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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyltransferases / genetics
  • Acetyltransferases / metabolism*
  • Adipose Tissue, White / drug effects
  • Adipose Tissue, White / metabolism*
  • Animals
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism*
  • Blood Glucose / metabolism
  • Blotting, Western
  • Dietary Fats / adverse effects*
  • Enzyme-Linked Immunosorbent Assay
  • Fatty Acid Elongases
  • Fatty Acids / adverse effects*
  • Glucose Clamp Technique
  • Hyperinsulinism / etiology
  • Hyperinsulinism / metabolism
  • Hypoglycemic Agents / administration & dosage
  • Insulin / administration & dosage
  • Insulin Resistance / physiology*
  • Liver / drug effects
  • Liver / metabolism*
  • Liver X Receptors
  • Male
  • Orphan Nuclear Receptors / genetics
  • Orphan Nuclear Receptors / metabolism*
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction


  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Blood Glucose
  • Dietary Fats
  • Fatty Acids
  • Hypoglycemic Agents
  • Insulin
  • Liver X Receptors
  • Mlxipl protein, rat
  • Nr1h3 protein, rat
  • Orphan Nuclear Receptors
  • RNA, Messenger
  • Acetyltransferases
  • Fatty Acid Elongases