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

Abstract

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 controlfed 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.

Anti‐obesity effects of conjugated linoleic acid, docosahexaenoic acid, and eicosapentaenoic acid

“…The adverse effects to induce fat liver and/hepatic steatosis have been also observed by other groups, and increasing studies indicate that t10, c12 isomer is the major player [9,22,97,133]. However, dietary CLA was reported to alleviate nonalcoholic fatty liver disease or hepatic steatosis in ZDF rats [134,135]. The discrepancy illustrated a relationship between the state of insulin resistance and liver-lipid metabolism, and suggested that CLA might act to favorably modify lipid metabolism in ZDF rats.…”

Dietary conjugated linoleic acid decreases adipocyte size and favorably modifies adipokine status and insulin sensitivity in obese, insulin-resistant rats

“…The protocol for the animal care procedures was approved by the University of Manitoba Protocol Management and Review Committee. Other indices for these rats related to hepatic steatosis, pancreatic function, glucose disposal, and inflammatory markers have been reported elsewhere [30,31]. The dietary formulation and the fatty acid distributions of the CLA and CTL diets have been previously reported [30].…”

Trans-10,cis-12-conjugated linoleic acid worsens renal pathology and alters cyclooxygenase derived oxylipins in obesity-associated nephropathy

“…However, rats given the t10,c12 CLA isomer had higher amounts of perirenal fat mass compared to all the other groups. We have previously observed higher relative epididymal and perirenal fat mass in younger fa/fa Zucker rats fed a CLA mixture despite no change in body weight and improvements in glycemic control, pancreatic and hepatic functions [36,66]. Greater levels of adipose mass surrounding the kidney may be related to the increased renal damage in the rats given the 10,c12 CLA diets.…”