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

Molecular System Bioenergetics—New Aspects of Metabolic Research

This Special Issue is a significant step in developing a new direction of metabolic research— Molecular System Bioenergetics, which itself is a part of Systems Biology. As a new paradigm of biological sciences, Systems Biology aims at understanding of biological functions by studies and description of new, system level properties, resulting from interactions between components of biological systems at any level of organization, from molecular to population. Metabolism is the way of life of cells by exchanging mass and energy with the surrounding medium, and understanding its mechanisms requires knowledge of the complex interactions between cellular systems and components. While studies of metabolism have a long history, new concepts of Systems Biology provide useful tools for metabolic research. According to Schrödinger, living cells need to be open systems with energy and mass exchange with the surrounding medium, with the aim of maintaining their high structural and functional organization and thus their internal entropy low, achieving this by means of increasing the entropy of the medium by catabolic reactions. Thus, Schrödinger wrote: “The essential thing in metabolism is that the organism succeeds in freeing itself from all entropy it cannot help producing while alive”. Thus, free energy conversion in the cells is an important, central part of metabolism, and understanding the complex mechanisms of its regulation is the aim of Molecular System Bioenergetics. In this Special Issue, several important problems in this field were analyzed

Caractérisation du métabolisme protéino-énergétique musculaire au cours de la cachexie cardiaque

Numéro national de thèse : 2006CLF1MS30 Diplôme : Dr. d'UniversiteL'IC évolue dans 16% des cas vers un état de dénutrition nommé cachexie cardiaque. Nous souhaitons étudier la protéosynthèse et l'activité ATPasique de la myosine de différents types musculaires durant la cachexie cardique. Un IDM a été réalisé chez 10 rates. Les animaux ayant maigri de plus de 7,5% sont considérés comme cachectiques cardiaques et sacrifiés simultanément à un groupe contrôle après injection sous-cutanée de [13C]Valine. Deux mL de sang ainsi que les muscles soleus, gastrocnemus, tibialis anterior, le coeur, le foie et le tissu adipeux péri-rénal sont prélevés et pesés. Les AA circulants, ainsi qu'un bilan glucido-lipidique sont dosés dans le sang. Les protéines des différents prélèvements tissulaires sont extraites puis séparées selon leur compartiment cellulaire par centrifugation. Le FSR (%/hr) mitochondrial est calculé à partir du taux d'incorporation en valine du pool précurseur d'AA et des protéines mitochondriales, mesuré en spectrométrie de masse. Enfin, les activités enzymatiques de la citrate synthase, de la cytochrome c oxydase et de l'ATPase de la myosine sont mesurées par absorptiomètrie. Résultats : 60% des rates ayant subi l'IDM sont devenues cachectique. L'aimaigrissement est de 25%. Les résultats plasmatiques retrouvent une élévation des TG, du lactate et des AA dans le groupe CC par rapport au groupe C. Le poids des muscles soleus, gastrocnemus et du tissu adipeux sont inférieurs. Le FSR mitochondrial du soleus est plus élevé dans le groupe CC que le C. Les activités COX et ATPase de la myosine sont diminuées dans le groupe CC par rapport au groupe C. Cette étude confirme qu'il existe durant la CC de profondes altérations du métabolisme protéique notamment mitochondrial associées à des mécanismes de compensation physiologique qui se traduisent par une augmentation de la protéosynthèse mitocondriale

Toward an Integrated Consideration of 24 h Movement Guidelines and Nutritional Recommendations

While physical activity, sleep and sedentary behaviors are almost always considered independently, they should be considered as integrated human behaviors. The 24 h Movement approach proposes a concomitant consideration of these behaviors to promote overall health. Not only do these behaviors impact energy expenditure, but they have also been shown to separately impact energy intake, which should be further explored when considering the entire integration of these movement behaviors under the 24 h movement approach. After an evaluation of the prevalence of meeting the 24 h Movement and dietary recommendations, this review summarizes the available evidence (using English publications indexed in PubMed/MEDLINE) regarding the association between the 24 h Movement Guidelines and eating habits. Altogether, the results clearly show the beneficial impact of promoting the 24 h guidelines simultaneously, highlighting that the higher the number of respected movement recommendations, the better eating behaviors in both children and adults. Importantly, our results point out the importance of emphasizing the need to reach sedentary guidelines for better eating habits. Movement and dietary behaviors appear closely related, and giving recommendations on one might impact the other. Combining the 24 h Movement with dietary Guidelines might be more efficient than promoting them separately in public health strategies

Mitochondrial protein synthesis is increased in oxidative skeletal muscles of rats with cardiac cachexia

International audienceSince cardiac cachexia could be associated with alterations in muscular mitochondrial metabolism, we hypothesized that the expected alterations in the activities of mitochondrial oxidative enzymes could be associated with changes in mitochondrial protein synthesis in oxidative skeletal muscles. Cardiac cachexia was provoked in male rats by the ligation of the left coronary artery. Six cachectic and 6 control rats were age-paired, and their food intake was observed. The synthesis of mitochondrial proteins was measured by [1-13C]-valine infusion in soleus, tibilais, myocardium, and liver. Muscles (soleus, gastrocnemius, and tibialis anterior), heart, kidneys, liver, and visceral adipose tissue were weighed. Mitochondrial cytochrome c oxydase IV as well as citrate synthase and myosin ATPase activities were measured. As expected, decreased food intake was observed in the cachectic group. Heart, kidney, and liver weights were higher in the cachectic group, while the visceral adipose tissue weight was lower (P < .01). No changes in muscle weights were observed. Soleus mitochondrial proteins fractional synthesis rate was higher in the cachectic group (P = .054). Cytochrome c oxydase IV activity was reduced (P = .009) and increased (P = .038) in the soleus and liver of the cachectic rats, respectively. No change in citrate synthase activity was observed. Myosin ATPase activity was reduced in the gastrocnemius of the cachectic group (P < .01). Mitochondrial protein synthesis is increased in the soleus of rats with cardiac cachexia, suggesting a compensatory mechanism of the impaired oxidative mitochondrial function. Further work should assess whether the mitochondrial protein synthesis is altered in chronic heart failure patients with cardiac cachexia, and whether this is the cause or the consequence of cachexia

Weight regain, body composition, and metabolic responses to weight loss in weight cycling athletes: A systematic review and meta‐analyses

International audienceAbstract Depending on the nature of their sports, athletes may be engaged in successive weight loss (WL) and regain, conducing to “weight cycling.” The aims of this paper were to systematically (and meta‐analytically when possible) analyze the post‐WL recovery of (i) body weight and (ii) fat mass; fat‐free mass; and performance and metabolic responses in weight cycling athletes (18–55 years old, body mass index < 30 kg.m −2 ). MEDLINE, Embase, and SPORTDiscus databases were explored. The quality and risk of bias of the 74 included studies were assessed using the quality assessment tool for quantitative studies. Thirty‐two studies were eligible for meta‐analyses. Whatever the type of sports or methods used to lose weight, post‐WL body weight does not seem affected compared with pre‐WL. While similar results are observed for fat‐free mass, strength sports athletes (also having longer WL and regain periods) do not seem to fully recover their initial fat mass (ES: −0.39, 95% CI: [−0.77; −0.00], p = 0.048, I 2 = 0.0%). Although the methods used by athletes to achieve WL might prevent them from a potential post‐WL fat overshooting, further studies are needed to better understand WL episodes consequences on athletes' performance as well as short‐ and long‐term physical, metabolic, and mental health

Chronological approach of diet-induced alterations in muscle mitochondrial functions in rats

International audienceOBJECTIVE: Mitochondrial dysfunction might predispose individuals to develop insulin resistance. Our objective was to determine whether mitochondrial dysfunction or insulin resistance was the primary event during high-fat (HF) diet. RESEARCH METHODS AND PROCEDURES: Rats were fed an HF diet for 0, 3, 6, 9, 14, 20, or 40 days and compared with control. Soleus and tibialis muscle mitochondrial activity were assessed using permeabilized fiber technique. Insulin [area under the curve for insulin (AUC(I))] and glucose [area under the curve for glucose (AUC(G))] responses to intraperitoneal glucose tolerance test as well as fasting plasma non-esterified fatty acids (NEFAs), triglyceride, and glycerol concentrations were determined. RESULTS: AUC(I) and AUC(G) were altered from Day 6 (p < 0.01 vs. Day 0). In soleus, oxidative phosphorylation (OXPHOS) activity was transiently enhanced by 26% after 14 days of HF diet (p < 0.05 vs. Day 0) conjointly with 62% increase in NEFA concentration (p < 0.05 vs. Day 0). This was associated with normalized AUC(G) at Day 14 and with a decline of plasma NEFA concentration together with stabilization of intra-abdominal adiposity at Day 20. Prolongation of HF diet again caused an increase in plasma NEFA concentration, intra-abdominal adiposity, AUC(I), and AUC(G). At Day 40, significant decrease in OXPHOS activity was observed in soleus. DISCUSSION: Mitochondria first adapt to overfeeding in oxidative muscle limiting excess fat deposition. This potentially contributes to maintain glucose homeostasis. Persistent overfeeding causes insulin resistance and results in a slow decline in oxidative muscle OXPHOS activity. This shows that the involvement of mitochondria in the predisposition to insulin resistance is mainly due to an inability to face prolonged excess fat delivery