Isomer-Specific Antidiabetic Properties of Conjugated Linoleic Acid

Abstract

Conjugated linoleic acid (CLA) isomers have a number of beneficial health effects, as shown in biomedical studies with animal models. Previously, we reported that a mixture of CLA isomers improved glucose tolerance in ZDF rats and activated peroxisome proliferatoractivated receptor (PPAR)-␥ response elements in vitro. Here, our aim was to elucidate the effect(s) of specific CLA isomers on whole-body glucose tolerance, insulin action in skeletal muscle, and expression of genes important in glucose and lipid metabolism. ZDF rats were fed either a control diet (CON), one of two CLA supplemented diets (1.5% CLA) containing differing isoforms of CLA (47% c9,t11; 47.9% c10,t12, 50:50; or 91% c9,t11, c9,t11 isomers), or were pair-fed CON diet to match the intake of 50:50. The 50:50 diet reduced adiposity and improved glucose tolerance compared with all other ZDF treatments. Insulin-stimulated glucose transport and glycogen synthase activity in skeletal muscle were improved with 50:50 compared with all other treatments. Neither phosphatidlyinositol 3-kinase activity nor Akt activity in muscle was affected by treatment. Uncoupling protein 2 in muscle and adipose tissue was upregulated by c9,t11 and 50:50 compared with ZDF controls. PPAR-␥ mRNA was downregulated in liver of c9,t11 and pair-fed ZDF rats. Thus, the improved glucose tolerance in 50:50 rats is attributable to, at least in part, improved insulin action in muscle, and CLA effects cannot be explained simply by reduced food intake.

Interactions of conjugated linoleic acid and lipoic acid on insulin action in the obese Zucker rat

“…8,9 In the present investigation, some improvements in the deranged metabolic regulation of the female obese Zucker rat were elicited at a substantially lower dose of CLA (0.3 mg/kg). For example, the low-dose CLA treatment caused decreases in fasting plasma glucose and FFAs (Table 1), improved whole-body glucose tolerance and insulin sensitivity (Fig 2), and increased insulin-mediated glucose transport activity in fast-glycolytic muscle (Fig 3).…”

“…However, recent studies by Riserus et al 39,40 in abdominally obese human males have indicated that treatment with CLA (specifically the trans-10, cis-12 isomer) actually worsened slightly insulin resistance (19%) and glycemia (4%) and was associated with an increase in oxidative stress (based on plasma isoprostanes). Based on these limited clinical findings, and in the context of the positive results from the present study and previous investigations, 8,9 it is clear that subjects in human clinical trials of CLA must be selected very carefully to ensure that they will be appropriate candidates for CLA treatment of obesity and insulin resistance.…”

“…8,9 These CLA-induced improvements in glucose metabolism were possibly related to a decrease in muscle oxidative stress (Figs 4 and 6). However, recent studies by Riserus et al 39,40 in abdominally obese human males have indicated that treatment with CLA (specifically the trans-10, cis-12 isomer) actually worsened slightly insulin resistance (19%) and glycemia (4%) and was associated with an increase in oxidative stress (based on plasma isoprostanes).…”

“…CLA is a naturally occurring compound found in the meat and milk of ruminating animals. In addition to its actions against cancer, 6 CLA has been shown to also have anti-obesity 7 and antidiabetic 8,9 effects and to mediate a repartitioning of the fat-to-lean mass ratio. [10][11][12] CLA is thought to act through the peroxisome proliferator-activated receptor-␥ (PPAR-␥) to elicit the beneficial effects in animal models of diabetes.…”

Os efeitos do ácido linoléico conjugado no metabolismo animal: avanço das pesquisas e perspectivas para o futuro

“…O aumento da termogênese induzida pelo CLA tem sido discutido também como responsável pela redução da gordura corporal, já demonstrada em camundongos AKR/J, Std ddY e C57BL/6J e ratos ZDF 88,[121][122][123] . Segundo Tsuboyama-Kasaoka et al 88 e Ryder et al 122 , o aumento do gasto energé-tico observado nesses animais é resultante do aumento da expressão de genes que codificam as proteínas desacopladoras (UCP), especialmente a UCP-2, visto que os autores encontraram aumento dos níveis tanto do mRNA quanto da proteína no tecido adiposo branco, músculo esquelético e fígado dos animais.…”