Both linoleic and α-linolenic acid prevent insulin resistance but have divergent impacts on skeletal muscle mitochondrial bioenergetics in obese Zucker rats

Abstract

The therapeutic use of polyunsaturated fatty acids (PUFA) in preserving insulin sensitivity has gained interest in recent decades; however, the roles of linoleic acid (LA) and α-linolenic acid (ALA) remain poorly understood. We investigated the efficacy of diets enriched with either LA or ALA on attenuating the development of insulin resistance (IR) in obesity. Following a 12-wk intervention, LA and ALA both prevented the shift toward an IR phenotype and maintained muscle-specific insulin sensitivity otherwise lost in obese control animals. The beneficial effects of ALA were independent of changes in skeletal muscle mitochondrial content and oxidative capacity, as obese control and ALA-treated rats showed similar increases in these parameters. However, ALA increased the propensity for mitochondrial H2O2 emission and catalase content within whole muscle and reduced markers of oxidative stress (4-HNE and protein carbonylation). In contrast, LA prevented changes in markers of mitochondrial content, respiratory function, H2O2 emission, and oxidative stress in obese animals, thereby resembling levels seen in lean animals. Together, our data suggest that LA and ALA are efficacious in preventing IR but have divergent impacts on skeletal muscle mitochondrial content and function. Moreover, we propose that LA has value in preserving insulin sensitivity in the development of obesity, thereby challenging the classical view that n-6 PUFAs are detrimental.

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

“…Unfortunately, the current study does not delineate which tissue(s) contribute to the observed improvement in whole body glucose homeostasis. However, we have previously reported in these same animals that skeletal muscle insulinstimulated Akt phosphorylation is improved following both ALA-and LA-supplemented diets, and therefore muscle is likely contributing to the observed responses (24). However, DAG was not reduced in muscle, and ALA actually increased ceramide content.…”

“…Diets supplemented with omega-3 (n-3) polyunsaturated fatty acids (PUFAs) have been shown to improve glucose tolerance (20,24,30,39); however, the majority of these past studies have examined eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3). Very little is known regarding the effects of ␣-linolenic acid (ALA, 18:3n-3); however, we have previously shown that a diet supplemented with flaxseed (i.e., rich in ALA) prevents obesityinduced insulin resistance (24).…”

“…Very little is known regarding the effects of ␣-linolenic acid (ALA, 18:3n-3); however, we have previously shown that a diet supplemented with flaxseed (i.e., rich in ALA) prevents obesityinduced insulin resistance (24). The effect of ALA on reactive lipids in diverse tissues is unknown; however, carnitine palmitoyltransferase (CPTI) has a high sensitivity for ALA-CoA moieties (9), and PUFAs in general, and ALA in particular has a high rate of oxidation within skeletal muscle (11).…”

“…However, evidence suggests that this notion is overly simplified (18). Additionally, we recently reported that a diet supplemented with safflower [i.e., rich in linoleic acid (LA, 18:2n-6)] protected against obesityinduced insulin resistance (24). The mechanism-of-action involved in LA-mediated improvements in insulin sensitivity, and the potential alterations in reactive lipid profiles in key insulin sensitizing tissues following LA consumption, remain unknown.…”

The Preparation of Hyaluronic Acid Nanoparticles from Aspicilia lichens Using Bifido Bacteria for Help in the Treatment of Diabetes in Rats In Vivo

“…In previous studies, the secondary metabolites of lichens, including dibenzofuran, depside, depsidon, and derivatives of benzoic acid such as usnic acid, atranorin, sekikaic acid, and methyl orselinate, have been studied. In the current study, secondary metabolite compounds produced by lichens of Aspicilia , including usnic acid, derivatives of benzoic acid, terpenes, and fatty acids such as oleic acid (Coll et al ., ), linoleic acid (Matravadia et al ., ), stearic acid (Reeves, ), palmitoleic acid, pyrocatechin (polyphenol), stigmastrol, campesterol, and taraxasterol (phytoesterol), have been identified in Aspicilia lichens. All of them have applications in the treatment of diabetes in vivo (Figs and ).…”