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Diabetes Res Clin Pract. 2013 Dec;102(3):183-92. doi: 10.1016/j.diabres.2013.10.010. Epub 2013 Oct 26.

The effect of LXRα, ChREBP and Elovl6 in liver and white adipose tissue on medium- and long-chain fatty acid diet-induced insulin resistance.

Author information

1
Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang 110004, China.

Abstract

AIMS:

We aimed to investigate the effects of LXRα, ChREBP and Elovl6 in the development of insulin resistance-induced by medium- and long-chain fatty acids.

METHODS:

Sprague Dawley rats were fed a standard chow diet (Control group) or a high-fat, high sucrose diet with different fat sources (coconut oil, lard, sunflower and fish oil) for 8 weeks. These oils were rich in medium-chain saturated fatty acids (MCFA group), long-chain saturated fatty acids (LCFA group), n-6 and n-3 long-chain polyunsaturated fatty acids (n-6 PUFA and n-3 PUFA groups), respectively, which had different chain lengths and degrees of unsaturation. Hyperinsulinemic-euglycemic clamp with [6-(3)H] glucose infusion was performed in conscious rats to assess hepatic insulin sensitivity.

RESULTS:

LCFA and n-6 PUFA groups induced hepatic insulin resistance and increased liver X receptor α (LXRα), carbohydrate response element binding protein (ChREBP) and long-chain fatty acid elongase 6 (Elovl6) expression in liver and white adipose tissue (WAT). Furthermore, LCFA and n-6 PUFA groups suppressed Akt serine 473 phosphorylation in liver and WAT. By contrast, in liver and WAT, MCFA and n-3 PUFA groups decreased LXRα, ChREBP and Elovl6 expression and improved insulin signaling and insulin resistance, but Akt serine 473 phosphorylation was not restored by MCFA group in WAT.

CONCLUSIONS:

This study demonstrated that the mechanism of the different effects of medium- and long-chain fatty acids on hepatic insulin resistance involves LXRα, ChREBP and Elovl6 alternations in liver and WAT. It points to a new strategy for ameliorating insulin resistance and diabetes through intervention on Elovl6 or its control genes.

KEYWORDS:

Carbohydrate response element binding protein; Hepatic glucose production; Insulin resistance; Liver X receptor α; Long-chain fatty acid elongase 6

PMID:
24262945
DOI:
10.1016/j.diabres.2013.10.010
[Indexed for MEDLINE]

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