Inhibition of metformin on high glucose-induced lipolysis in primary rat adipocytes and its mechanism
10.13699/j.cnki.1001-6821.2018.05.017
- VernacularTitle:二甲双胍抑制高浓度葡萄糖刺激的脂肪分解及机制
- Author:
Ting-Ting ZHANG
1
;
Jin-Han HE
;
Mei-Fang LIU
;
Guo-Heng XU
;
Xiao-Hui GUO
Author Information
1. 北京大学 第一医院 内分泌科
- Keywords:
metformin;
high glucose;
lipolysis;
perilipin;
adipose lipase
- From:
The Chinese Journal of Clinical Pharmacology
2018;34(5):548-551
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the inhibitory effect of metformin on high glucose-induced lipolysis and further elucidate the underlying mechanisms,for better understanding of metformin.Methods Adipocytes were isolated from epididymal fat pads of Sprague-Dawley rats.After isolation and digestion,packed adipocytes were divided into four groups according to the glucose and metformin in the media,control A group containing 5 mmol · L-1 glucose,control B group containing 25 mmol · L-1 glucose,test A group containing 500 μmol · L-1 metformin with 5 mmol · L-1 glucose and test B group containing 25 mmol · L-1 glucose with 500 μmol · L-1 metformin or at the concentrations as planned.After incubation,glycerol accumulated or released into the media in 30 minutes was determined by the use of a colorimetric assay and served as an index of lipolysis.The expressions of phosphorylated and total perilipin as well as adipose triglyceride lipase (ATGL) were examined by Western Blot.Adipose lipases activity was assayed by using an enzymatic method.Results The glycerol release in the control B and test B groups were (1.61 ± 0.08) and (0.50 ± 0.06) μmol · mL-1 packed cell volume,respectively,suggesting that metformin significantly inhibited the lipolytic action of high glucose (P ＜0.001).Such an inhibitory effect lasted from 16 h to 24 h after incubation.The adipose lipases activity in the control B and test B groups were (344.28 ± 65.98) and (200.44 ± 64.25)μmol glycerol · mg protein-1 · h-1,respectively,and thus metformin caused a 41.78％ (P ＜0.05) reduction of adipose lipases activity elevated by high glucose.Compared with control B group,metformin in test B group significantly attenuated the phosphorylation of perilipin induced by high glucose (P ＜ 0.01).However,the protein amount of total ATGL was not changed in control B group by high glucose or in test group (A and B) by metformin compared with that of control A group (all P ＞ 0.05).Conclusion Metformin inhibits high glucose-induced lipolysis through eliminating perilipin phosphorylation and suppressing lipolytic lipases activity.We suggest that such antilipolytic effect of metformin in hyperglycemia could be a molecular basis by which metformin reduces the release of free fatty acids from adipose tissue to bloodstream and thus ameliorates insulin resistance in diabetes.
