Molecular Mechanism of Action for the Geranyl Flavonoid to Counter Dyslipidemia in Diabetic Milieu

Hai Niu^{1, 2,} , Ke Li^{1, 3}, Limei Ma¹, Weihong Gong^{1, 4} and Wen Huang^{1, 3,}

¹Laboratory of Ethnopharmacology, Institute for Nanobiomedical Technology and Membrane Biology, Regenerative Medicine Research Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, China

²College of Mathematics, Sichuan University, Chengdu 610064, P.R. China

³College of Light Industry, Textile and Food Engineering, Sichuan University, Chengdu, Sichuan 610065, PR China

⁴School of Basic Clinical Medical, Beijing University of Traditional Chinese Medicine, Beijing 100029, China

Cite this paper:
Hai Niu, Ke Li, Limei Ma, Weihong Gong and Wen Huang. Molecular Mechanism of Action for the Geranyl Flavonoid to Counter Dyslipidemia in Diabetic Milieu. Journal of Food and Nutrition Research. 2015; 3(6):371-378. doi: 10.12691/jfnr-3-6-3

Abstract

This work was to examine the effect of 3’-methyl-4’, 7-dihydroxyflavanone, a geranyl flavonoid (GF), on hepatocellular AMPK activity and lipid levels in HepG2 cells and diabetic mice, and identify molecular mechanism of the GF action on remedying dyslipidemia. The AMPK activation and lipid-lowering effect of the GF in diabetic mice and in HepG2 cells paralleled observations. The GF activated AMPK in HepG2 cells treated with high glucose, and enhance phosphorylation of ACC1 and ACC2, two isoforms of ACC, resulting in decrease in ACC activity and hepatic lipids. As demonstrated in cells overexpressing a dominant-negative AMPK mutant, the effect of GF was shown to be mediated by the activation of AMPK. The AMPK was activated relatively rapidly by GF and well before any potential change in adenosine triphosphate (ATP) level was detected. Thus, both in vivo and in vitro inhibition of AMPK, activation of ACC, and hepatocellular lipid accumulation caused by sustained high glucose levels was effectively counteracted by activating AMPK with treatment of GF. It can be conclude that GF lower lipids both in vivo and in vitro by activating AMPK and inactivating ACC, and consequently down-regulating fatty acid synthesis. The work provides a strong evidence for GF as a new therapeutic agent to definitively remedy dyslipidemia in diabetic milieu.

Keywords:
geranyl flavonoid AMPK ACC diabetic milieu HepG2 cells dyslipidemia

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