Potential Mechanisms of Muscle Mitochondrial Dysfunction in Aging and Obesity and Cellular Consequences

Mitochondria play a key role in the energy metabolism in skeletal muscle. A new concept has emerged suggesting that impaired mitochondrial oxidative capacity in skeletal muscle may be the underlying defect that causes insulin resistance. According to current knowledge, the causes and the underlying molecular mechanisms at the origin of decreased mitochondrial oxidative capacity in skeletal muscle still remain to be elucidated. The present review focuses on recent data investigating these issues in the area of metabolic disorders and describes the potential causes, mechanisms and consequences of mitochondrial dysfunction in the skeletal muscle

ALA, EPA and DHA differentially Modulate Palmitate-induced Lipotoxicity through Alterations of its Metabolism and Storage in C12C12 Muscle Cells

On that occasion, the two French societies dedicated to lipid science and technology, GERLI and SFEL, will combine their efforts to assist the scientific committee to establish an attractive program for the Euro Fed Lipid congress.Since few decades, incidence of obesity and type 2 diabetes (T2D) is increasing. Excessive intake of energy leads to fat overload and formation of lipotoxic compounds mainly derived from the saturated fatty acid palmitate in insulin-sensitive tissues (muscle, liver and white adipose tissue), promoting insulin resistance (IR, a well-known metabolic disorder in T2D). Supplementation with n-3 fatty acids (n-3FA) is suggested to reduce lipotoxicity and IR. We hypothesized that, according to the n-3FA used, differential and specific effects on palmitate metabolism in muscle cells will be demonstrated. C2C12 myotubes were treated with 500 µM of palmitate without or with 50 µM of alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) for 16 hours and collected for measurement of membrane fluidity using diphenyl-hexatriene, ceramide content, insulin-dependent Akt protein phosphorylation (as an index of IR). The assessment of the intracellular metabolism and incorporation of palmitate into lipid fractions (triglycerides, phospholipids, diglycerides) was performed after treatment for 3 hours with [1-14C]-palmitate. As expected, palmitate-induced IR was restored by EPA and DHA supplementation whereas ALA had no effect compared to palmitate alone. EPA and DHA significantly improved C2C12 membrane fluidity compared to palmitate alone (+8.5% and +13% respectively, p<0.05). Furthermore, palmitate incorporation into the diglyceride fraction was decreased by 31 and 47% by EPA and DHA vs. palmitate, respectively (p=0.05). However, DHA significantly increased the ratio of diglycerides to total lipids vs. palmitate alone (p<0.05), whereas EPA did not. Finally, EPA was more potent to decrease palmitate-induced ceramide accumulation (+174%, p<0.05 vs. control) compared to DHA (-50% and -29% repectively, p<0.05). In conclusion and contrary to ALA, EPA and DHA treatment improved the insulin signalling pathway by differently modulating membrane fluidity and lipid and palmitate metabolism, thus demonstrating that n-3FA have different metabolic impacts on C2C12 lipid metabolism

Differential impact of milk fatty acid profiles on cardiovascular risk biomarkers in healthy men and women

International audienceObjectives: to evaluate the impact of three specific ruminant (R) milk fats resulting from modification of the cow's diet on cardiovascular risk factors in healthy volunteers. R-milk fats were characterized by increased content in total trans fatty acids (R-TFA) and parallel decrease in saturated fatty acids (SFA). Methods: 111 healthy, normolipemic men and women have been recruited for a monocentric, randomised, double-blind, and parallel intervention, 4-week controlled study. Volunteers consumed 3 experimental products (butter, dessert cream and cookies) made with one of the 3 specific milk fats (55 g fat/day). During the first week (run-in period), the subjects consumed on a daily basis dairy products containing 72% SFA/2.85% R-TFA (called "L0"). For the next 3 weeks of the study (intervention period), the first group continued to consume L0 products. The second group received dairy products containing 63.3% SFA/4.06% R-TFA (called "L4"), and the third group received dairy products containing 56.6% SFA/12.16% R-TFA (called "L9"). Results: plasma concentrations of HDL-cholesterol was not significantly altered by either diet (p = 0.38). Compared to L0 diet, L4 diet contributed to reduce LDL-cholesterol (-0.140.38 mmol/L, p= 0.04), total cholesterol (-0.130.50 mmol/L, p = 0.04), LDL-cholesterol/HDL-cholesterol (-0.140.36, p = 0.03) and total cholesterol/HDL-cholesterol (-0.180.44, p = 0.02). Conclusion: different milk fat profiles can change cardiovascular plasma parameters in human healthy volunteers. A limited increase of the R-TFA/SFA ratio in dairy products is associated with an improvement in some cardiovascular risk factors. However, a further increase in R-TFA/SFA ratio has no additional benefit

Effets comparatifs des acides gras omega-3 (ALA, EPA, DHA) sur la sensibilité à l’insuline des cellules musculaires C2C12 dans un contexte lipotoxique

Objectifs :Etudier le rôle des ω3 sur la lipotoxicité induite par l’acide gras saturé palmitate (PAL, C16:0) dans un modèle de cellule musculaire C2C12.Identifier les effets propres de chaque w3 (ALA, EPA et DHA) à dose équivalente sur la fluidité des membranes et la réponse à l’insuline.Suivre le devenir intracellulaire du [1-14C]-palmitate en présence d’un w3 et définir les classes de lipides altérées.Rechercher les voies de signalisation impliquées dans la modulation de la réponse à l’insuline

Mitochondrial dysfunction results from oxidative stress in the skeletal muscle of diet-induced insulin-resistant mice.

International audienceMitochondrial dysfunction in skeletal muscle has been implicated in the development of type 2 diabetes. However, whether these changes are a cause or a consequence of insulin resistance is not clear. We investigated the structure and function of muscle mitochondria during the development of insulin resistance and progression to diabetes in mice fed a high-fat, high-sucrose diet. Although 1 month of high-fat, high-sucrose diet feeding was sufficient to induce glucose intolerance, mice showed no evidence of mitochondrial dysfunction at this stage. However, an extended diet intervention induced a diabetic state in which we observed altered mitochondrial biogenesis, structure, and function in muscle tissue. We assessed the role of oxidative stress in the development of these mitochondrial abnormalities and found that diet-induced diabetic mice had an increase in ROS production in skeletal muscle. In addition, ROS production was associated with mitochondrial alterations in the muscle of hyperglycemic streptozotocin-treated mice, and normalization of glycemia or antioxidant treatment decreased muscle ROS production and restored mitochondrial integrity. Glucose- or lipid-induced ROS production resulted in mitochondrial alterations in muscle cells in vitro, and these effects were blocked by antioxidant treatment. These data suggest that mitochondrial alterations do not precede the onset of insulin resistance and result from increased ROS production in muscle in diet-induced diabetic mice

The 24-h Energy Intake of Obese Adolescents Is Spontaneously Reduced after Intensive Exercise: A Randomized Controlled Trial in Calorimetric Chambers

Background: Physical exercise can modify subsequent energy intake and appetite and may thus be of particular interest in terms of obesity treatment. However, it is still unclear whether an intensive bout of exercise can affect the energy consumption of obese children and adolescents. [br/] Objective: To compare the impact of high vs. moderate intensity exercises on subsequent 24-h energy intake, macronutrient preferences, appetite sensations, energy expenditure and balance in obese adolescent. [br/] Design: This randomized cross-over trial involves 15 obese adolescent boys who were asked to randomly complete three 24-h sessions in a metabolic chamber, each separated by at least 7 days: (1) sedentary (SED); (2) Low-Intensity Exercise (LIE) (40% maximal oxygen uptake, VO(2)max); (3) High-Intensity Exercise (HIE) (75% VO(2)max). Results: Despite unchanged appetite sensations, 24-h total energy intake following HIE was 6-11% lower compared to LIE and SED (p<0.05), whereas no differences appeared between SED and LIE. Energy intake at lunch was 9.4% and 8.4% lower after HIE compared to SED and LIE, respectively (p<0.05). At dinner time, it was 20.5% and 19.7% lower after HIE compared to SED and LIE, respectively (p<0.01). 24-h energy expenditure was not significantly altered. Thus, the 24-h energy balance was significantly reduced during HIE compared to SED and LIE (p<0.01), whereas those of SED and LIE did not differ. [br/] Conclusions: In obese adolescent boys, HIE has a beneficial impact on 24-h energy balance, mainly due to the spontaneous decrease in energy intake during lunch and dinner following the exercise bout. Prescribing high-intensity exercises to promote weight loss may therefore provide effective results without affecting appetite sensations and, as a result, food frustrations

Snacking et rythmes alimentaires : évolutions et perceptions chez les Français. Synthèse du workshop de la SFN en partenariat avec Mondelez donné en visioconférence le mardi 12 octobre 2021

International audienc

Effets du vieillissement et de l'activité physique sur la capacité mitochondriale du muscle à oxyder les acides gras (implication dans le contrôle de la balance lipidique et de la sensibilité à l'insuline chez l'homme)

CLERMONT FD-BCIU-Santé (631132104) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Fat and protein redistribution with aging : Metabolic considerations

Suppl 3International audienc

Alterations in glycine metabolism in obesity and chronic metabolic diseases – an update on new advances

Purpose of reviewThe metabolic signature associated with obesity is characterized by a decrease in plasma glycine concentration, a feature closely associated with insulin resistance and highly predictive of the risk of developing chronic metabolic diseases. This review presents recent advances in understanding the causes of decreased glycine availability and in targeting strategies to replenish the glycine pool and especially to improve insulin resistance.Recent resultsRecent literature has made progress in understanding host and gut microbiota mechanisms in determining circulating glycine levels. It has also explored new clinical pathways to restore circulating glycine levels and insulin resistance in obesity-related metabolic diseases.Recent findings suggest that glycine metabolism must now be considered in close interaction with branched-chain amino acid (BCAA) metabolism. Thus, strategies that decrease BCAAs seem to be the best to restore glycine. Furthermore, recent literature has confirmed that lifestyle strategies aimed at inducing weight loss are effective in replenishing the glycine pool. It also confirms that correcting the dysbiosis of the gut microbiota associated with obesity may be a valuable means of achieving this goal. However, it remains unclear whether dietary glycine is an effective strategy for correcting cardiometabolic disorders in obesity