Maude Gerbaix

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.

Visceral fat mass determination in rodent: validation of dual-energy x-ray absorptiometry and anthropometric techniques in fat and lean rats

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.

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.

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.