Conjugated linoleic acid fails to worsen insulin resistance but induces hepatic steatosis in the presence of leptin in ob/ob mice

Abstract

Conjugated linoleic acid (CLA) induces insulin resistance preceded by rapid depletion of the adipokines leptin and adiponectin, increased inflammation, and hepatic steatosis in mice. To determine the role of leptin in CLAmediated insulin resistance and hepatic steatosis, recombinant leptin was coadministered with dietary CLA in ob/ob mice to control leptin levels and to, in effect, negate the leptin depletion effect of CLA. In a 2 3 2 factorial design, 6 week old male ob/ob mice were fed either a control diet or a diet supplemented with CLA and received daily intraperitoneal injections of either leptin or vehicle for 4 weeks. In the absence of leptin, CLA significantly depleted adiponectin and induced insulin resistance, but it did not increase hepatic triglyceride concentrations or adipose inflammation, marked by interleukin-6 and tumor necrosis factor-a mRNA expression. Insulin resistance, however, was accompanied by increased macrophage infiltration (F4/80 mRNA) in adipose tissue. In the presence of leptin, CLA depleted adiponectin but did not induce insulin resistance or macrophage infiltration. Despite this, CLA induced hepatic steatosis. In summary, CLA worsened insulin resistance without evidence of inflammation or hepatic steatosis in mice after 4 weeks. In the presence of leptin, CLA failed to worsen insulin resistance but induced hepatic steatosis in ob/ob mice.-Wendel, A. A., A. Purushotham, L-F. Liu, and M. A. Belury. Conjugated linoleic acid fails to worsen insulin resistance but induces hepatic steatosis in the presence of leptin in ob/ob mice. J. Lipid Res. 2008. 49: 98-106.

Effects of dietary conjugated linoleic acid (CLA) on spontaneously hypertensive rats

“…The discrepancy may be due in part to the fact that in this study we used rats, which have a less sensitive response to CLA with regard to body fat reduction compared to mice (Park & Pariza, 2007;Park et al, 1997;Park et al, 2005;Purushotham et al, 2007). Since it has been suggested that the enlarged liver caused by CLA contributes to the reduction of lipid deposition in extra-hepatic tissues, rats may be less prone to developing fatty liver than mice (Halade et al, 2009b;Moya-Camarena et al, 1999;Tsuboyama-Kasaoka et al, 2000;Wendel et al, 2008;Yanagita et al, 2005). However, O'Hagan and Menzel (2003) suggested increased liver weight by CLA may be a temporary response of biological systems to CLA, and potentially reversible.…”

Moderate doses of conjugated linoleic acid isomers mix contribute to lowering body fat content maintaining insulin sensitivity and a noninflammatory pattern in adipose tissue in mice☆

“…Our results are in close agreement with a recent study that, using ob/ob mice fed with 1.5% CLA, found a depletion of both leptin and adiponectin and this is accompanied by insulin resistance and macrophage infiltration. However, when mice received a daily injection of leptin, depletion of adiponectin is not so strong and there is neither insulin resistance nor macrophage infiltration, although they find hepatic steatosis [39]. Authors suggest that a basal level of both leptin and adiponectin may be critical to maintaining energy homeostasis, and our doses tested seem to fulfill this requirement.…”

Conjugated nonadecadienoic acid is more potent than conjugated linoleic acid on body fat reduction

“…They are known to be involved in controlling food intake (leptin), obesity and glucose tolerance (TNF-α), and many chronic pathologies including insulin sensitivity (adiponectin and/or leptin) [31,32]. Previously, CLA reduced expression and/or secretion of leptin and TNF-α in serum, adipose tissue and/or the liver, although effects of CLA on adiponectin were not consistent [33][34][35][36][37]. In this report, we observed that effects of CNA on these parameters were similar to CLA; reduced leptin and TNF-α but not adiponectin.…”