Palmitate and oleate exert differential effects on insulin signalling and glucose uptake in human skeletal muscle cells

Saturated fatty acids are implicated in the development of insulin resistance, whereas unsaturated fatty acids may have a protective effect on metabolism. We tested in primary human myotubes if insulin resistance induced by saturated fatty acid palmitate can be ameliorated by concomitant exposure to unsaturated fatty acid oleate. Primary human myotubes were pretreated with palmitate, oleate or their combination for 12 h. Glucose uptake was determined by intracellular accumulation of [H-3]-2-deoxy-d-glucose, insulin signalling and activation of endoplasmic reticulum (ER) stress by Western blotting, and mitochondrial reactive oxygen species (ROS) production by fluorescent dye MitoSOX. Exposure of primary human myotubes to palmitate impaired insulin-stimulated Akt-Ser(473), AS160 and GSK-3 beta phosphorylation, induced ER stress signalling target PERK and stress kinase JNK 54 kDa isoform. These effects were virtually abolished by concomitant exposure of palmitate-treated myotubes to oleate. However, an exposure to palmitate, oleate or their combination reduced insulin-stimulated glucose uptake. This was associated with increased mitochondrial ROS production in palmitate-treated myotubes co-incubated with oleate, and was alleviated by antioxidants MitoTempo and Tempol. Thus, metabolic and intracellular signalling events diverge in myotubes treated with palmitate and oleate. Exposure of human myotubes to excess fatty acids increases ROS production and induces insulin resistance.Peer reviewe

Ameliorative effects of polyunsaturated fatty acids against palmitic acid-induced insulin resistance in L6 skeletal muscle cells

<p>Abstract</p> <p>Background</p> <p>Fatty acid-induced insulin resistance and impaired glucose uptake activity in muscle cells are fundamental events in the development of type 2 diabetes and hyperglycemia. There is an increasing demand for compounds including drugs and functional foods that can prevent myocellular insulin resistance.</p> <p>Methods</p> <p>In this study, we established a high-throughput assay to screen for compounds that can improve myocellular insulin resistance, which was based on a previously reported non-radioisotope 2-deoxyglucose (2DG) uptake assay. Insulin-resistant muscle cells were prepared by treating rat L6 skeletal muscle cells with 750 μM palmitic acid for 14 h. Using the established assay, the impacts of several fatty acids on myocellular insulin resistance were determined.</p> <p>Results</p> <p>In normal L6 cells, treatment with saturated palmitic or stearic acid alone decreased 2DG uptake, whereas unsaturated fatty acids did not. Moreover, co-treatment with oleic acid canceled the palmitic acid-induced decrease in 2DG uptake activity. Using the developed assay with palmitic acid-induced insulin-resistant L6 cells, we determined the effects of other unsaturated fatty acids. We found that arachidonic, eicosapentaenoic and docosahexaenoic acids improved palmitic acid-decreased 2DG uptake at lower concentrations than the other unsaturated fatty acids, including oleic acid, as 10 μM arachidonic acid showed similar effects to 750 μM oleic acid.</p> <p>Conclusions</p> <p>We have found that polyunsaturated fatty acids, in particular arachidonic and eicosapentaenoic acids prevent palmitic acid-induced myocellular insulin resistance.</p

Distinct breakfast patterns on satiety perception in individuals with weight excess

ABSTRACT Objectives: Western dietary pattern predisposes to weight gain, insulin resistance and cardiometabolic diseases. Promoting satiety via modifications in diet composition could be useful to fight weight gain. Mediterranean diet which is recognized to be cardioprotective contains high fiber and unsaturated fat contents. We compared the effects of distinct breakfast patterns on satiety of individuals at cardiometabolic risk, and examined the correlation of satiety level after each breakfast intervention period with glucose parameters. Materials and methods: In this 10-week cross-over clinical trial, 54 individuals with weight excess were submitted to 2 types of 4-week isocaloric breakfasts (2-week washout), one typically Brazilian and a modified one, differing concerning fiber and types of fatty acids contents. Clinical data were collected before and after each breakfast. A satiety scale was applied at fasting and 10, 30 and 120&apos; after breakfast consumption. Repeated measures ANOVA, Student t test or non-parametric correspondents were used; correlations were tested by Pearson or Spearman coefficients. Results: Anthropometric variations after breakfasts were not significant. Only after the modified breakfast, reduction in blood pressure levels was observed. The satiety level did not show significant variation across each period or between the breakfasts. Non-significant correlation between satiety and glucose, insulin and HOMA-IR values after each intervention period was observed. Conclusion: We conclude that different breakfast compositions do not alter satiety level, which is not correlated to glucose parameters in overweight individuals. Stronger modifications of daily meals might be necessary to differentiate satiety levels under distinct dietary patterns. Arch Endocrinol Metab. 2016;60(4):333-4

Palmitoleic acid (n-7) increases white adipocytes GLUT4 content and glucose uptake in association with AMPK activation

Background: Palmitoleic acid was previously shown to improve glucose homeostasis by reducing hepatic glucose production and by enhancing insulin-stimulated glucose uptake in skeletal muscle. Herein we tested the hypothesis that palmitoleic acid positively modulates glucose uptake and metabolism in adipocytes.Methods: for this, both differentiated 3 T3-L1 cells treated with either palmitoleic acid (16: 1n7, 200 mu M) or palmitic acid (16: 0, 200 mu M) for 24 h and primary adipocytes from mice treated with 16: 1n7 (300 mg/kg/day) or oleic acid (18: 1n9, 300 mg/kg/day) by gavage for 10 days were evaluated for glucose uptake, oxidation, conversion to lactate and incorporation into fatty acids and glycerol components of TAG along with the activity and expression of lipogenic enzymes.Results: Treatment of adipocytes with palmitoleic, but not oleic (in vivo) or palmitic (in vitro) acids, increased basal and insulin-stimulated glucose uptake and GLUT4 mRNA levels and protein content. Along with uptake, palmitoleic acid enhanced glucose oxidation (aerobic glycolysis), conversion to lactate (anaerobic glycolysis) and incorporation into glycerol-TAG, but reduced de novo fatty acid synthesis from glucose and acetate and the activity of lipogenic enzymes glucose 6-phosphate dehydrogenase and ATP-citrate lyase. Importantly, palmitoleic acid induction of adipocyte glucose uptake and metabolism were associated with AMPK activation as evidenced by the increased protein content of phospho(p) Thr172AMPKa, but no changes in pSer473Akt and pThr308Akt. Importantly, such increase in GLUT4 content induced by 16: 1n7, was prevented by pharmacological inhibition of AMPK with compound C.Conclusions: in conclusion, palmitoleic acid increases glucose uptake and the GLUT4 content in association with AMPK activation

Inflammatory Diseases and the Role of n-7 Unsaturated Fatty Acids as Functional Lipids

With the increasing childbearing age, the number of mothers with diabetes and gestational diabetes is escalating. Maternal hyperglycemia creates an intrauterine hyperglycemic environment via the placenta, which causes signaling abnormalities in various fetal organs due to excessive glycation. This is associated with future disease development in the child. We have shown that insulin signaling defects are induced in fetal cardiomyoblasts using a rat gestational diabetes mellitus model and cellular models. Furthermore, we reported that maternal intake of eicosapentaenoic acid (EPA), an n-3 unsaturated fatty acid, during pregnancy can ameliorate this signaling defect. However, EPA has anti-coagulant effects, and the pollution of marine fish oil, the source for EPA supplements, raises concerns about active intake by pregnant women. Recently, palmitoleic acid, an n-7 unsaturated fatty acid, garnered attention as a candidate functional lipid alternative to EPA because it has been reported to have anti-obesity, lipid metabolism improvement, and cardioprotective effects similar to those of EPA. Palmitoleic acid has cis and trans structural isomers, which differ in their food intake route and metabolism in humans. This article introduces recent findings on the biological functions of palmitoleic acid in lifestyle-related diseases and cardiovascular diseases, ranging from basic research to clinical studies

Fatty Acid Incubation of Myotubes From Humans With Type 2 Diabetes Leads to Enhanced Release of β-Oxidation Products Because of Impaired Fatty Acid Oxidation: Effects of Tetradecylthioacetic Acid and Eicosapentaenoic Acid

OBJECTIVE—Increased availability of fatty acids is important for accumulation of intracellular lipids and development of insulin resistance in human myotubes. It is unknown whether different types of fatty acids like eicosapentaenoic acid (EPA) or tetradecylthioacetic acid (TTA) influence these processes

Exploring the role of skeletal muscle in insulin resistance: lessons from cultured cells to animal models

Skeletal muscle is essential to maintain vital functions such as movement, breathing, and thermogenesis, and it is now recognized as an endocrine organ. Muscles release factors named my-okines, which can regulate several physiological processes. Moreover, skeletal muscle is particularly important in maintaining body homeostasis, since it is responsible for more than 75% of all insulin-mediated glucose disposal. Alterations of skeletal muscle differentiation and function, with subse-quent dysfunctional expression and secretion of myokines, play a key role in the pathogenesis of obesity, type 2 diabetes, and other metabolic diseases, finally leading to cardiometabolic complica-tions. Hence, a deeper understanding of the molecular mechanisms regulating skeletal muscle function related to energy metabolism is critical for novel strategies to treat and prevent insulin resistance and its cardiometabolic complications. This review will be focused on both cellular and animal models currently available for exploring skeletal muscle metabolism and endocrine func-tion