LA and ALA prevent glucose intolerance in obese male rats without reducing reactive lipid content, but cause tissue-specific changes in fatty acid composition

Am J Physiol Regul Integr Comp Physiol. 2016 Apr 1;310(7):R619-30. doi: 10.1152/ajpregu.00297.2015. Epub 2016 Jan 13.


While the cause of Type 2 diabetes remains poorly defined, the accumulation of reactive lipids within white adipose tissue, skeletal muscle, and liver have been repeatedly implicated as underlying mechanisms. The ability of polyunsaturated fatty acids (PUFAs) to prevent the development of insulin resistance has gained considerable interest in recent years; however, the mechanisms-of-action remain poorly described. Therefore, we determined the efficacy of diets supplemented with either linoleic acid (LA) or α-linolenic acid (ALA) in preventing insulin resistance and reactive lipid accumulation in key metabolic tissues of the obese Zucker rat. Obese Zucker rats displayed impaired glucose homeostasis and reduced n-3 and n-6 PUFA content in the liver and epididymal white adipose tissue (EWAT). After the 12-wk feeding intervention, both LA- and ALA-supplemented diets prevented whole body glucose and insulin intolerance; however, ALA had a more pronounced effect. These changes occurred in association with n-3 and n-6 accumulation in all tissues studied, albeit to different extents (EWAT > liver > muscle). Triacylglycerol (TAG), diacylglycerol (DAG), ceramide, and sphingolipid accumulation were not attenuated in obese animals supplemented with either LA or ALA, suggesting that preservation of glucose homeostasis occurred independent of changes in reactive lipid content. However, PUFA-supplemented diets differentially altered the fatty acid composition of TAGs, DAGs, and PLs in a tissue-specific manner, suggesting essential fatty acid metabolism differs between tissues. Together, our results indicate that remodeling of the fatty acid composition of various lipid fractions may contribute to the improved glucose tolerance observed in obese rats fed PUFA-supplemented diets.

Keywords: DAG; TAG; WAT; ceramides; insulin resistance; liver; muscle; polyunsaturated fatty acids; reactive lipids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism
  • Administration, Oral
  • Animals
  • Dietary Fats, Unsaturated / metabolism
  • Dietary Supplements
  • Fatty Acids / metabolism*
  • Glucose / metabolism*
  • Glucose Tolerance Test
  • Insulin Resistance*
  • Linoleic Acid / administration & dosage
  • Linoleic Acid / metabolism*
  • Lipid Metabolism*
  • Liver / metabolism
  • Male
  • Muscle, Skeletal / metabolism
  • Rats
  • Rats, Zucker
  • alpha-Linolenic Acid / administration & dosage
  • alpha-Linolenic Acid / metabolism*


  • Dietary Fats, Unsaturated
  • Fatty Acids
  • alpha-Linolenic Acid
  • Linoleic Acid
  • Glucose