Discussion

Conclusion