Isomer-specific actions of conjugated linoleic acid on muscle glucose transport in the obese Zucker rat

Abstract

The fatty acid-conjugated linoleic acid (CLA) enhances glucose tolerance and insulin action on skeletal muscle glucose transport in rodent models of insulin resistance. However, no study has directly compared the metabolic effects of the two primary CLA isomers, cis-9, trans-11-CLA (c9,t11-CLA) and trans-10, cis-12-CLA (t10,c12-CLA). Therefore, we assessed the effects of a 50:50 mixture of these two CLA isomers (M-CLA) and of preparations enriched in either c9,t11-CLA (76% enriched) or t10,c12-CLA (90% enriched) on glucose tolerance and insulin-stimulated glucose transport in skeletal muscle of the insulin-resistant obese Zucker ( fa/ fa) rat. Animals were treated daily by gavage with either vehicle (corn oil), M-CLA, c9,t11-CLA, or t10,c12-CLA (all CLA treatments at 1.5 g total CLA/kg body wt) for 21 consecutive days. During an oral glucose tolerance test, glucose responses were reduced ( P < 0.05) by 10 and 16%, respectively, in the M-CLA and t10,c12-CLA animals, respectively, whereas insulin responses were diminished by 21 and 19% in these same groups. There were no significant alterations in these responses in the c9,t11-CLA group. Insulin-mediated glucose transport activity was enhanced by M-CLA treatment in both type I soleus (32%) and type IIb epitrochlearis (58%) muscles and by 36 and 48%, respectively, with t10,c12-CLA. In the soleus, these increases were associated with decreases in protein carbonyls (index of oxidative stress, r = -0.616, P = 0.0038) and intramuscular triglycerides ( r = -0.631, P = 0.0028). Treatment with c9,t11-CLA was without effect on these variables. These results suggest that the ability of CLA treatment to improve glucose tolerance and insulin-stimulated glucose transport activity in insulin-resistant skeletal muscle of the obese Zucker rat are associated with a reduction in oxidative stress and muscle lipid levels and can be specifically ascribed to the actions of the t10,c12 isomer. In the obese Zucker rat, the c9,t11 isomer of CLA is metabolically neutral.

10E,12Z-conjugated linoleic acid impairs adipocyte triglyceride storage by enhancing fatty acid oxidation, lipolysis, and mitochondrial reactive oxygen species

“…However, despite its ability to reduce adiposity, 10E,12Z-CLA has also been shown to promote adipose tissue infl ammation ( 13,14 ), insulin resistance (15)(16)(17), hepatic steatosis ( 18,19 ), and an atherogenic lipid profi le ( 20,21 ) in rodent and human studies. With simultaneous benefi cial and detrimental side effects, more research is needed to determine whether this fatty acid is safe and appropriate as a dietary supplement marketed for weight loss.…”

Addition of conjugated linoleic acid in whole milk improves lipid profile in high fat diet induced hypercholesterolemia of rats

“…It was reported that CLA isomer trans-10, cis-12, has been linked with negative effect on health such as impairment in glucose tolerance and reduced insulin sensitivity as well. 26,27 The isomer trans-10, cis-12 CLA has been associated with lower weight reducing effect compared with the cis-9, trans-11 CLA due to the ability of the trans-10, cis-12 CLA in modulating several genes involved in lipolysis and fatty acid oxidation. 5,27,28 Furthermore, the dose of CLA used in this study is not met the physiological dose to promote human benefit.…”

Effects of dietary conjugated linoleic acids in the control of adiposity and obesity‐related disorders

“…In contrast, in a model of genetically obese diabetic rats (ZDF), CLA treatment restored glucose tolerance and insulin responsiveness in muscles [50][51][52]. In this model, trans-10, cis-12 CLA exerted an isomer-specific anti-diabetic effect, which was associated with a reduction of lipid stores in muscles that secondarily improved glucose utilization [52]. Consequently, trans-10, cis-12 CLA could exert opposite effects on glucose homeostasis according to the species or the metabolic state of the animal models.…”

“…However, several studies in mice have shown that trans-10, cis-12 CLA intake induced hyperinsulinemia and/or insulin resistance with-out any changes in glycemia [20,43,45,49]. In contrast, in a model of genetically obese diabetic rats (ZDF), CLA treatment restored glucose tolerance and insulin responsiveness in muscles [50][51][52]. In this model, trans-10, cis-12 CLA exerted an isomer-specific anti-diabetic effect, which was associated with a reduction of lipid stores in muscles that secondarily improved glucose utilization [52].…”