Aurélie Masgrau

Impaired protein metabolism: interlinks between obesity, insulin resistance and inflammation

Metabolic and structural changes in skeletal muscle that accompany obesity are often associated with the development of insulin resistance. The first events in the pathogenesis of this disorder are considered as an accumulation of lipids within skeletal muscle due to blunted muscle capacity to oxidize fatty acids. Fat infiltration is also associated with muscle fibre typology modification, decrease in muscle mass and impairments in muscle strength. Thus, as a result of obesity, mobility and quality of life are affected, and this is in part due to quantitative and qualitative impairments in skeletal muscle. In addition, the insulin resistance related to obesity results not only in defective insulin‐stimulated glucose disposal but has also detrimental consequences on protein metabolism at the skeletal muscle level and whole‐body level. This review highlights the involvement of fat accumulation and insulin resistance in metabolic disorders occurring in skeletal muscle during the development of obesity, and the impairments in the regulation of protein metabolism and protein turnover in the links between obesity, metabolic inflammation and insulin resistance.

Time-course changes of muscle protein synthesis associated with obesity-induced lipotoxicity

•  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.

Impact of an obesogenic diet program on bone densitometry, micro architecture and metabolism in male rat

BackgroundThe relationships between fat mass and bone tissue are complex and not fully elucidated. A high-fat/high-sucrose diet has been shown to induce harmful effects on bone micro architecture and bone biomechanics of rat. When such diet leads to obesity, it may induce an improvement of biomechanical bone parameters in rodent.Here, we examined the impact of a high-fat/high-sucrose diet on the body composition and its resulting effects on bone density and structure in male rats. Forty three Wistar rats aged 7 months were split into 3 groups: 1 sacrificed before diet (BD, n = 14); 1 subjected to 16 weeks of high-fat/high-sucrose diet (HF/HS, n = 14); 1 subjected to standard diet (Control, n = 15). Abdominal circumference and insulin sensitivity were measured and visceral fat mass was weighed. The bone mineral density (BMD) was analyzed at the whole body and tibia by densitometry. Microcomputed tomography and histomorphometric analysis were performed at L2 vertebrae and tibia to study the trabecular and cortical bone structures and the bone cell activities. Osteocalcin and CTX levels were performed to assess the relative balance of the bone formation and resorption. Differences between groups have been tested with an ANOVA with subsequent Scheffe post-hoc test. An ANCOVA with global mass and global fat as covariates was used to determine the potential implication of the resulting mechanical loading on bone.ResultsThe HF/HS group had higher body mass, fat masses and abdominal circumference and developed an impaired glucose tolerance (p < 0.001). Whole body bone mass (p < 0.001) and BMD (p < 0.05) were higher in HF/HS group vs. Control group. The trabecular thickness at vertebrae and the cortical porosity of tibia were improved (p < 0.05) in HF/HS group. Bone formation was predominant in HF/HS group while an unbalance bone favoring bone resorption was observed in the controls. The HF/HS and Control groups had higher total and abdominal fat masses and altered bone parameters vs. BD group.ConclusionsThe HF/HS diet had induced obesity and impaired glucose tolerance. These changes resulted in an improvement of quantitative, qualitative and metabolic bone parameters. The fat mass increase partly explained these observations.

Is protein metabolism changed with obesity

Purpose of reviewAlthough it is well established that obesity is accompanied by various degrees of metabolic impairments especially in the regulation of carbohydrate and lipid metabolism, the influence of obesity on protein metabolism is not clearly understood. The purpose of this review is to present data describing the modification in protein metabolism that have been reported in the clinical setting of obesity. Recent findingsRecent findings suggest that protein metabolism at the whole-body level is less sensitive to insulin action. Impairments in skeletal muscle protein synthesis rates in the postabsorptive state and in response to anabolic factors are reported in obese human. Finally, chronic excessive energy intake and increased adiposity in rats, without the appearance of other metabolic disturbances, do not induce any changes in tissue protein synthesis rates. SummaryBody composition in obesity is characterized by elevated fat mass but also lean body mass which is considered either increased or decreased (in the case of sarcopenic obesity). Thus protein metabolism as reflected by changes in protein synthesis and breakdown might be modified in obese individuals but it is still largely debated. Only a few studies have investigated muscle protein kinetics during obesity and do not lead to the same conclusions prolonging the controversies. Indeed, obesity is associated with many metabolic disturbances which might constitute confounding factors differently affecting muscle protein metabolism.

A well-balanced diet combined or not with exercise induces fat mass loss without any decrease of bone mass despite bone micro-architecture alterations in obese rat

The association of a well-balanced diet with exercise is a key strategy to treat obesity. However, weight loss is linked to an accelerated bone loss. Furthermore, exercise is known to induce beneficial effects on bone. We investigated the impact of a well-balanced isoenergetic reducing diet (WBR) and exercise on bone tissue in obese rats. Sixty male rats had previously been fed with a high fat/high sucrose diet (HF/HS) for 4months to induce obesity. Then, 4 regimens were initiated for 2months: HF/HS diet plus exercise (treadmill: 50min/day, 5days/week), WBR diet plus exercise, HF/HS diet plus inactivity and WBR diet plus inactivity. Body composition and total BMD were assessed using DXA and visceral fat mass was weighed. Tibia densitometry was assessed by Piximus. Bone histomorphometry was performed on the proximal metaphysis of tibia and on L2 vertebrae (L2). Trabecular micro-architectural parameters were measured on tibia and L2 by 3D microtomography. Plasma concentration of osteocalcin and CTX were measured. Both WBR diet and exercise had decreased global weight, global fat and visceral fat mass (p<0.05). The WBR diet alone failed to alter total and tibia bone mass and BMD. However, Tb.Th, bone volume density and degree of anisotropy of tibia were decreased by the WBR diet (p<0.05). Moreover, the WBR diet had involved a significant lower MS/BS and BFR/BS in L2 (p<0.05). Exercise had significantly improved BMD of the tibia possibly by inhibiting the bone resorption, as evidenced by no change in plasma osteocalcin levels, a decrease of CTX levels (p<0.005) and trabecular osteoclast number (p<0.05). In the present study a diet inducing weight and fat mass losses did not affected bone mass and BMD of obese rats despite alterations of their bone micro-architecture. The moderate intensity exercise performed had improved the tibia BMD of obese rats without any trabecular and cortical adaptation.

Nutritional and exercise interventions variably affect estrogen receptor expression in the adipose tissue of male rats

Energy-dense food consumption and lack of physical activity are implicated in the development of the current obesity epidemic. The role of estrogen in adiposity and fuel partitioning is mediated mainly though the estrogen receptor α (ERα) isoform. We hypothesized that nutritional adaptation and exercise training, either individually or combined, could impact ERα expression in adipose tissue relative to glucose tolerance. Seventy-two Wistar rats were submitted to a high-fat, high-sucrose (HF-HS) diet for 16weeks. The first phase of our study was to investigate the effect of an HF-HS diet on whole-body glucose tolerance, as well as on body composition and ERα expression in different adipose tissues. Second, we investigated the effect of switching to a well-balanced diet, with or without exercise training for 8 weeks, on those same parameters. After the first part of this study, HF-HS-fed rats were fatter (8%) than control rats. Despite a decrease in glucose tolerance, ERα expression in adipose tissues was not significantly altered by an HF-HS diet. The return to a well-balanced diet significantly increased ERα expression in perirenal and epididymal adipose tissue, but there was no effect of diet or exercise training on whole-body glucose tolerance. The present findings suggest that diet is a powerful modulator of ERα expression in adipose tissue, as nutritional modulation after an HF-HS diet strongly affects ERα expression, particularly in perirenal and epididymal adipose tissue. However, ERα expression in adipose tissue does not appear to be associated with whole-body glucose tolerance.

Exercise training and return to a well‐balanced diet activate the neuregulin 1/ErbB pathway in skeletal muscle of obese rats

Some studies suggest that neuregulin 1 (NRG1) could be involved in the regulation of skeletal muscle energy metabolism in rodents. Here we assessed whether unbalanced diet is associated with alterations of the NRG1 signalling pathway and whether exercise and diet might restore NRG1 signalling in skeletal muscle of obese rats. We show that diet‐induced obesity does not impair NRG1 signalling in rat skeletal muscle. We also report that endurance training and a well‐balanced diet activate the NRG1 signalling in skeletal muscle of obese rats, possibly via a new mechanism mediated by the protease ADAM17. These results suggest that some beneficial effects of physical activity and diet in obese rats could be partly explained by stimulation of the NRG1 signalling pathway.

A Moderate Supplementation of Native Whey Protein Promotes Better Muscle Training and Recovery Adaptations Than Standard Whey Protein – A 12-Week Electrical Stimulation and Plyometrics Training Study

The purpose of this study was to assess if native whey protein (NW) supplementation could promote recovery and training adaptations after an electrostimulation (ES) training program combined to plyometrics training. Participants were allocated into three groups, supplemented 5 days/week, either with 15 g of carbohydrates + 15 g of NW (n = 17), 15 g of carbohydrates + 15 g of standard whey protein (SW; n = 15), or placebo (PLA; 30 g of carbohydrates; n = 10), while undergoing a 12-week ES training program of the knee extensors. Concentric power (Pmax) was evaluated before, immediately after, as well as 30 min, 60 min, 24 h, and 48 h after the 1st, 4th and last ES training session. The maximal voluntary contraction torque (MVC), twitch amplitude, anatomical cross-sectional area (CSA) and maximal voluntary activation level (VA) were measured before (T0), and after 6 (T1) and 12 weeks of training (T2). Pmax recovery kinetics differed between groups (p < 0.01). Pmax started to recover at 30 min in NW, 24 h in SW and 48 h in PLA. Training adaptations also differed between groups: MVC increased between T0 and T2 in NW (+11.8%, p < 0.001) and SW (+7.1%, p < 0.05), but not PLA. Nevertheless, the adaptation kinetics differed: MVC increased in NW and SW between T0 and T1, but an additional gain was only observed between T1 and T2 in NW. VA declined at T1 and T2 in PLA (−3.9%, p < 0.05), at T2 in SW (−3.5%, p < 0.05), and was unchanged in NW. CSA increased, but did not differ between groups. These results suggest that NW could promote a faster recovery and neuromuscular adaptations after training than SW. However, the mechanisms underlying this effect remain to be identified.