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.
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.
Authors: Friedhelm Schroeder; Avery L McIntosh; Gregory G Martin; Huan Huang; Danilo Landrock; Sarah Chung; Kerstin K Landrock; Lawrence J Dangott; Shengrong Li; Martin Kaczocha; Eric J Murphy; Barbara P Atshaves; Ann B Kier Journal: Lipids Date: 2016-04-27 Impact factor: 1.880
Authors: Kathrin Weiss-Hersh; Ada L Garcia; Tamás Marosvölgyi; Mónika Szklenár; Tamás Decsi; Ralph Rühl Journal: Eur J Nutr Date: 2019-11-01 Impact factor: 5.614
Authors: Andrea G Braundmeier-Fleming; Cassandra S Skenandore; Lesly Gil; Victoria Jacobsen; Melissa Cregger; Taylor Badger; Mallory Karr; Guoyao Wu; Stephen B Smith; Annie E Newell-Fugate Journal: J Anim Sci Biotechnol Date: 2020-03-16