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KMID : 0545120130230111569
Journal of Microbiology and Biotechnology
2013 Volume.23 No. 11 p.1569 ~ p.1576
t10,c12 Conjugated Linoleic Acid Upregulates Hepatic De Novo Lipogenesis and Triglyceride Synthesis via mTOR Pathway Activation
Go Gwang-Woong

Oh Sang-Nam
Park Mi-Ri
Gang Gyoung-Ok
Danielle McLean
Yang Han-Sul
Kim Young-Hoon
Abstract
In mice, supplementation of t10,c12 conjugated linoleic acid (CLA) increases liver mass and hepatic steatosis via increasing uptake of fatty acids released from adipose tissues. However, the effects of t10,c12 CLA on hepatic lipid synthesis and the associated mechanisms are largely unknown. Thus, we tested the hypothesis that gut microbiota-producing t10,c12 CLA would induce de novo lipogenesis and triglyceride (TG) synthesis in HepG2 cells, promoting lipid accumulation. It was found that treatment with t10,c12 CLA (100 ¥ìM) for 72 h increased neutral lipid accumulation via enhanced incorporation of acetate, palmitate, oleate, and 2- deoxyglucose into TG. Furthermore, treatment with t10,c12 CLA led to increased mRNA expression and protein levels of lipogenic genes including SREBP1, ACC1, FASN, ELOVL6, GPAT1, and DGAT1, presenting potential mechanisms by which CLA may increase lipid deposition. Most strikingly, t10,c12 CLA treatment for 3 h increased phosphorylation of mTOR, S6K, and S6. Taken together, gut microbiota-producing t10,c12 CLA activates hepatic de novo lipogenesis and TG synthesis through activation of the mTOR/SREBP1 pathway, with consequent lipid accumulation in HepG2 cells.
KEYWORD
conjugated linoleic acid (CLA), hepatic steatosis, de novo lipogenesis, triglyceride synthesis, nutrient sensing mTOR pathway
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