title: The effect of LXRα, ChREBP and Elovl6 in liver and white adipose tissue on medium- and long-chain fatty acid diet-induced insulin resistance.
abstract: OBJECTIVE
  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.affiliation: Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang 110004, China.
authors.forename: He
authors.initials: H
authors.lastname: Sun
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.forename: Shubao
authors.initials: S
authors.lastname: Wang
authors.forename: Bing
authors.initials: B
authors.lastname: He
authors.forename: Yongyan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Dongxu
authors.initials: D
authors.lastname: Piao
authors.forename: Chong
authors.initials: C
authors.lastname: Yu
authors.forename: Na
authors.initials: N
authors.lastname: Wu
authors.forename: Ping
authors.initials: P
authors.lastname: Han
mesh_terms: D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D004041:Dietary Fats / Q000009:adverse effects*; D004797:Enzyme-Linked Immunosorbent Assay; D000081031:Fatty Acid Elongases; D005227:Fatty Acids / Q000009:adverse effects*; D015309:Glucose Clamp Technique; D006946:Hyperinsulinism / Q000209:etiology / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007328:Insulin / Q000008:administration & dosage; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D000071518:Liver X Receptors; D008297:Male; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D001786:Blood Glucose; D004041:Dietary Fats; D005227:Fatty Acids; D007004:Hypoglycemic Agents; D007328:Insulin; D000071518:Liver X Receptors; C442825:Mlxipl protein, rat; C000605215:Nr1h3 protein, rat; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases
keywords: Carbohydrate response element binding protein; Hepatic glucose production; Insulin resistance; Liver X receptor α; Long-chain fatty acid elongase 6