Effects of specific conjugated linoleic acid isomers on growth characteristics in obese Zucker rats.

Growing female obese Zucker (fa/fa) rats were treated (via intragastric gavage) for 21 d with either a (i) vehicle [corn oil; 0.9 g/kg body weight (BW)], (ii) CLA mixture [50:50; trans-10, cis-12 and cis-9, trans-11 CLA], (iii) cis-9,trans-11 CLA, or (iv) trans- 10, cis-12 CLA (CLA treatments at 1.5 g CLA/kg BW). Compared with controls, average daily gain (g/d) was reduced 24 and 44% by the CLA mixture and trans-10, cis-12 CLA, respectively. There was no treatment effect on average whole-body (minus heart and liver) composition (dry matter basis): fat (70.2%), protein (21.0%), and ash (4.3%). Compared with animals treated with cis-9,trans-11 CLA, obese Zucker rats treated with trans-10, cis-12 and the CLA mixture had 7.8% more carcass water. Treatment had no effect on heart or liver weights or on heart or liver weights as a percentage of body weight, but compared with the other treatments trans-10, cis-12 CLA increased liver lipid content by 33%. Hepatic lipid ratios of 16:1/16:0 and 18:1/18:0 (a proxy for delta9-desaturase capability) were not affected by treatment (0.1 and 0.6, respectively). Similar to previous reports, CLA increased hepatic lipid content and altered both liver and carcass FA composition (i.e., reduced arachidonic acid content), but the ability of CLA to manipulate body composition in obese Zucker rats remains questionable.

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

The fatty acid conjugated linoleic acid (CLA) and the antioxidant R-(+)-alpha-lipoic acid (R-ALA) individually enhance glucose tolerance and insulin action on skeletal muscle glucose transport in the insulin-resistant obese Zucker rat. To date, no study has assessed the potential interactions between these 2 interventions in treating insulin resistance. The present study was designed to determine whether chronic treatment with CLA and R-ALA in combination would enhance skeletal muscle glucose transport to a greater extent than either intervention individually. CLA, R-ALA, or a combination treatment of R-ALA and CLA were administered to female obese Zucker rats for 20 days at low or high doses. Whereas low-dose R-ALA (10 mg/kg body weight) alone did not alter muscle glucose transport, low-dose CLA (0.3 g/kg) induced a significant increase (38%, P <.05) in insulin-mediated glucose transport in epitrochlearis, but not in soleus. Low-dose combination therapy brought about the greatest enhancement of insulin-mediated glucose transport in epitrochlearis (77%) and soleus (54%), with the latter effect being associated with a 50% reduction in protein carbonyls (an index of tissue oxidative stress) and a 33% diminution in muscle triglycerides. High-dose treatments with CLA (1.5 g/kg), R-ALA (50 mg/kg), and the combination of CLA and R-ALA elicited increases in insulin-mediated glucose transport in epitrochlearis (57%, 58%, and 77%) and soleus (32%, 35%, and 54%). However, whereas the individual high-dose treatments with CLA and R-ALA reduced protein carbonyls (63% and 49%) and triglycerides (29% and 28%) in soleus, no further reductions were observed with the high-dose combination treatment groups. These findings support a significant interaction between low doses of CLA and R-ALA for enhancement of insulin action on skeletal muscle glucose transport, possibly via reductions in muscle oxidative stress and in lipid storage.

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

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.