Inactivation of MAPK in Epididymal Fat and Amelioration of Triglyceride Secretion by Injection of GRK2 SiRNA in Ob/ob Mice

Overview

Journal Naunyn Schmiedebergs Arch Pharmacol

Specialty Pharmacology

Date 2018 Jun 28

PMID 29946903

Authors

Kumiko Taguchi

Nanami Bessho

Mari Hida

Haruka Narimatsu

Takayuki Matsumoto

Tsuneo Kobayashi

Affiliations

Soon will be listed here.

Abstract

Abnormal G protein-coupled receptor kinase 2 (GRK2) accumulation has a crucial role in the development of insulin resistance and diabetes. Although GRK2 siRNA transfection in the liver improves insulin resistance-related vascular complications, the effects of GRK2 siRNA in lipid metabolism and obesity remain unknown. To investigate how GRK2 siRNA affects obesity, ob/ob mice were transfected with GRK2 siRNA, mainly in the liver, by using a hydrodynamic-based procedure. Epididymal fat, glucose, triglyceride, non-esterified fatty acid (NEFA), and alanine transaminase activity were higher in the control siRNA-transfected ob/ob mice than in the control siRNA-transfected Lean mice, but these parameters were reduced by GRK2 siRNA transfection into the ob/ob mice. GRK2 expression in epididymal fat was not altered among the 3 groups, although hepatic GRK2 expression was higher in the control siRNA-transfected ob/ob mice than in the control siRNA-transfected Lean mice. Additionally, we found that Akt interacted with GRK2 in the liver. Furthermore, phosphorylation levels of ERK1/2 and JNK were higher in the epididymal fats from the control siRNA-transfected ob/ob mice than in those from the control siRNA-transfected Lean mice, but they were lowered by transfection with GRK2 siRNA. The study results showed that GRK2 siRNA improved blood triglyceride levels and abnormal or excessive activity of mitogen-activated protein kinases in epididymal fat. This effect may be promoted by inhibition of the NEFA production pathway in the liver. Therefore, the interaction of organs (hepatic GRK2-epididymal fat) may help improve insulin resistance and diabetes-associated pathophysiology.

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