Effects of trans MUFA from dairy and industrial sources on muscle mitochondrial function and insulin sensitivity

Abstract

Epidemiological studies suggest that chronic consumption of trans MUFA may alter muscle insulin sensitivity. The major sources of dietary trans MUFA (dairy fat vs. industrially hydrogenated oils) have different isomeric profiles and thus probably different metabolic consequences. These effects may involve alterations in muscle mitochondrial oxidative capacity, which may in turn promote insulin resistance if fatty acid oxidation is reduced. We report that in Wistar rats, an 8 week diet enriched (4% of energy intake) in either dairy, industrial, or control MUFA did not alter insulin and glucose responses to an intraperitoneal glucose tolerance test (1g/kg). In C2C12 myotubes, vaccenic and elaidic acids did not modify insulin sensitivity compared with oleic acid. Furthermore, the ex vivo total, mitochondrial and peroxisomal oxidation rates of [1-14 C]oleic, vaccenic, and elaidic acids were similar in soleus and tibialis anterior rat muscle. Finally, an 8 week diet enriched in either dairy or industrial trans MUFA did not alter mitochondrial oxidative capacity in these two muscles compared with control MUFA but did induce a specific reduction in soleus mitochondrial ATP and superoxide anion production (P , 0.01 vs. control). In conclusion, dietary trans MUFA of dairy or industrial origin have similar effects and do not impair muscle mitochondrial capacity and insulin sensitivity. Plurimetabolic syndrome (syndrome X) affects 40% of men and 25% of women over the age of 55 in Europe (1). One of the features of this metabolic disorder is impaired insulin sensitivity 10 to 20 years before the development of type 2 diabetes, with a concomitant increased risk of cardiovascular disease (2). Several observational studies suggest that insulin resistance is primarily a lifestyle disorder (3), because overweight and low physical activity are the greatest risk factors for type 2 diabetes (4). Evidence is now emerging that the incidence of this metabolic disorder could also be affected by diet composition. High energy intake is a factor contributing to the development of insulin resistance by increasing body weight and fat deposition (5, 6), whereas several studies have shown that weight loss is very effective in reducing the prevalence of type 2 diabetes in overweight individuals (7,8). Among all the macronutrients, dietary fatty acids have received particular attention as potential inductors of insulin resistance. Changes in the fatty acid composition of blood and muscle have been shown to correlate with insulin resistance in humans (9, 10). Furthermore, epidemiological studies have reported that mono-and polyunsaturated fat may reduce the risk of developing type 2 diabetes, whereas saturated fat has been reported to have a potentially adverse effect (11-13). These effects are independent of changes in body weight and composition. The KANWU (Kuopio, Aarhus, Naples, Wollong and Uppsala) interventional study confirms these effects, but only when total dietary fat consumption is lower than 37% of total energy intake (14)....

Trans fatty acids and weight gain

“…The majority of the studies performed using rodent models have reported that diets containing TFA have resulted in the same or lower body weights than control diets containing cis FA. 18,20,21,23,24,26 However, the two studies that measured hormones associated with appetite and weight gain reported lower leptin 21,23 and higher adiponectin and resistin levels 21 in animals fed diets containing 4.5 or 20% TFA than animals on cis MUFA-based control diets, despite there being no differences in weight between groups. Leptin, adiponectin and resistin are hormones secreted by adipose tissue.…”

“…There were no differences in total body weight or weight of intraabdominal adipose tissue in groups of Wistar rats fed diets containing 4% of E from ruminant TFA, industrial TFA or oleic acid for 8 weeks. 24 There were also no differences in food intake or weight gain in groups of lean and obese JCR:LA-cp rats fed diets with and without 1.5% (wt wt À1 ) vaccenic acid (the predominant TFA in ruminant sources 25 ) for 3 26 or 16 weeks. 27 Diets containing partially hydrogenated vegetable oil (1.05% of E from TFA), palm, canola or soy oil were fed to lactating female rats and then to their weaned male offspring until the males were 45 days old.…”

Ruminant and industrial sources of trans-fat and cardiovascular and diabetic diseases

“…Thus, any TFA-induced alteration in muscle metabolism is not due to differences in oxidation rates (30) .…”

“…To go further in the comprehension of the mechanisms, Tardy et al established in C2C12 myotubes that insulinstimulated Akt phosphorylation was similar to the control group (without fatty acid) after incubation with oleic, elaidic and vaccenic acids (30) , suggesting no direct effect of TFA on muscle insulin pathways. Those results were reinforced by a recent study of Hommelberg et al (34) which demonstrated in cultured murine skeletal muscle cells that insulin-stimulated glucose uptake and GLUT4 translocation were similar to those in the control group after incubation with vaccenic and elaidic acids.…”

Evaluation of Mitochondrial Functions and Dysfunctions in Muscle Biopsy Samples

“…This technique uses a radiolabelled [1 or U-14 C] fatty acid (such as oleate or palmitate for the most commons) bound to albumin at the ratio 4.5:1 (Morio et al, 2001;Rimbert et al, 2004;Tardy et al, 2008). A detailed procedure is provided in supplementary materials.…”