Two weeks of western diet disrupts liver molecular markers of cholesterol metabolism in rats.

BACKGROUND: The present study was designed to test the hypothesis that in the liver, excessive fat accumulation impairs cholesterol metabolism mainly by altering the low-density lipoprotein-receptor (LDL-R) pathway. METHOD: Young male Wistar rats were fed standard (SD), high fat (HFD; 60% kcal) or Western (WD; 40% fat + 35% sucrose (17.5% fructose)) diets for 2 or 6 weeks. RESULTS: Weight gain (~ 40 g) was observed only following 6 weeks of the obesogenic diets (P < 0.01). Compared to the 2-week treatment, obesogenic diets tripled fat pad weight (~ 20 vs 7 g) after 6 weeks. Hepatic triglyceride (TG) levels were greater in response to both the WD and HFD compared to the SD (P < 0.01) at 2 and 6 weeks and their concentrations were greater (P < 0.05) in WD than HFD at 2 weeks. Plasma total cholesterol levels were higher (P < 0.05) in animals submitted to WD. After 2 and 6 weeks, liver expression of LDL-R, proprotein convertase subtilisin/kexin 9 (PCSKk9) and sterol regulatory element binding protein 2 (SREBP2), involved in LDL-cholesterol uptake, was lower in animals submitted to WD than in others treated with HFD or SD (P < 0.01). Similarly, low-density lipoprotein-receptor-related protein 1 (LRP1) and acyl-CoA cholesterol acyltransferase-2 (ACAT-2) mRNA levels were lower (P < 0.01) among WD compared to SD-fed rats. Expression of the gene coding the main regulator of endogenous cholesterol synthesis, 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCoAR) was reduced in response to WD compared to SD and HFD at 2 (P < 0.001) and 6 (P < 0.05) weeks. Being enriched in fructose, the WD strongly promoted the expression of carbohydrate-response element binding protein (ChREBP) and acetyl-CoA carboxylase (ACC), two key regulators of de novo lipogenesis. CONCLUSION: These results show that the WD promptly increased TG levels in the liver by potentiating fat storage. This impaired the pathway of hepatic cholesterol uptake via the LDL-R axis, promoting a rapid increase in plasma total cholesterol levels. These results indicate that liver fat content is a factor involved in the regulation of plasma cholesterol.

Exercise training increased gene expression of LDL-R and PCSK9 in intestine: 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.

Energy Density is Not a Consistent Correlate of Adiposity in Women During the Menopausal Transition.

PURPOSE: The association between the energy density (ED) of foods and adiposity has been reported previously. However, whether the contribution of ED to adiposity remains significant when controlled for energy intake (EI) and physical activity energy expenditure (PAEE) remains to be clearly established. We aimed to investigate the independent contribution of ED to variations in body composition in women during the menopausal transition. METHODS: Sixty-seven women from the MONET cohort study were analyzed. Seven-day food records were used to assess EI and ED. Body composition (body fat mass (FM) and trunk-fat mass (TFM)) was measured with dual-energy X-ray absorptiometry; PAEE was assessed with accelerometers. This secondary analysis of data included measurements obtained at years 1 and 5 of the study. RESULTS: Mean ED was correlated with FM (r = 0.22; P = 0.04) and TFM (r = 0.22; P = 0.04) at year 1, but not at year 5. The multiple regression analysis showed that EI and ED contributed to 14% of the variance in FM and TFM at year 1. CONCLUSION: These results suggest that ED is a modest but inconsistent determinant of adiposity in healthy women at the time of the menopause transition.

Effect of a high-fat diet on the hepatic expression of nuclear receptors and their target genes: relevance to drug disposition.

More than 1·4 billion individuals are overweight or obese worldwide. While complications often require therapeutic intervention, data regarding the impact of obesity on drug disposition are scarce. As the influence of diet-induced obesity on drug transport and metabolic pathways is currently unclear, the objective of the present study was to investigate the effect of high fat feeding for 13 weeks in female Sprague-Dawley rats on the hepatic expression of the nuclear receptors pregnane X receptor (PXR), constitutive androstane receptor (CAR), liver X receptor (LXR) and farnesoid X receptor (FXR) and several of their target genes. We hypothesised that high fat feeding would alter the gene expression of major hepatic transporters through a dysregulation of the expression of the nuclear receptors. The results demonstrated that, along with a significant increase in body fat and weight, a high-fat diet (HFD) induced a significant 2-fold increase in the expression of PXR as well as a 2-, 5- and 2·5-fold increase in the hepatic expression of the PXR target genes Abcc2, Abcb1a and Cyp3a2, respectively (P< 0·05). The expression levels of FXR were significantly increased in rats fed a HFD in addition to the increase in the expression levels of FXR target genes Abcb11 and Abcb4. The expression levels of both LXRα and LXRß were slightly but significantly increased in rats fed a HFD, and the expression levels of their target genes Abca1 and Abcg5, but not Abcg8, were significantly increased. The expression of the nuclear receptor CAR was not significantly altered between the groups. This suggests that a HFD may induce changes in the hepatobiliary transport and metabolism of endogenous and exogenous compounds.

High dietary cholesterol and ovariectomy in rats repress gene expression of key markers of VLDL and bile acid metabolism in liver.

BACKGROUND: The purpose of the study was to evaluate the effects of high dietary cholesterol in ovariectomized (Ovx) rats on several key markers of hepatic cholesterol and bile acid metabolism. METHOD: Ovx and sham operated (Sham) rats were given either a standard diet (SD), a SD diet supplemented with 0.25% cholesterol (SD + Chol), or a high fat diet supplemented with 0.25% cholesterol (HF + Chol) for 5 weeks. RESULTS: Ovx was associated with higher (P < 0.05) liver total cholesterol (TC) under the SD and the SD + Chol diet, while liver triglyceride (TG) content was higher in Ovx than in Sham rats in all 3 diet conditions. Surprisingly, the SD + Chol diet was associated with lower (P < 0.001) plasma TC and TG levels in Ovx than in Sham rats, suggesting a decrease in VLDL secretion. Accordingly, several transcripts of key markers of VLDL synthesis including microsomal TG transfer protein (Mttp) and Apob-100 were decreased (P < 0.05) in Ovx compared to Sham rats under the three dietary conditions and even more so for Mttp and Apob-100 when rats were fed the SD + Chol diet. Transcripts of bile acid transporters including bile salt export pump (Bsep) and Na + -taurocholate cotransporting polypeptide (Ntcp) were decreased by the addition of cholesterol to the SD diet in both Ovx and Sham rats. CONCLUSION: These results indicate that a high cholesterol feeding and ovariectomy combine to reduce the gene expression of key markers of VLDL synthesis suggesting a reduction in excretion of cholesterol from the liver.

Impaired VLDL assembly: a novel mechanism contributing to hepatic lipid accumulation following ovariectomy and high-fat/high-cholesterol diets?

The aim of the present study was to identify molecular mechanisms involved in liver fat and cholesterol accumulation in ovariectomised (Ovx) rats fed with high-cholesterol diets. VLDL assembly and bile acid metabolism were specifically targeted. After being either Ovx or sham-operated, the rats were fed a standard diet or a high-fat diet containing 0, 0·25 or 0·5 % cholesterol for 6 weeks. Although Ovx rats exposed to dietary cholesterol intake accumulated the greatest amount of hepatic fat and cholesterol, plasma cholesterol levels were lower (P< 0·05) in these animals than in the corresponding control rats. Accompanying this observation, ovariectomy and dietary cholesterol intake resulted in a down-regulation (P< 0·05) of the expression of genes associated with VLDL assembly, including microsomal TAG transfer protein, diacylglycerol acyltransferase 2, acyl-CoA:cholesterol acyltransferase 2 and apoB-100 as well as genes associated with bile acid metabolism including farnesoid X receptor and bile salt export pump (P< 0·01). These results indicate that high-fat/high-cholesterol diets and ovariectomy concomitantly disrupt hepatic lipid output through defects in VLDL assembly and, most probably, secretion. The results also point to a defect in hepatic bile acid secretion. The present study offers novel insights into intrahepatic lipid metabolism, which may be relevant to metabolic complications found in postmenopausal women.

Synergistic associations of physical activity and diet quality on cardiometabolic risk factors in overweight and obese postmenopausal women.

Healthy diet and physical activity are associated with a lower cardiometabolic risk (CMR). Little is known about whether they interact to improve CMR. The purpose of the present study was to determine the synergistic associations of diet quality and physical activity energy expenditure (PAEE) on CMR factors. The present study was an a posteriori analysis of two cross-sectional studies on 124 inactive non-diabetic postmenopausal women with a BMI ≥ 27 kg/m². The following factors were measured: diet quality (assessed by the Canadian Healthy Eating Index (C-HEI) from a 3 d food record); PAEE (doubly labelled water); body composition (dual-energy X-ray absorptiometry, computed tomography scan); lipoprotein profile (total, HDL- and LDL-cholesterol (HDL-C and LDL-C), non-HDL-C, total cholesterol:HDL-C, TAG, apoA1, apoB, apoA1:apoB and LDL-C:apoB); insulin sensitivity (homeostasis model assessment of insulin resistance and hyperinsulinaemic-euglycaemic clamp); inflammatory markers (high-sensitivity C-reactive protein (hs-CRP), haptoglobin, orosomucoid, IL-6 and leucocyte count). The association of the interaction PAEE × C-HEI and CMR factors was evaluated by hierarchical regressions. Fat mass-adjusted ANCOVA determined the interaction between PAEE and the C-HEI. In hierarchical regressions, the interaction PAEE × C-HEI was a correlate of more favourable values of HDL-C, apoB, apoA1:apoB and LDL-C:apoB ratios, and hs-CRP, while only PAEE was a negative correlate of haptoglobin. Compared with those in the low-PAEE/low-C-HEI group, women in the high-PAEE/high-C-HEI group had 10 % higher HDL-C, 13 % lower apoB, 11 % larger LDL particles and 28 % lower hs-CRP concentrations (P< 0·05). PAEE and the C-HEI have a synergistic association with the CMR profile. These results support the integration of both diet quality and physical activity in the management of CMR.

An atherogenic diet decreases liver FXR gene expression and causes severe hepatic steatosis and hepatic cholesterol accumulation: effect of endurance training.

PURPOSE: The aim of this study was to determine the effects of an atherogenic diet (AD; 40 % lipid, 1.25 % cholesterol, kcal) on triglyceride (TAG) and cholesterol accumulation in liver and on gene expression of liver X receptor (LXR) and farnesoid X receptor (FXR) and their target genes and to observe if these responses are affected by endurance training. METHODS: Sprague-Dawley rats (n = 32) were divided into two groups and randomly assigned to an AD or a standard diet (SD) for 7 weeks. Half of the rats in each group were assigned to an exercise training program for 5 days/week. RESULTS: The AD resulted in a large (P < 0.01) accumulation in liver TAG (4×) along with elevated liver and plasma cholesterol without any gain in peripheral fat mass. The liver TAG and cholesterol accumulations were associated with an important reduction (P < 0.01; 60 %) in FXR, but no change in LXR transcripts. Accompanying the reduction in FXR gene expression, we found an increase (P < 0.001) in SREBP-1c and a decrease (P < 0.01) in MTP mRNAs suggesting an increased lipogenesis and a reduced VLDL production, respectively. The AD was also associated with lower HMG-CoA-r, squalene synthase, and ABCG8 transcripts (P < 0.001). In the intestine, exercise training resulted in higher NPC1L1, ABCG5, and ABCG8 in SD-fed animals, while all these increases were suppressed under the AD feeding. CONCLUSIONS: It is concluded that dietary cholesterol favors liver TAG and cholesterol accumulations associated with an important reduction in FXR transcripts.

Exercise training decreases hepatic SCD-1 gene expression and protein content in rats.

Stearoyl-CoA desaturase-1 (SCD-1) is the rate limiting enzyme in the biosynthesis of saturated-derived monounsaturated fats that are the major constituents of very-low-density-lipoproteins-triacylglycerol (VLDL-TAG) and are involved in regulating cellular metabolism. The purpose of this study was to evaluate the effects of an 8-week exercise training program on the hepatic gene expression of this crucial enzyme. Female rats either trained (TR) or kept sedentary (Sed) for 8 weeks were submitted either to standard (SD) diet for 8 or for 6 weeks followed by high-fat (HF; 42% kcal) diet for 2 weeks. The 2-week-high fat feeding resulted in an increase in liver triacylgycerol (TAG), plasma free-fatty-acids (FFA), abdominal fat mass, sterol-regulatory-element-binding protein-1c (SREBP-1c), and carbohydrate-response-element-binding protein (ChREBP) gene expression in liver along with a decrease in SCD-1 gene expression and plasma and liver SCD-1 desaturation index (C16:1/C16:0). Liver TAG, plasma FFA, SREBP-1c mRNA, and SCD-1 desaturation indexes (C16:1/C16:0; C18:1/C18:0) were not changed in liver or in plasma by the training program. Nevertheless, training resulted in an important decrease in fat mass (P < 0.01), hepatic SCD-1 mRNA levels (P < 0.01), and protein content (P < 0.05) in both SD and HF fed rats. It is concluded that despite an absence of decreased liver TAG, exercise training contributes to the proper regulation of fat metabolism by down-regulating hepatic SCD-1 gene expression and protein content.

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 (approximately 200 mg g(-1)), irrespective of the training status, while plasma TAG levels were largely (approximately 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.

Effects of the addition of a resistance training programme to a caloric restriction weight loss intervention on psychosocial factors in overweight and obese post-menopausal women: a Montreal Ottawa New Emerging Team study.

The aim of this study was to examine the effects of the addition of a resistance training programme to a caloric restriction weight loss intervention on psychosocial profile. The study sample consisted of 137 overweight and obese post-menopausal women. Participants were randomized to a caloric restriction group and caloric restriction + resistance training group. Psychosocial, anthropometric, and metabolic variables were measured before and after the 6-month weight loss intervention. Both groups presented similar weight loss and there were no significant differences between the caloric restriction group and caloric restriction + resistance training group for changes in psychosocial profile. Thereafter, all participants were classified into quintiles based on the amount of weight loss. In all quintiles, women markedly improved body esteem and self-esteem, and decreased hunger and perceived risk for diabetes mellitus (P < 0.05). However, significant increases in dietary restraint were observed in quintiles 2-5 (> or =2.4 % body weight loss), decreases in disinhibition in quintiles 3-5 (> or =4.9 %), increases in self-efficacy in quintiles 3-5 (> or =4.9 %), and increases in health perceptions in quintile 5 (> or =11.1%). The results of this study do not support the hypothesis that the addition of a resistance training programme to a caloric restriction weight loss intervention has additional benefits on psychosocial profile. Overall, the significant improvements in the psychosocial profile observed were mostly accounted for by the degree of weight loss.

Downregulation of oxytocin and natriuretic peptides in diabetes: possible implications in cardiomyopathy.

Regular physical activity is beneficial in preventing the risk of cardiovascular complications of diabetes. Recent studies showed a cardioprotective role of oxytocin (OT) to induce natriuretic peptides (NPs) and nitric oxide (NO) release. It is not known if the diabetic state is associated with a reduced OT-NPs-NO system and if exercise training improves this system. To address this, we investigated the effects of treadmill running using the db/db mouse model of type 2 diabetes. Eight-week-old db/db mice were subjected to running 5 days per week for a period of 8 weeks. The lean db/+ littermates were used as controls. Sedentary db/db mice were obese and hyperglycaemic, and exercise training was not effective in reducing body weight and the hyperglycaemic state. Compared to control mice, db/db mice had lower heart weight and heart-to-body weight ratios. In these mice, this was associated with augmented cardiac apoptosis, cardiomyocyte enlargement and collagen deposits. In addition, db/db mice displayed significant downregulation in gene expression of OT (76%), OT receptors (65%), atrial NP (ANP; 43%), brain NP (BNP; 87%) and endothelial nitric oxide synthase (eNOS) (54%) in the heart (P < 0.05). Exercise training had no effect on expression of these genes which were stimulated in control mice. In response to exercise training, the significant increment of anti-apoptotic Bcl-2 gene expression was observed only in control mice (P < 0.05). In conclusion, downregulation of the OT-NPs-NO system occurs in the heart of the young db/db mouse. Exercise training was not effective in reversing the defect, suggesting impairment of this cardiac protective system in diabetes.

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.

Change in plasma acylation stimulating protein during euglycaemic-hyperinsulinaemic clamp in overweight and obese postmenopausal women: a MONET study.

OBJECTIVE: Acylation-stimulating protein (ASP) has been shown to positively stimulate fatty acid esterification and glucose uptake in adipocytes. In vitro studies demonstrate that insulin stimulates ASP secretion from adipocytes. Individuals with obesity and/or metabolic disturbances (insulin resistance and type 2 diabetes) have increased plasma ASP. DESIGN: The present study was designed to evaluate whether ASP levels are influenced by the metabolic profiles of overweight and obese postmenopausal women during a euglycaemic/hyperinsulinaemic clamp (EHC). Patients The study population consisted of 76 overweight and obese sedentary postmenopausal women. MEASUREMENTS: We evaluated insulin sensitivity, plasma ASP levels, body composition including visceral adipose tissue area, blood lipid profiles, liver enzymes, peak aerobic capacity, resting metabolic rate (RMR) and total energy expenditure (TEE). RESULTS: We observed wide interindividual variations of ASP levels during the EHC. Therefore, subjects were divided into three groups based on ASP changes. Negative ASP Responders (NAR; n = 24) showed a -20% or greater decrease in ASP levels while Positive ASP Responders (PAR; n = 42) displayed ASP fluctuations superior to +20%. Ten subjects had little or no ASP change and were considered as Zero ASP responders (ZAR). PAR women displayed a worse metabolic profile than NAR women, including higher BMI, visceral adipose tissue, fasting insulin levels, lean body mass, and alanine aminotransferase (ALT), a marker of impaired liver function. After adjustment for BMI, only ALT remained significantly different, while lean body mass (P = 0.08) and visceral adipose tissue (P = 0.07) remained marginally higher. Correlation analysis of all subjects demonstrated that fasting ASP levels correlated positively with albumin and VO(2 peak) and this association remained significant after adjustments for the effect of BMI. In addition, the percentage maximal change in ASP levels during the EHC was positively associated with BMI, lean body mass, visceral adipose tissue, fasting insulin, HOMA, TEE, RMR, ALT and AST. CONCLUSION: Overall these results suggest that an elevated ASP response during the EHC is associated with metabolic disturbances in overweight and obese postmenopausal women.

Exercise training decreases plasma leptin levels and the expression of hepatic leptin receptor-a, -b, and, -e in rats.

In addition to acting in the central nervous system, leptin also acts on peripheral tissues such as liver to provide a protection against lipid accretion. Previous evidence from human and animal model indicates that exercise training reduces circulating leptin levels beyond the changes in adiposity levels. Because liver is one of the main peripheral organs for leptin action, this present study was designed to determine whether leptin receptors expression in liver is changed by exercise training. Female rats trained (TR) or kept sedentary (Sed) for 8 weeks were submitted either to a standard (SD) diet for 8 weeks or for 6 weeks followed by 2 weeks of high-fat (HF) or high-carbohydrate (HC) feeding. Food intake, adiposity levels, circulating plasma leptin and insulin concentrations along with the hepatic expression of leptin receptors (ObR-a, -b, and -e) and peroxisome proliferator-activated receptor alpha (PPARalpha) and peroxisome proliferator-activated receptor-gamma co-activator-1alpha (PGC-1alpha), were measured in all the animals. Intra-abdominal fat depots were increased under the HF but not under the HC diet. As expected, exercise training decreases intra-abdominal adiposity in animals fed with the SD and the HF diet, and to a lesser extent in HC-fed rats. Plasma leptin levels either expressed in absolute values or in values relative to adiposity levels were significantly (P < 0.05) increased with the HF diet and significantly decreased in TR animals, independently of the diet. Moreover, a significant (P < 0.01) reduction in hepatic gene expression of ObR-a, -b and -e was found in TR animals in all the three diet conditions. PPARalpha and PGC-1alpha mRNAs were also decreased (P < 0.05) in TR animals in two out of three diet conditions. The present findings indicate that exercise training-induced decrease in plasma leptin levels is accompanied by a reduction in gene expression of three different isoforms of leptin receptors in liver.

Variability of strength measurement in postmenopausal women who are overweight or obese: a Monet study.

The main objective of this study was to establish whether a stable measurement of strength could be obtained without prior exercise familiarization in postmenopausal women who were overweight or obese. A second objective was to evaluate the influence of physical activity on the variability of strength measurement. Thirty postmenopausal women (age: 57.9 yr; SD: 5 yr; body mass index: 31.0 kg/m2; SD: 4 kg/m2) underwent 3 strength testing sessions (48 hr apart) each including 3 exercises (leg press, chest press, and lat pull down). Energy expenditure was measured before the strength testing week with the doubly labelled water method over a 10-day period. Resting metabolic rate was measured by indirect calorimetry. Physical activity energy expenditure was calculated as follows: total energy expenditure x 0.9, minus the resting metabolic rate. Repeated analysis of variance and paired t-test were used to assess the difference and the reliability of the testing sequence. Results from leg press and chest press exercises indicated no significant difference among the 3 testing sessions. The lat pull down exercise was associated with a significant systematic bias between sessions 1 and 2 (mean difference: 1.4 kg; SD: 3 kg; 95% confidence intervals; 0.2-2.7 kg), but the difference disappeared at the third testing session (mean difference: 0.7 kg; SD: 3 kg; 95% confidence intervals; 0.5-2 kg). Physical activity did not influence the variability of the strength results. Overall, our results showed that a relatively stable strength measurement can be obtained within a maximum of 3 testing sessions without prior familiarization. In addition, physical activity did not influence strength testing in postmenopausal women who were overweight or obese.

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.

Liver of ovariectomized rats is resistant to resorption of lipids.

Ovarian hormones have been shown to regulate liver lipid accumulation in rats. The present study was designed to evaluate liver lipid resorption in ovariectomized (Ovx) rats. Ovx and sham-operated (Sham) rats were submitted to a high-fat (HF; 43% kcal fat as energy) diet for 5 weeks and then either maintained on this diet or switched to a standard (SD; 12.5% kcal fat as energy) diet till weeks 8 and 13 (n=8 rats/group). Body weight, energy intake, liver and intra-abdominal fat accumulation and plasma metabolic profile were determined. Body weight was significantly (P<0.01) higher in Ovx than in Sham groups at all times and switching diet did not alter the body weight pattern. The weight of the intra-abdominal fat depots and plasma leptin levels, along with liver triacylglycerol (TAG) concentrations, were significantly higher (P<0.01) in Ovx than in Sham rats. Switching diet reduced intra-abdominal fat depot weight and plasma leptin in all groups. Switching diet also resulted in a decrease in liver fat accumulation in Sham rats at all times. However, 8 weeks after the diet switch (week 13) liver fat accumulation was as high in Ovx rats as those maintained on the HF diet. When liver TAG values measured at week 13 were compared to initial pre-switching values (week 5), liver TAG levels in Ovx animals were maintained at the same level independently of the diet switch, while in Sham rats switching to a SD diet reduced liver TAG accumulation (P<0.05). The same comparisons with plasma TAG levels revealed an opposite relationship. These data suggest that liver lipid resorption in Ovx animals is more related to the ovarian hormone status than to the type of ingested diet.

Resistance training prevents liver fat accumulation in ovariectomized rats.

BACKGROUND: Menopause is associated with increased lipid deposition in the liver and fat accumulation in the abdomen. OBJECTIVE: The purpose of the present study was to determine the effects of adding a resistance training program (RT) to a restrictive diet (RD) on liver lipid accumulation and abdominal fat depots in ovariectomized (Ovx) rats. METHODS: One group of sham-operated and three groups of Ovx rats were compared. Five weeks after surgery, Ovx rats were either submitted to an approximately 25% RD with or without RT for 3 or 8 weeks, while a third group of Ovx rats were fed ad libitum and remained sedentary. The RT program consisted of climbing a 6m vertical metal grill five times a week with an increasing load up to 75% of body weight attached to the tail. The number of repetitions increased from two to four sets of 10 repetitions. RESULTS: Ovariectomy resulted in significantly higher (P<0.01) body weight, energy intake, intra-abdominal fat depots, plasma leptin levels (P<0.05), and liver triacylglycerol concentrations. All of these responses were (P<0.01) reduced in Ovx rats following the RD with the exception of liver lipid infiltration. The addition of RT to the RD treatment synergistically reduced abdominal fat deposition and plasma-free fatty acid levels. Moreover, liver lipid infiltration was completely prevented by the addition of the RT program. Muscle mass relative to body weight was significantly increased in Ovx-RD-RT compared to all other groups. CONCLUSION: It is concluded that RT is an asset to minimize the deleterious effects of ovarian hormone withdrawal on liver lipid accumulation and abdominal fat accumulation in Ovx rats.

Body composition, cardiometabolic risk factors, physical activity, and inflammatory markers in premenopausal women after a 10-year follow-up: a MONET study.

OBJECTIVE: Menopausal transition and postmenopause are usually associated with changes in body composition and a decrease in physical activity energy expenditure (PAEE). This study investigated body composition, cardiometabolic risk factors, PAEE, and inflammatory markers in premenopausal women after a 10-year follow-up. METHODS: In all, 102 premenopausal women participated in the 5-year observational longitudinal Montreal Ottawa New Emerging Team (MONET) study. This present substudy included 48 participants (age: 60.0 ±â€Š1.7 years; body mass index: 23.2 ±â€Š2.2 kg/m) 6.0 ±â€Š0.3 years after completion of the initial MONET study. Measures included body composition, waist circumference (WC), fasting glucose and insulin levels, insulin sensitivity (QUICKI model), plasma lipid levels, PAEE, and inflammatory markers. RESULTS: Compared with baseline measures of the MONET study, analyses revealed no significant increase in body weight, although there were significant increases in WC, fat mass (FM), % FM, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol, haptoglobin, apolipoprotein B, ferritin, adiponectin, and soluble cluster of differentiation 14 (all P < 0.001) after the 10-year follow-up. However, significant decreases were observed for fat-free mass, PAEE, fasting glucose levels, interleukin-8 levels, and soluble tumor necrosis factor receptors 1 and 2 (sTNFR-1 and sTNFR-2) levels (all P < 0.05). To determine the effect of postmenopausal years, data were restructured based on final menstrual period (FMP), and one-way analyses of variance were performed.Waist circumference, % FM, total cholesterol, high-density lipoprotein cholesterol, apolipoprotein B, ferritin, adiponectin, and soluble cluster of differentiation 14 were higher in early and late postmenopausal periods in these women. sTNFR-1 and sTNFR-2 levels were higher at the FMP and early postmenopausal years as compared with the late postmenopausal periods. Finally, interleukin-8 levels were lower in years after FMP. CONCLUSION: The number of years elapsed since the FMP can affect body composition, cardiometabolic risk factors, and inflammatory markers in healthy premenopausal women going through menopausal transition and postmenopausal periods.