Conjugated linoleic acid reduces hepatic steatosis, improves liver function, and favorably modifies lipid metabolism in obese insulin-resistant rats

CLA has been shown to induce or suppress excess liver lipid accumulation in various animal models. Interestingly, the state of insulin resistance may be an important modulator of this effect. The objective of the current study was to determine how feeding a dietary CLA mixture would affect liver lipid accumulation in insulin-resistant/obese and lean rats in relation to liver function, lipidemia, liver TAG and phospholipid FA composition, and expression of hepatic markers of FA transport, oxidation, and synthesis. Six-week-old fa/fa and lean Zucker rats (n=20/genotype) were fed either a 1.5% CLA mixture or a control diet for 8 wk. CLA supplementation reduced liver lipid concentration of fa/fa rats by 62% in concurrence with improved liver function (lower serum alanine aminotransferase and alkaline phosphatase) and favorable modification of the serum lipoprotein profile (reduced VLDL and LDL and elevated HDL) compared with control-fed fa/fa rats. The fa/fa genotype had two-thirds the amount of CLA (as % total FA) incorporated into liver TAG and phospholipids compared with the lean genotype. In both genotypes, CLA altered the hepatic FA profile (TAG greater than phospholipids) and these changes were explained by a desaturase enzyme index. Liver-FA-binding protein and acyl CoA oxidase, markers of FA transport and oxidation, respectively, were expressed at higher levels in CLA-fed fa/fa rats. In summary, these results illustrate a strong relationship between the state of insulin resistance and liver lipid metabolism and suggest that CLA acts to favorably modify lipid metabolism in fa/fa Zucker rats.