LA and ALA prevent glucose intolerance in obese male rats without reducing reactive lipid content, but cause tissue-specific changes in fatty acid composition

Abstract

While the cause of Type 2 diabetes remains poorly defined, the accumulation of reactive lipids within white adipose tissue, skeletal muscle, and liver have been repeatedly implicated as underlying mechanisms. The ability of polyunsaturated fatty acids (PUFAs) to prevent the development of insulin resistance has gained considerable interest in recent years; however, the mechanisms-of-action remain poorly described. Therefore, we determined the efficacy of diets supplemented with either linoleic acid (LA) or α-linolenic acid (ALA) in preventing insulin resistance and reactive lipid accumulation in key metabolic tissues of the obese Zucker rat. Obese Zucker rats displayed impaired glucose homeostasis and reduced n-3 and n-6 PUFA content in the liver and epididymal white adipose tissue (EWAT). After the 12-wk feeding intervention, both LA- and ALA-supplemented diets prevented whole body glucose and insulin intolerance; however, ALA had a more pronounced effect. These changes occurred in association with n-3 and n-6 accumulation in all tissues studied, albeit to different extents (EWAT > liver > muscle). Triacylglycerol (TAG), diacylglycerol (DAG), ceramide, and sphingolipid accumulation were not attenuated in obese animals supplemented with either LA or ALA, suggesting that preservation of glucose homeostasis occurred independent of changes in reactive lipid content. However, PUFA-supplemented diets differentially altered the fatty acid composition of TAGs, DAGs, and PLs in a tissue-specific manner, suggesting essential fatty acid metabolism differs between tissues. Together, our results indicate that remodeling of the fatty acid composition of various lipid fractions may contribute to the improved glucose tolerance observed in obese rats fed PUFA-supplemented diets.

α‐Linolenic acid and exercise training independently, and additively, decrease blood pressure and prevent diastolic dysfunction in obese Zucker rats

“…In accordance with previous findings (Matravadia et al . ), all animals being supplemented with ALA had significantly decreased levels of n ‐6 fatty acids (LA and AA) and significantly increased levels of n ‐3 fatty acids (ALA, EPA and DHA) in total FFA (Fig. A ), thus validating the effectiveness of our dietary intervention.…”

Essential Fatty Acids Linoleic Acid and α‐Linolenic Acid Sex‐Dependently Regulate Glucose Homeostasis in Obesity

“…It seems that the essential fatty acids LA and ALA could not ameliorate obesity development and inflammation, and even induce IR in mice . For the treatment of obesity already established, nonetheless, both ALA and LA could rescue impaired glucose homeostasis in obese male rats with no changes in reactive lipid content . Current study reported that ALA and LA sex‐dependently reversed obesity‐induced IR in DIO male and female mice, respectively.…”

Priming Effect of a Morning Meal on Hepatic Glucose Disposition Later in the Day

“…Chronic consumption of a high-ALA diet in mice fed a high-fat diet was associated with reduced hepatic glucose production, in association with lower levels of steatosis (30). Also, oral and intravenous glucose tolerance were modestly improved in Zucker diabetic fatty rats fed a high-ALA diet for 8 weeks, although this was not associated with altered expression of any of the hepatic inflammatory markers examined (31). The acute effect of changes in hepatic ALA have not, to our knowledge, been examined.…”