Aims/hypothesis Intramyocellular lipids (IMCL) accumulation is a classical feature of metabolic diseases. We hypothesised that IMCL accumulate mainly as a consequence of increased adiposity and independently of type 2 diabetes. To test this, we examined IMCL accumulation in two different models and four different populations of participants: muscle biopsies and primary human muscle cells derived from non-obese and obese participants with or without type 2 diabetes. The mechanism regulating IMCL accumulation was also studied. Methods Muscle biopsies were obtained from ten non-obese and seven obese participants without type 2 diabetes, and from eight non-obese and eight obese type 2 diabetic patients. Mitochondrial respiration, citrate synthase activity and both ON, Canada Diabetologia (2010) 53:1151-1163 DOI 10.1007/s00125-010-1708 accumulation is dependent upon obesity or type 2 diabetes and is related to sarcolemmal FAT/CD36 relocation. In cultured myotubes, IMCL content and FAT/CD36 relocation are independent of type 2 diabetes, suggesting that distinct factors in obesity and type 2 diabetes contribute to permanent FAT/CD36 relocation ex vivo.

Key points• Prolonged obesity leads to ectopic lipid accumulation in non-adipose tissues, particularly in skeletal muscles, inducing metabolic dysfunctions (reduced glucose uptake, mitochondria dysfunction, lipotoxicity).• Several studies in humans and rodents have shown that obesity induces a short-term increase in fat-free mass but a long-term decrease in skeletal muscle mass.• We investigated the mechanisms potentially involved in muscle loss by measuring simultaneously protein synthesis and lipid infiltration in different types of skeletal muscles, during the development of obesity.• Our results show that protein synthesis rate in glycolytic muscles increased together with muscle mass during the early phase of obesity development, whereas it decreased later. Reduced protein synthesis rate was associated with a high lipid accumulation in glycolytic muscles.• These results suggest that lipid accumulation in muscles during prolonged obesity is deleterious for amino acid incorporation in skeletal muscle proteins, and thus indirectly for muscle mass.Abstract The object of the study was to investigate the sequential changes of protein synthesis in skeletal muscle during establishment of obesity, considering muscle typology. Adult Wistar rats were fed a standard diet for 16 weeks (C; n = 14), or a high-fat, high-sucrose diet for 16 (HF16; n = 14) or 24 weeks (HF24; n = 15). Body composition was measured using a dual-energy X-ray absorptiometry scanner. The fractional synthesis rates (FSRs) of muscle protein fractions were calculated in tibialis anterior (TA) and soleus muscles by incorporation of L-13 C-valine in muscle protein. Muscle lipid and mitochondria contents were determined using histochemical analysis. Obesity occurred in an initial phase, from 1 to 16 weeks, with an increase in weight (P < 0.05), fat mass (P < 0.001), muscle mass (P < 0.001) and FSR in TA (actin: 5.3 ± 0.2 vs. 8.8 ± 0.5% day −1 , C vs. HF16, P < 0.001) compared with standard diet. The second phase, from 16 to 24 weeks, was associated with a weight stabilization, a decrease in muscle mass (P < 0.05) and a decrease in FSR in TA (mitochondrial: 5.6 ± 0.2 vs. 4.2 ± 0.4% day −1 , HF16 vs. HF24, P < 0.01) compared with HF16 group. Muscle lipid content was increased in TA in the second phase of obesity development (P < 0.001). Muscle mass, lipid infiltration and muscle protein synthesis were differently affected, depending on the stage of obesity development and muscle typology. Chronic lipid infiltration in glycolytic muscle is concomitant with a reduction of muscle protein synthesis, suggesting that muscle lipid infiltration in response to a high-fat diet is deleterious for the incorporation of amino acid in skeletal muscle proteins.

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Training-induced improvement in lipid oxidation in type 2 diabetes mellitus is related to alterations in muscle mitochondrial activity. Effect of endurance training in type 2 diabetes.. Diabetes and Metabolism, Elsevier Masson, 2008, 34 (2) AbstractAim: We investigated in type 2 diabetic patients (T2D) if an individualized training effect on whole body lipid oxidation is associated with changes in muscle oxidative capacities.Methods: Eleven T2D participated in this study. Whole body lipid oxidation during exercise was assessed by graded exercise indirect calorimetry. Blood samples for measuring blood glucose and free fatty acids during exercise and muscle oxidative capacities measured from a skeletal muscle biopsy (i.e., mitochondrial respiration and citrate synthase activity) were investigated in T2D before and after a 10-week individualized training targeted at LIPOXmax, which corresponds to the power at which the highest rate of lipids is oxidized (lipid oxidation at LIPOXmax).Results: Training induced both a shift to a higher power intensity of LIPOXmax (+9.1 ± 4.2 Watts, P<0.05) and an improvement of lipid oxidation at LIPOXmax (+51.27 ± 17.93 mg.min -1 , P<0.05). The improvement in lipid oxidation was correlated with training-induced improvement of mitochondrial respiration (r=0.78, P<0.01) and citrate synthase activity (r=0.63, P<0.05).Conclusion: This study shows that a quite moderate training protocol targeted at the LIPOXmax in T2D mellitus improves the ability to oxidize lipids during exercise, and that this improvement is associated with an enhancement of muscle oxidative capacities.

BackgroundBecause abdominal obesity is predisposed to various metabolic disorders, it is of major importance to assess and track the changes with time of this specific fat mass. The main issue for clinicians or researchers is to use techniques for assessing abdominal fat deposition and its accumulation or changes over time, without sacrificing of experimental subjects. In the rat, techniques to investigate in-vivo visceral fat mass are lacking. The purpose of the study was to validate indirect Dual-energy X-ray Absorptiometry technique and abdominal circumference measurement as tools to predict visceral adipose tissue in rats.Forty-three Wistar male rats from different body weight, fat mass and ages were included in the study. Visceral fat mass was assessed by weighing the total perirenal and peri-epididymal adipose tissues after dissection. Statistical methods were used to discriminate the best region of interest allowing the in-vivo measure of Central Fat Mass by DXA. Abdominal circumference was measured at the same time as the DXA scan.ResultsA region of interest including Central Fat Mass from the whole body DXA scan (extending from L2 to L5 vertebrae), correlated strongly with ex-vivo Fat Mass (r = 0.94, p < 0.001). Abdominal circumference correlated significantly with ex-vivo Fat Mass (r = 0.82, p < 0.001) and Central Fat Mass (0.90, p < 0.001) in the whole group of rats. When dividing the whole group into lean and fat rats, correlations remained significant between Central Fat Mass and ex-vivo Fat Mass but disappeared for the lean group between abdominal circumference and ex-vivo Fat Mass.ConclusionsThis study validates the Central Fat Mass determined by DXA as a non-sacrificial technique to assess visceral fat for in-vivo investigations in rats. The abdominal circumference measure appears useful in studying overweight or obese rats. These two techniques could be convenient tools in follow-up and longitudinal studies.

High-intensity interval training (HIIT) has been suggested as an effective alternative to traditional moderate-intensity continuous training (MICT) that can yield improvements in a variety of health outcomes. Yet, despite the urgent need to find effective strategies for the treatment of pediatric obesity, only a few studies have addressed the impact of HIIT on eating behaviors and body composition in this population. This study aimed to compare the effect of HIIT versus MICT on eating behaviors in adolescents with obesity and to assess if the participants’ baseline dietary status is associated with the success of the intervention. Forty-three adolescents with obesity were randomly assigned to a 16-week MICT or HIIT intervention. Body composition and 24-h ad libitum energy intake were assessed at baseline and at the end of the program. Restrained eating, emotional eating, and external eating were assessed using the Dutch Eating Behavior Questionnaire at baseline. Both interventions led to significant weight, body mass index (BMI), and fat mass percentage (FM%) reductions, with better improvements in FM% in the HIIT group; whereas 24-h ad libitum energy intake increased to a similar extent in both groups. HIIT provides better body composition improvements over MICT, despite a similar increase in energy intake. Restrained eaters experienced less weight loss and smaller BMI reduction compared with unrestrained eaters; higher baseline cognitively restrained adolescents showed a greater increase of their ad libitum energy intake. Novelty HIIT favors better body composition improvements compared with MICT. Both MICT and HIIT increased ad libitum energy intake in adolescents with obesity. Weight loss achievement is better among unrestrained eaters.

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