Natalie Chapados

Substituting food restriction by resistance training prevents liver and body fat regain in ovariectomized rats.

Objective Fat mass gain and regain following weight loss are major concerns and may be even more critical after menopause. The present study was undertaken to evaluate the effect of a resistance training protocol on body weight and fat mass in ovariectomized Sprague–Dawley rats following diet-induced weight loss. Design Rats were randomly divided into ovariectomized (Ovx) and sham-operated (Sham) groups. Five weeks after ovariectomy, Ovx rats were subjected to a 26% food restriction (OvxFR) for 8 weeks. Following this period, OvxFR rats went back to a normal ad libitum feeding and were divided into two groups: either sedentary or undergoing a resistance training program for an additional 5 weeks, which consisted of climbing a 6-m vertical grill, 20–40 times, with progressively increasing load four times/week. Results The food restriction program decreased (p < 0.01) body mass, fat pad weight (intra-abdominal and subcutaneous), and liver triacylglycerol (TAG) levels as compared to normally fed Ovx rats. Stopping the food restriction program over a 5-week period resulted in a partial regain in body weight and intra-abdominal fat pad weight (p < 0.05), and in an almost complete regain in liver TAG compared to normally fed Ovx rats. On the other hand, no significant increases in these variables were noted when the food restriction was replaced by resistance training over the same 5-week period. Conclusion These results indicate that a resistance training program could be useful in preventing body weight as well as adipose tissue and liver fat regain in Ovx rats, following diet-induced weight loss. It is suggested that changing from a food restriction regimen to a resistance training program can be an interesting strategy to promote successful long-term weight reduction in postmenopausal women.

Angiomotin p80/p130 ratio: a new indicator of exercise‐induced angiogenic activity in skeletal muscles from obese and non‐obese rats?

Skeletal muscle capillarisation responds to physiological and pathological conditions with a remarkable plasticity. Angiomotin was recently identified as a new pro‐angiogenic molecule. Angiomotin is expressed as two protein isoforms, p80 and p130. Whereas p80 stimulates endothelial cell migration and angiogenesis, p130 is rather characteristic of stabilized and matured vessels. To date, how angiomotin expression is physiologically regulated in vivo remains largely unknown. We thus investigated (1) whether angiomotin was physiologically expressed in skeletal muscle; (2) whether exercise training, known to stimulate muscle angiogenesis, affected angiomotin expression; and (3) whether such regulation was altered in obesity, a pathological situation often associated with an impaired angiogenic activity and some capillary rarefaction in skeletal muscle. Two models of obesity were used: a high fat diet regime and Zucker Diabetic Fatty rats (ZDF). Our results provide evidence that angiomotin was expressed both in capillaries and myofibres. In non‐obese rats, the p80 isoform was increased in plantaris muscle in response to endurance training whereas p130 was unaffected. In obese animals, no change was observed for p80 whereas training significantly decreased p130 expression. Exercise training induced angiogenesis in plantaris from both obese and non‐obese rats, possibly through the modulation of angiomotin level and its consequences on RhoA–ROCK signalling. In conclusion, any increase in p80 or decrease in p130, as respectively observed in non‐obese and obese animals, led to an increased ratio between p80 and p130 isoforms. This increased angiomotin p80/p130 ratio might then directly reflect the enhanced angiogenic ability of skeletal muscle in response to exercise training.

Exercise training increases hepatic endoplasmic reticulum (er) stress protein expression in MTP-inhibited high-fat fed rats.

The purpose of the study was: (1) to determine the effects of microsomal triglyceride transfer protein (MTP) inhibition on endoplasmic reticulum (ER) stress in liver, and (2) to determine if this response is altered in exercise‐trained rats. Female Sprague‐Dawley rats (6 weeks) fed either a standard (SD) or a high‐saturated fat (HF; 43% as energy) diet were trained (Tr) or kept sedentary (Sed) for 6 week. Exercise training consisted of continuous running on a motor‐driven rodent treadmill 5 times/week. Ten days before the end of these interventions, rats were administrated (ip) daily a MTP inhibitor (MTPX) or a placebo (P). MTPX injection resulted in a large (p < 0.01) liver triacylglycerol (TAG) accumulation in SD and HF‐fed rats (∼200 mg g−1), irrespective of the training status, while plasma TAG levels were largely (∼80%) decreased (p < 0.01). MTPX injection in HF but not in SD‐fed animals resulted in an increase in BiP/GRP78, ATF6, PERK, and XBP‐1 mRNA levels, (p < 0.01) indicating an increase in the unfolding protein response (UPR) to ER stress. Interestingly, exercise training in rats fed the HF diet resulted in a further increase in BiP/GRP78 and XBP‐1 mRNA levels in MTPX animals (p < 0.01). It is concluded that: (1) ER stress induced by MTPX occurs only in HF‐fed rats despite the fact that liver TAG levels were largely increased in both dietary models; (2) the increase in gene expression of UPR markers with training may constitute a protective mechanism against ER stress in liver. Copyright

Resistance training attenuates fat mass regain after weight loss in ovariectomized rats

OBJECTIVE The aim of the present study was to investigate the effects of maintaining only one of the two components of a food restriction (FR)+resistance training (RT) regimen on the regain of body weight and fat mass (liver and adipocytes) in ovariectomized (Ovx) rats. METHODS Five week Ovx rats were submitted to a weight loss program consisting of a 26% FR combined with RT (OvxFR+RT) for 8 weeks. RT consisted of climbing a 1.5m vertical grid with a load attached to the tail, 20-40 times with progressively increasing loads 4 times/week. Following this weight loss intervention, OvxFR+RT rats were sub-divided into 3 groups for an additional 5 weeks: 2 groups went back to a normal ad libitum feeding with or without RT and the other group kept only FR. RESULTS Combined FR+RT program in Ovx rats led to lower body mass gain, liver triacylglycerol (TAG) levels, and fat mass gain compared to sedentary normally fed Ovx rats (P<0.01). Stopping both FR and RT over a 5 week period resulted in the regain of body weight, intra-abdominal fat pad weight and liver TAG (P<0.01). When only FR was maintained, the regain of body and fat pad weight as well as liver and plasma TAG concentrations was completely prevented. However, when only RT was maintained, regain in the aforementioned parameters was attenuated but not prevented (P<0.05). CONCLUSION It is concluded that following a FR+RT weight loss program, continuation of only RT constitutes an asset to attenuate body weight and fat mass regain in Ovx rats; although the impact is less than the maintaining FR alone. These results suggest that, in post-menopausal women, RT is a positive strategy to reduce body weight and fat mass relapse.

Exercise training decreases in vitro stimulated lipolysis in a visceral (mesenteric) but not in the retroperitoneal fat depot of high-fat-fed rats

The purpose of the present study was to determine the effects of an exercise training programme in high-fat-fed rats on in vitro lipolysis in a visceral (mesenteric) and a non-visceral fat depot (retroperitoneal) and its relationship to perilipin content. Two groups of female rats were fed a high-fat diet (42 % as energy) for 8 weeks, one remaining sedentary (Sed) and the other being exercise trained (Tr) for this entire period. Rats were killed after 2 and 8 weeks of their respective treatment. The significantly (P < 0.01) higher levels in mesenteric and retroperitoneal fat pad weights, plasma leptin, NEFA and glucose observed with time in Sed high-fat-fed rats were significantly (P < 0.05) attenuated in Tr animals. Isoproterenol-stimulated (10- 5-10- 4 m) lipolysis in the mesenteric, but not in the retroperitoneal tissue, was significantly (P < 0.05) lower (about 57 %) in Tr than in Sed rats after 8 weeks of high-fat feeding. The isoproterenol-stimulated lipolysis in the mesenteric tissue of 8-week Tr high-fat-fed rats was lowered to the level measured in 2-week fat-fed rats although mesenteric fat accumulation was still significantly (P < 0.01) higher in 8- than in 2-week Tr rats. Perilipin content (Western blot) was not affected by the exercise training programme. These results indicate that exercise training resulted in a reduction in the high-fat diet-induced elevated levels of lipolysis in the mesenteric tissue. This response appears to be independent of the perilipin content.

Time course of changes in in vitro lipolysis of intra-abdominal fat depots in relation to high-fat diet-induced hepatic steatosis in rats

The purpose of the present study was to determine the time course of changes in in vitro lipolysis and in perilipin content (Western blot) in the mesenteric and/or the retroperitoneal fat depots in relation to the development of hepatic steatosis in high-fat diet-fed rats. Female Sprague-Dawley rats were submitted to a high-fat diet (HF diet; 42 % as kJ) or a standard diet (SD diet) for 1, 2, 3 or 8 weeks. Fat accretion in the mesenteric and retroperitoneal tissues was higher (P<0.01) in HF diet-fed than in SD diet-fed rats as soon as 1 week after the beginning of the diet. Liver triacylglycerol concentrations were significantly (P<0.01) higher in HF diet-fed than in SD diet-fed rats throughout the experiment, the highest values being reached at week 2 of the diet. Basal and stimulated lipolysis (10(-4) to 10(-7) M-isoproterienol) in the mesenteric and retroperitoneal fat depots was not changed during the first 3 weeks, regardless of the diet. Lipolysis in the mesenteric adipose tissue in the basal and stimulated states was, however, higher (P<0.01) in HF diet-fed than in SD diet-fed rats after 8 weeks of the diets. There were no significant (P>0.05) effects of diet and time on perilipin content of mesenteric tissue. In spite of a rapid fat accretion, the present results do not provide any evidence of a rapid (3 weeks) increase in in vitro lipolysis in intra-abdominal fat depots upon the undertaking of an HF diet at a time where liver lipid infiltration is the most significant.

Liver metabolic disruption induced after a single exposure to PCB126 in rats

Polychlorinated biphenyls (PCBs) have been recognized as metabolic disruptors. The liver plays a pivotal role in detoxification of an organism. Fatty liver results from altered intra-, and extra-hepatic mediators and is associated with increased glucose-related protein 78 (GRP78), commonly used as a marker for endoplasmic reticulum (ER) stress signaling. This pilot study aimed to study the effects of a single exposure on fatty liver metabolic parameters. The objective of the study is to characterize the effects of 3,3′,4,4′,5-pentachlorobiphenyl (PCB126) on ER stress protein chaperon GRP78 and CCAAT-enhancer-binding protein homologous protein (CHOP) and intra-hepatic mediators such as microsomal triglyceride transfer protein (MTP), sterol regulatory element-binding protein 1c (SREBP1c), and peroxisome proliferator-activated receptor alpha (PPARα), as well as extra-hepatic factors such as non-esterified fatty acid (NEFA) and tumor necrosis factor alpha (TNFα). Hepatic GRP78 mRNA and protein levels, indicating the presence of ER stress, were significantly increased following a single PCB126 exposure in rats. Intra-hepatic mechanisms such as lipoprotein secretion pathway (i.e., MTP), lipogenesis de novo (i.e., SREBP1c), and oxidation (i.e., PPARα) were altered in PCB126-treated rats. In addition, a state of inflammation measured by higher TNFα plasma levels was present in contaminated rats. These data indicate that a single injection of PCB126-modulated expression of GRP78 associated with hepatic ER stress and systemic inflammation in rats.

Exercise training increased gene expression of LDL-R and PCSK9 inintestine: link to transintestinal cholesterol excretion

Transintestinal cholesterol excretion (TICE) is known as an alternate non-biliary route of cholesterol excretion from the body. The aim of this study was to determine whether exercise training has effects on intestinal membrane receptors involved in TICE in intact and ovariectomized (Ovx) rats. Sprague-Dawley rats were first divided into 4 groups: Sham operated and Ovx rats fed a standard diet (Sham-SD; Ovx-SD), or a high cholesterol diet (Sham-Chol; Ovx-Chol). These 4 groups were subsequently subdivided into either sedentary or voluntary wheel running groups for 6 weeks. The cholesterol diet resulted in increased hepatic cholesterol accumulation (p< 0.001) in both Sham and Ovx rats. Exercise training increased (p < 0.01) transcripts of intestinal low density lipoprotein receptor (LDL-R) and proprotein convertase subtilisin/kexin type 9 (PCSK9), which are involved in trans-intestinal cholesterol uptake from circulation, in both Sham and Ovx rats compared to rats remaining sedentary in all diet conditions. The up-regulation of intestinal gene expression of LDL-R and PCSK9 following voluntary wheel running in intact and Ovx rats suggests that exercise training may contribute to elimination of cholesterol through the TICE pathway.