Sixteen weeks of resistance training decrease plasma heat shock protein 72 (eHSP72) and increase muscle mass without affecting high sensitivity inflammatory markers' levels in sarcopenic men.

BACKGROUND: Sarcopenia has been associated with increased systemic inflammation and risk of physical disability in older adults. Recently, extracellular heat shock protein 72 (eHSP72) was proposed as a biomarker of sarcopenia but its response to interventions designed to increase muscle mass has never been evaluated. AIMS: The present study was designed to (1) assess eHSP72 levels following resistance training and, (2) determine whether changes in eHSP72 correlate to changes in muscle mass and inflammatory markers. METHODS: A total of 26 sarcopenic men participated in a 16-week resistance training program. The following variables were measured pre-post-intervention: plasma HSP72, serum high sensitivity (hs) inflammatory markers: interleukin-6 (hsIL-6), C-reactive protein (hsCRP), and tumor necrosis factor alpha (hsTNF-α), lean body mass (LBM) and appendicular muscle mass index (appMMI). RESULTS: eHSP72 was detected in 47 % of our participants and its level significantly decreased (P = 0.04) after the intervention, with a concomitant increase in several LBM variables and appMMI (all P < 0.035). Serum hsIL-6, hsCRP and hsTNF-α changes did not reach significance. Baseline hsIL-6 and hsCRP levels were negatively correlated with several LBM variables but solely baseline hsIL-6 was associated with changes in appLBM. No correlations were found between changes in measured variables. DISCUSSION: Attenuation of eHSP72 following resistance training in parallel with increase in LBM variables showed a concordance between the evolution of this biomarker and a clinical outcome relevant to sarcopenia. CONCLUSION: Nevertheless, the low bloodstream detection rate of eHSP72 in a sarcopenic otherwise healthy population might limit its use in clinical settings for now.

Muscle mass and insulin sensitivity in postmenopausal women after 6-month exercise training.

OBJECTIVE: The common belief that high muscle mass improves insulin sensitivity is controversial and even recent studies have established that larger muscle mass is associated with insulin resistance in sedentary postmenopausal women. Physical activity induces a beneficial effect in muscle size and its metabolic properties. Hence, larger muscle mass induced by exercise training should ameliorate insulin sensitivity and the negative relationship between larger muscle mass and insulin sensitivity should disappear. This study examined the induced changes in muscle mass and insulin sensitivity in postmenopausal women after 6-month exercise training along with their possible correlations. METHODS: Forty-eight sedentary, overweight-to-obese postmenopausal women followed a 6-month mixed exercise training (three sessions/week; endurance and resistance). Lean body mass (LBM) and fat mass (FM) were measured by DXA, then the muscle mass index (MMI) was calculated (MMI = LBM (kg)/height (m(2))). Fasting glucose and insulin measurements were obtained and insulin resistance (IR) was estimated by the HOMA-IR formula. RESULTS: Baseline MMI was correlated with IR (r = 0.219, p = 0.015). After intervention, significant differences were observed in body weight, FM%, MMI, and glycemia, and changes in MMI were significantly correlated with changes in IR (r = 0.345, p = 0.016). Also linear regression showed that the increase in MMI explained 28% of the deterioration in insulin sensitivity (p = 0.001). CONCLUSIONS: After 6 months of mixed training, changes in muscle mass remained correlated with changes in insulin resistance, overweight-to-obese women with large muscle gains being more insulin-resistant. This supports that muscle quality and functionality, and the loss of fat mass, should be targeted rather than muscle mass gains in postmenopausal women, especially in a context of no energy restriction.

Variation in C-reactive protein following weight loss in obese insulin resistant postmenopausal women: is there an independent contribution of lean body mass?

BACKGROUND: We showed that obese insulin resistant postmenopausal women are characterized by higher lean body mass and elevated C-reactive protein. Although counterintuitive, we hypothesized that losses in muscle mass following caloric restriction and increase in muscle quality will be associated with improvements in glucose homeostasis through decreases in C-reactive protein. OBJECTIVES: To determine 1) if improvements in C-reactive protein concentrations occurs through losses in lean body mass; and 2) if decreases in C-reactive protein levels contribute to improvements in insulin sensitivity. METHODS: 50 postmenopausal women (body mass index>26 kg/m(²)) with impaired glucose disposal (<7.5 mg/kg/min) completed a 6-month caloric restriction program. Outcome measures were: Glucose disposal rate: M value (by hyperinsulinemic-euglycemic clamp), body composition (total, trunk, and appendicluar). LBM and FM by DXA), LBM index (LBM (kg)/height (m(2)), body fat distribution (VAT and SAT by CT scan) and plasma high-sensitive C-reactive protein (hsCRP) and interleukin-6 (Il-6). RESULTS: Significant correlations were observed between Δ hsCRP levels with Δ Il-6 (r=0.33, p≤0.05), Δ total LBM index (r=0.44, p≤0.01), Δ trunk LBM (r=0.38, p≤0.01) Δ SAT (r=0.35, p≤0.05) and ∆ glucose disposal rate (r=- 0.44, p≤0.01). After including all the correlated variables in Stepwise linear regression model, Δ LBM index was the only independent predictor of the reduction in hsCRP levels (R(2)=0.20, p≤0.01). CONCLUSION: Losses in total lean body mass are independently associated with improvements in inflammatory state (CRP levels) in obese postmenopausal women with impaired glucose disposal.

Effect of exercise training and isoflavones on hepatic steatosis in overweight postmenopausal women.

OBJECTIVES: Postmenopausal women are particularly inclined to an increased risk of developing non-alcoholic hepatic steatosis. The purpose of this study was to investigate whether adding isoflavone supplementation to exercise training could reduce the risk. METHODS: In a 6-month, double-blind, randomized, controlled trial, 54 healthy overweight-to-obese (body mass index 28-40 kg/m2) postmenopausal women were randomly assigned to one of the following groups: (1) exercise and isoflavones (Ex-Iso; n = 26), (2) exercise and placebo (Ex-Pla; n = 28). Exercise training consisted of three weekly sessions of mixed training. We examined the plasma level of specific hepatic enzymes (alanine aminotransferase, aspartate aminotransferase, γ-glutamyltransferase, and alkaline phosphatase) as a reflection of fatty liver along with the calculation of the fatty liver index. All measures were obtained at baseline and after the 6-month intervention. RESULTS: Following the intervention, a lower fatty liver index (p <0.01; 29% in Ex-Iso, 18% in Ex-Pla) and plasma γ-glutamyltransferase (p <0.01; 22% in Ex-Iso, 16% in Ex-Pla) were observed in both groups, with a higher reduction in the Ex-Iso group. On the other hand, for all other hepatic enzymes, there was no change. CONCLUSIONS: Our results show that exercise training appears to bring favorable changes in the plasma level of hepatic enzymes, possibly due to the lowering of liver fat content. While postmenopausal women can benefit from this intervention to decrease the risk of developing non-alcoholic hepatic steatosis, it seems that the addition of isoflavones to exercise training provides some additional effects to those provided by exercise alone.

Liver fat accumulation may be dissociated from adiposity gain in ovariectomized rats.

OBJECTIVE: The purpose of the present study was to establish a model of rats prone and resistant to intra-abdominal fat accumulation in response to ovariectomy (Ovx-P and Ovx-R) and to determine its relationship with molecular biomarkers. DESIGN: Two experiments were conducted in which female rats were either sham-operated (Sham) or ovariectomized (Ovx). In the first experiment, ovariectomized rats were stratified into three tertiles based on intra-abdominal adipose tissue mass. To strengthen the Ovx-P/Ovx-R model, we conducted a second experiment in which the numbers of rats in each group were extended and in which different molecular markers were measured. At the end of a 6-8-week period, ovariectomized rats that displayed the lower abdominal fat accumulation (lower tertile) were labelled as Ovx-R and those in the upper tertile as Ovx-P. RESULTS: Ovx-R rats displayed similar abdominal fat gain to Sham rats whereas Ovx-P rats depicted abdominal fat mass twice as high as that of Sham and Ovx-R rats. Despite the difference in abdominal adiposity, liver fat content was ~50% higher (p < 0.01) in both Ovx-R and Ovx-P rats compared to Sham rats. In addition, both Ovx-R and Ovx-P rats depicted higher HOMA-IR scores (p < 0.05) and lower (p < 0.01) hepatic gene expression of leptin receptor-b and -e, microsomal transfer protein (MTP), and diacylglycerol acyltransferase-2 (DGAT-2) compared to Sham rats. CONCLUSION: The present findings indicate that estrogen withdrawal-induced hepatic steatosis and associated insulin resistance may be dissociated from abdominal fat accumulation and suggest that a decrease in leptin action through a down-regulation of leptin receptors and a decrease in very low density lipoprotein production through a down-regulation of MTP and DGAT-2 may be factors responsible for this observation in the absence of peripheral fat gain.

Hepatic VLDL-TG production and MTP gene expression are decreased in ovariectomized rats: effects of exercise training.

The present study was designed to investigate the effects of estrogen withdrawal and exercise training on hepatic very low density lipoprotein-triglyceride (VLDL-TG) production and on expression of genes involved in hepatic VLDL synthesis in response to lipid infusion. Female Sprague-Dawley rats underwent ovariectomy (Ovx), sham surgery (Sham), and Ovx with 17ß-estradiol supplementation (OvxE2) before being subdivided into sedentary (Sed) and trained (Tr) groups for 8 weeks. Exercise training consisted of continuous running on a rodent treadmill 5 times/wk. At the end of the 8-week period, all rats in the fasted state were intravenously infused with a 20% solution of Intralipid for 3-h followed by an injection of Triton WR-1339 to block lipoprotein lipase activity. Plasma TG accumulation was subsequently measured during 90 min to estimate VLDL-TG production. An additional control group consisting of Sham-Sed rats was infused with saline (0.9% NaCl). Estrogen withdrawal resulted in higher (p<0.01) liver fat accumulation concomitantly with lower (p<0.01) VLDL-TG production and lower mRNA and protein content of hepatic microsomal triglyceride transfer protein (MTP). All of these effects in Ovx rats were corrected with estrogen supplementation. Training in Ovx rats reduced (p<0.01) liver fat accumulation and further reduced (p<0.01) hepatic VLDL-TG production along with gene expression of MTP and diacylglycerol acyltransferase-2 (DGAT-2). It is concluded that VLDL-TG synthesis and/or secretion is decreased in Ovx rats probably via MTP regulation and that this decrease may constitute one of the factors involved in hepatic fat accumulation. The training effect on reducing VLDL production was independent of the estrogenic status.

Does exercise training prior to ovariectomy protect against liver and adipocyte fat accumulation in rats?

OBJECTIVE: To determine whether a training state protects against the metabolically deleterious effects of ovariectomy on liver and adipocyte fat accumulation in rats. DESIGN: Female rats were randomly assigned to each group (n = 8 rats/group). The animals were first either exercise-trained (Tr) for 6 weeks or kept sedentary (Sed) before being sham-operated (Sham), ovariectomized (Ovx), or ovariectomized with 17beta-estradiol supplementation (OvxE2). Following surgery, sedentary rats either remained sedentary (Sed-Sed) or undertook exercise training for 6 weeks (Sed-Tr) while exercise-trained rats either became sedentary (Tr-Sed) or resumed exercise training (Tr-Tr). RESULTS: Body weight and energy intake along with intra-abdominal and subcutaneous fat pad weights and homeostasis model assessment of insulin resistance (HOMA-IR) were significantly (p < 0.01) increased in the Ovx group compared to the Sham and OvxE2 groups. Rats kept in a sedentary state after surgery showed the higher (p < 0.05) values for all of these variables whether they were trained or not before surgery (Sed-Sed and Tr-Sed), indicating no protective effect of a previous exercise-trained state. On the other hand, training conducted after surgery resulted in a lowering of fat mass and HOMA-IR whether rats had been trained or not before surgery (Sed-Tr and Tr-Tr), indicating the effectiveness of exercise training even initiated after surgery. These responses were independent of surgery. Interestingly, liver triacylglycerol concentrations followed a pattern of responses identical to fat mass with the exception that all of the responses were observed only in the Ovx group (p < 0.05). CONCLUSION: There is no protective effect of a previous exercise-training state on ovariectomy-induced liver and adipocyte fat accumulation if rats remain sedentary after ovariectomy. However, training conducted concurrently with estrogen withdrawal has protective effects, especially on liver fat accumulation, whether or not rats were previously trained.

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.