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Mol Nutr Food Res. 2015 Nov;59(11):2303-14. doi: 10.1002/mnfr.201500107. Epub 2015 Aug 12.

Obesity-induced miR-15b is linked causally to the development of insulin resistance through the repression of the insulin receptor in hepatocytes.

Author information

1
Department of Biochemistry, Dongguk University College of Medicine, Gyeongju, Korea.
2
Endocrine Channelopathy, Channelopathy Research Center, Dongguk University College of Medicine, Goyang, Korea.

Abstract

SCOPE:

Obesity increases intracellular lipid accumulation in key tissues or organs, which often leads to metabolic dysfunction and insulin resistance. Diets rich in saturated fatty acid (SFA) exacerbate obesity and hepatic steatosis, which accentuate the risk of insulin resistance and type 2 diabetes (T2DM). Although microRNAs (miRNAs) play a critical role in the regulation of gene expression, the implication of obesity-induced miRNAs in metabolic disorders particularly in the development of insulin resistance is largely unknown. Here, we investigated the implication of miR-15b, which is induced by SFA palmitate or obesity, in hepatic insulin resistance.

METHODS AND RESULTS:

Diet-induced obesity (DIO) in mice developed hyperglycemia and insulin resistance, accompanying with a reduction of insulin receptor (INSR) expression. Palmitate impaired insulin signaling as well as a decrease of INSR in hepatocytes. The expression of miR-15b was upregulated by DIO or palmitate in hepatocytes. Furthermore, the overexpression of miR-15b suppressed the protein expression of INSR through targeting INSR 3' untranslated region directly, resulting in an impairment of the insulin signaling and glycogen synthesis in hepatocytes.

CONCLUSION:

These results unveil a novel mechanism whereby miR-15b is linked causally to the pathogenesis of hepatic insulin resistance in SFA-induced obesity.

KEYWORDS:

INSR; IRS-1; Insulin resistance; MiR-15b; MicroRNA; Palmitate; Saturated fatty acid

PMID:
26179126
DOI:
10.1002/mnfr.201500107
[Indexed for MEDLINE]

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