Modalities of exercise training on liver fat accretion and inflammatory markers in ovariectomized rats

Les facteurs de risque des maladies cardiovasculaires, telle, que la détérioration du profil lipidique, deviennent plus prononcés après la ménopause, ce qui fait de la maladie coronarienne, l’une des principales causes de décès chez les femmes ménopausées. Une proportion importante de femmes prennent du poids après la ménopause en particulier dans la région abdominale entraînant par conséquent des perturbations métaboliques. Des données récentes suggèrent également que l’absence des œstrogènes observée à la ménopause favorise le développement de la stéatose hépatique. Cette dernière a été incriminée pour incriminée dans le développement de la résistance à l'insuline, et est de ce fait considérée comme une composante hépatique du syndrome métabolique. Il est impératif d'établir des stratégies visant à contrecarrer l'accumulation de graisse dans le foie et l’accroissement du tissu adipeux chez les femmes ménopausées, en tenant compte que l'utilisation de l'hormonothérapie substitutive est de nos jours moins soutenue. Les quatre études de la présente thèse ont été conduites pour tenter de fournir des informations sur le traitement et la prévention de l’augmentation de la masse graisseuse et de la stéatose hépatique qu’entraîne la suppression des œstrogènes, à travers les modifications du mode de vie (diète et exercice physique) chez la rate ovariectomizée (Ovx); un modèle animal de la ménopause. Dans les deux premières études nous nous sommes concentrés sur l’augmentation de la masse graisseuse et sa reprise suite à une perte de poids. Dans la première étude, nous avons montré que les rates Ovx qui ont suivi un programme de restriction alimentaire (FR) ont diminué significativement (P < 0.01) leur poids corporel, leur contenu en graisses intra-abdominales ainsi que leurs triacylglycérols (TAG) hépatiques, comparativement aux rates Ovx nourries à la diète normale. De plus, l’entraînement en résistance (RT) a prévenu la reprise de poids corporel ainsi que l’accroissement du tissu adipeux et l’accumulation de lipides dans le foie des rates Ovx, après l’arrêt du régime amaigrissant. Les résultats de la deuxième étude ont confirmé l'efficacité de la restriction alimentaire associée à l’entraînement en résistance (FR + RT) dans la réduction du poids corporel, des lipides dans le foie et le tissu adipeux chez les rates Ovx. Tenant compte des résultats de notre première étude, l’entraînement en résistance seulement a constitué un atout pour atténuer le poids corporel et la masse grasse reprise par les rates Ovx suite à un programme de perte de poids (FR + RT); bien que l'impact ait été moindre comparé au maintien seul de la restriction alimentaire. De la même manière que la supplémentation en œstrogènes, les résultats de la troisième étude indiquent que l'entraînement en endurance mené concurremment avec l’ovariectomie a significativement atténué l'accumulation de lipides dans le foie ainsi que dans le tissu adipeux. Toutefois, l’entraînement en endurance effectué avant l'ovariectomie n'a pas protégé contre l'accumulation des graisses qu’entraîne l'ovariectomie, si celui-ci est interrompu après l'ovariectomie. Enfin, pour compléter les résultats antérieurs, nous avons montré dans la quatrième étude que l’expression des gènes impliqués dans la synthèse de lipide; SREBP-1c, SCD-1, ChREBP, et ACC dans le foie a augmenté après le retrait des œstrogènes, tandis qu’une diminution (P < 0.01) des niveaux d'ARNm de PPAR-α a été observée. De plus, l'expression hépatique des gènes des cytokines pro-inflammatoires incluant IKKβ, IL-6 ainsi que le contenu protéinique de NF-кB étaient augmentés (P < 0.01) chez les rates Ovx par rapport aux rates ayant subi une Ovx simulée (Sham). Toutes ces perturbations ont été améliorées avec la supplémentation en œstrogènes seulement, ainsi qu'avec l'entraînement en endurance seulement. Dans l'ensemble, nos résultats indiquent que l'exercice physique (en résistance ou en endurance) a un impact significatif sur la réduction de l'accumulation des lipides dans le foie et dans le tissu adipeux des rates Ovx. De plus, chez les rates Ovx, l’entraînement en endurance mimerait les effets des œstrogènes sur l'expression des gènes impliqués dans l'accumulation de lipides et l’inflammation préclinique dans le foie.

Indicators of success in the dietary management of overweight and obesity: weight, body fat loss and quality

Concepts: %WL: Percentage of weight loss; %FL: Percentage of fat loss. Objective: evaluate which unit of measurement for weight loss could determine the success or failure of dietary treatment for overweight and obesity. Method: 4,625 consultations carried out on 616 patients in the southeast of Spain from 2006 to 2012. All of the patients were over 25 years of age and suffered from overweight or obesity. The consultations were carried out every fortnight, using the Mediterranean or low-calorie diet. The patients were divided into four groups according to their %WL and %FL. Results: most of the sample consisted of: women; participants between 25-45 years of age; attended consultations for over a month and a half; obese. 80% of the patients obtained a %FL ≥ 5% (15.5 ± 12.8). The groups with a higher %FL obtained significant differences in weight loss (22.6 vs 11.2%, p = 0.000). The multinomial analysis shows significant differences between the groups with the highest %FL and the lowest %WL and %FL: sex (p = 0.006 vs p = 0.005), BMI (p = 0.010 vs p = 0.003) and attendance (p = 0.000 vs p = 0.000). Conclusion: the patients who lost < 5% of fat had higher initial parameters (percentage of weight and fat); most of the sample lost ≥ 5% of fat. This means that the method of personalised dietary treatment results in a high fat loss; fat is an indicator of the quality loss obtained. Recommendations: use the measurement of fat as a complementary unit of measurement to weight loss; establish a limit of 5% to evaluate such loss; and increase this type of research in any method of weight loss.

Consequences of smoking for body weight, body fat distribution, and insulin resistance

Our aim was to critically evaluate the relations among smoking, body weight, body fat distribution, and insulin resistance as reported in the literature. In the short term, nicotine increases energy expenditure and could reduce appetite, which may explain why smokers tend to have lower body weight than do nonsmokers and why smoking cessation is frequently followed by weight gain. In contrast, heavy smokers tend to have greater body weight than do light smokers or nonsmokers, which likely reflects a clustering of risky behaviors (eg, low degree of physical activity, poor diet, and smoking) that is conducive to weight gain. Other factors, such as weight cycling, could also be involved. In addition, smoking increases insulin resistance and is associated with central fat accumulation. As a result, smoking increases the risk of metabolic syndrome and diabetes, and these factors increase risk of cardiovascular disease. In the context of the worldwide obesity epidemic and a high prevalence of smoking, the greater risk of (central) obesity and insulin resistance among smokers is a matter of major concern

A Dose-Response Strategy Reveals Differences between Normal-Weight and Obese Men in Their Metabolic and Inflammatory Responses to a High-Fat Meal.

A dose-response strategy may not only allow investigation of the impact of foods and nutrients on human health but may also reveal differences in the response of individuals to food ingestion based on their metabolic health status. In a randomized crossover study, we challenged 19 normal-weight (BMI: 20-25 kg/m(2)) and 18 obese (BMI: >30 kg/m(2)) men with 500, 1000, and 1500 kcal of a high-fat (HF) meal (60.5% energy from fat). Blood was taken at baseline and up to 6 h postprandially and analyzed for a range of metabolic, inflammatory, and hormonal variables, including plasma glucose, lipids, and C-reactive protein and serum insulin, glucagon-like peptide-1, interleukin-6 (IL-6), and endotoxin. Insulin was the only variable that could differentiate the postprandial response of normal-weight and obese participants at each of the 3 caloric doses. A significant response of the inflammatory marker IL-6 was only observed in the obese group after ingestion of the HF meal containing 1500 kcal [net incremental AUC (iAUC) = 22.9 ± 6.8 pg/mL × 6 h, P = 0.002]. Furthermore, the net iAUC for triglycerides significantly increased from the 1000 to the 1500 kcal meal in the obese group (5.0 ± 0.5 mmol/L × 6 h vs. 6.0 ± 0.5 mmol/L × 6 h; P = 0.015) but not in the normal-weight group (4.3 ± 0.5 mmol/L × 6 h vs. 4.8 ± 0.5 mmol/L × 6 h; P = 0.31). We propose that caloric dose-response studies may contribute to a better understanding of the metabolic impact of food on the human organism. This study was registered at clinicaltrials.gov as NCT01446068.

Common variants near MC4R are associated with fat mass, weight and risk of obesity.

To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) = 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits.

A Dose-Response Strategy Reveals Differences between Normal-Weight and Obese Men in Their Metabolic and Inflammatory Responses to a High-Fat Meal.

A dose-response strategy may not only allow investigation of the impact of foods and nutrients on human health but may also reveal differences in the response of individuals to food ingestion based on their metabolic health status. In a randomized crossover study, we challenged 19 normal-weight (BMI: 20-25 kg/m(2)) and 18 obese (BMI: >30 kg/m(2)) men with 500, 1000, and 1500 kcal of a high-fat (HF) meal (60.5% energy from fat). Blood was taken at baseline and up to 6 h postprandially and analyzed for a range of metabolic, inflammatory, and hormonal variables, including plasma glucose, lipids, and C-reactive protein and serum insulin, glucagon-like peptide-1, interleukin-6 (IL-6), and endotoxin. Insulin was the only variable that could differentiate the postprandial response of normal-weight and obese participants at each of the 3 caloric doses. A significant response of the inflammatory marker IL-6 was only observed in the obese group after ingestion of the HF meal containing 1500 kcal [net incremental AUC (net iAUC) = 22.9 ± 6.8 pg/mL × 6 h, P = 0.002]. Furthermore, the net iAUC for triglycerides significantly increased from the 1000 to the 1500 kcal meal in the obese group (5.0 ± 0.5 mmol/L × 6 h vs. 6.0 ± 0.5 mmol/L × 6 h, P = 0.015) but not in the normal-weight group (4.3 ± 0.5 mmol/L × 6 h vs. 4.8 ± 0.5 mmol/L × 6 h, P = 0.31). We propose that caloric dose-response studies may contribute to a better understanding of the metabolic impact of food on the human organism. This study was registered at clinicaltrials.gov as NCT01446068.

Effect of crude protein and fat content of diets with similar indispensable amino acid profile on productive performance and egg quality of brown egg laying hens differing in initial body weight

In total of 504 Lohmann Brown hens were used to study the influence of the initial BW of the birds and the crude protein (CP) and fat content of the diet on performance and egg quality traits from 22 to 49 weeks of age. The experiment was completely randomized with 8 treatments arranged factorially with 2 initial BW (1,726 vs. 1,987g) and 4 diets with similar AMEn (2,750 kcal AMEn/ kg) and indispensable (lys, Met+Cys, Thr, and Trp) amino acid contents.

Primary antiphospholipid syndrome in premenopausal women: low vitamin D, high fat mass and maintained bone mineral mass

The aim of this study was to analyze vitamin D levels and their association with bone mineral density and body composition in primary antiphospholipid syndrome. For this cross-sectional study 23 premenopausal women with primary antiphospholipid syndrome (Sapporo criteria) and 23 age- and race-matched healthy controls were enrolled. Demographic, anthropometric, clinical and laboratorial data were collected using clinical interview and chart review. Serum 25-hydroxyvitamin D levels, parathormone, calcium and 24-hour urinary calcium were evaluated in all subjects. Bone mineral density and body composition were studied by dual X-ray absorptiometry. The mean age of patients and controls was 33 years. Weight (75.61 [20.73] vs. 63.14 [7.34] kg, p=0.009), body mass index (29.57 [7.17] vs. 25.35 [3.37] kg, p=0.014) and caloric ingestion (2493 [1005.6] vs. 1990 [384.1] kcal/day, p=0.03) were higher in PAPS than controls. All PAPS were under oral anticoagulant with INR within therapeutic range. Interestingly, biochemical bone parameters revealed lower levels of 25-hydroxyvitamin D [21.64 (11.26) vs. 28.59 (10.67) mg/dl, p=0.039], serum calcium [9.04 (0.46) vs. 9.3 (0.46) mg/dl, p=0.013] and 24-hour urinary calcium [106.55 (83.71) vs. 172.92 (119.05) mg/d, p=0.027] in patients than in controls. Supporting these findings, parathormone levels were higher in primary antiphospholipid syndrome than in controls [64.82 (37.83) vs. 44.53 (19.62) pg/ml, p=0.028]. The analysis of osteoporosis risk factors revealed that the two groups were comparable (p>0.05). Lumbar spine, femoral neck, total femur and whole body bone mineral density were similar in both groups (p>0.05). Higher fat mass [28.51 (12.93) vs. 20.01 (4.68) kg, p=0.005] and higher percentage of fat [36.08 (7.37) vs. 31.23 (4.64)%, p=0.010] were observed in PAPS in comparison with controls; although no difference was seen regarding lean mass. In summary, low vitamin D in primary antiphospholipid syndrome could be secondary to higher weight and fat mass herein observed most likely due to adipocyte sequestration. This weight gain may also justify the maintenance of bone mineral density even with altered biochemical bone parameters. Lupus (2010) 19, 1302-1306.

Effect of angiotensin converting enzyme inhibitor enalapril on body weight and composition in young rats

Obesity is considered a worldwide public health problem showing an increased prevalence in developing countries, with urgent need for new and more efficient drugs and therapies. Enalapril, an angiotensin-I converting enzyme inhibitor (ACEi), is classically used in antihypertensive therapies, however, earlier publications have shown that this drug could also have significant impact on body weight in rats as well as in humans, besides reducing blood pressure. The effect of this drug in the white adipose tissue has been neglected for long time, even considering that most components of the renin-angiotensin and kallikrein-kinin system are expressed in this tissue. Furthermore, the adipose tissue is considered today as one of the most important sites for endocrine/inflammatory regulation of appetite and energy output and AngII has been linked to the metabolism in this tissue. Therefore, we analyzed the influence of chronic enalapril treatment in normotensive rats at earlier ages, evaluating body weight, energy homeostasis, lipid profile and serum levels of the hormones leptin and insulin, in the presence of a standard or a palatable hyperlipidic diet regimen for one month. Our results show that enalapril treatment is able to reduce body fat on both diets, without alteration in serum lipid profile. Furthermore, animals receiving enalapril showed reduction in food intake, leptin level and energy intake. In summary, these findings show for the first time that the ACEi enalapril reduces body fat in young normotensive rats and highlights a novel target to treat obesity and associated diseases. (c) 2007 Elsevier B.V. All rights reserved.

Early Markers of Atherosclerotic Disease in Individuals with Excess Weight and Dyslipidemia

Abstract Background: Excessive weight is a cardiovascular risk factor since it generates a chronic inflammatory process that aggravates the endothelial function. Objective: To evaluate the endothelial function in individuals with excess weight and mild dyslipidemia using brachial artery flow-mediated dilation (BAFMD), and the association of endothelial function with anthropometric and biochemical variables. Methods: Cross-sectional study that included 74 individuals and evaluated anthropometric variables (body mass index [BMI], waist-hip ratio [WHR], waist circumference [AC], and percentage of body fat [PBF]), biochemical (blood glucose, insulinemia, ultrasensitive C-reactive protein, fibrinogen, total cholesterol, HDL-cholesterol, triglycerides, and LDL-cholesterol) and endothelial function (BAFMD, evaluated by ultrasound). The statistical analysis was performed with SPSS, version 16.0. To study the association between the variables, we used chi-square, Student's t and Mann-Whitney tests, and Pearson's correlation. Logistic regression analyzed the independent influence of the factors. Values of p < 0.05 were considered significant. Results: The participants had a mean age of 50.8 years, and 57% were female. BMI, WC, WHR, and PBF showed no significant association with BAFMD. The male gender (p = 0.02) and higher serum levels of fibrinogen (p = 0.02) were significantly and independently associated with a BAFMD below 8%. Conclusions: In individuals with excess weight and mild untreated dyslipidemia, male gender and higher levels of fibrinogen were independently associated with worse BAFMD.

Influence of CRTC1 Polymorphisms on Body Mass Index and Fat Mass in Psychiatric Patients and the General Adult Population.

IMPORTANCE There is a high prevalence of obesity in psychiatric patients, possibly leading to metabolic complications and reducing life expectancy. The CREB-regulated transcription coactivator 1 (CRTC1) gene is involved in energy balance and obesity in animal models, but its role in human obesity is unknown. OBJECTIVE To determine whether polymorphisms within the CRTC1 gene are associated with adiposity markers in psychiatric patients and the general population. DESIGN, SETTING, AND PARTICIPANTS Retrospective and prospective data analysis and population-based samples at Lausanne and Geneva university hospitals in Switzerland and a private clinic in Lausanne, Switzerland. The effect of 3 CRTC1 polymorphisms on body mass index (BMI) and/or fat mass was investigated in a discovery cohort of psychiatric outpatients taking weight gain-inducing psychotropic drugs (sample 1, n = 152). The CRTC1 variant that was significantly associated with BMI and survived Bonferroni corrections for multiple comparison was then replicated in 2 independent psychiatric samples (sample 2, n = 174 and sample 3, n = 118) and 2 white population-based samples (sample 4, n = 5338 and sample 5, n = 123 865). INTERVENTION Noninterventional studies. MAIN OUTCOME AND MEASURE Difference in BMI and/or fat mass between CRTC1 genotype groups. RESULTS Among the CRTC1 variants tested in the first psychiatric sample, only rs3746266A>G was associated with BMI (Padjusted = .003). In the 3 psychiatric samples, carriers of the rs3746266 G allele had a lower BMI than noncarriers (AA genotype) (sample 1, P = .001; sample 2, P = .05; and sample 3, P = .0003). In the combined analysis, excluding patients taking other weight gain-inducing drugs, G allele carriers (n = 98) had a 1.81-kg/m2 lower BMI than noncarriers (n = 226; P < .0001). The strongest association was observed in women younger than 45 years, with a 3.87-kg/m2 lower BMI in G allele carriers (n = 25) compared with noncarriers (n = 48; P < .0001), explaining 9% of BMI variance. In the population-based samples, the T allele of rs6510997C>T (a proxy of the rs3746266 G allele; r2 = 0.7) was associated with lower BMI (sample 5, n = 123 865; P = .01) and fat mass (sample 4, n = 5338; P = .03). The strongest association with fat mass was observed in premenopausal women (n = 1192; P = .02). CONCLUSIONS AND RELEVANCE These findings suggest that CRTC1 contributes to the genetics of human obesity in psychiatric patients and the general population. Identification of high-risk subjects could contribute to a better individualization of the pharmacological treatment in psychiatry.

Neuroendocrine characterization and anorexigenic effects of telmisartan in diet- and glitazone-induced weight gain.

Telmisartan is an angiotensin II receptor blocker with peroxisome proliferator-activated receptor-gamma agonistic properties. Telmisartan prevents weight gain and decreases food intake in models of obesity and in glitazone-treated rodents. This study further investigates the influence of telmisartan and pioglitazone and their association on weight gain and body composition by examining their influence on neuroendocrine mediators involved in food intake. Male C57/Black 6 mice were fed a high-fat diet, weight matched, and randomized in 4 treatment groups: vehicle, pioglitazone, telmisartan, and pioglitazone-telmisartan. Weight gain, food and water intake, body composition, plasma leptin levels, and the hypothalamic expression of neuroendocrine mediators were analyzed. Additional studies were performed with irbesartan and in angiotensin II 1(A) receptor-knockout mice. Telmisartan abolished weight and fat gain in vehicle- and pioglitazone-treated mice while decreasing food intake, the hypothalamic expression of the agouti-related protein, and plasma leptin levels. Modifications in neuropeptide Y and proopiomelanocortin were not consistent with changes in food intake. The effects on weight gain and expression of the agouti-related protein were intermediate with irbesartan. The effects of telmisartan on weight gain were even more pronounced in angiotensin II 1(A) receptor-knockout mice. This study confirms the anorexigenic effects of telmisartan in mice fed a high-fat diet and suggests for the first time a functional role of telmisartan on hypothalamic orexigenic agouti-related protein regulation. These anorexigenic properties abolish both weight gain and body composition modifications in fat-fed and glitazone-treated mice. The anorexigenic properties are independent from the angiotensin II 1(A) receptor.

Depression with atypical features and increase in obesity, body mass index, waist circumference, and fat mass: a prospective, population-based study.

IMPORTANCE: Depression and obesity are 2 prevalent disorders that have been repeatedly shown to be associated. However, the mechanisms and temporal sequence underlying this association are poorly understood. OBJECTIVE: To determine whether the subtypes of major depressive disorder (MDD; melancholic, atypical, combined, or unspecified) are predictive of adiposity in terms of the incidence of obesity and changes in body mass index (calculated as weight in kilograms divided by height in meters squared), waist circumference, and fat mass. DESIGN, SETTING, AND PARTICIPANTS: This prospective population-based cohort study, CoLaus (Cohorte Lausannoise)/PsyCoLaus (Psychiatric arm of the CoLaus Study), with 5.5 years of follow-up included 3054 randomly selected residents (mean age, 49.7 years; 53.1% were women) of the city of Lausanne, Switzerland (according to the civil register), aged 35 to 66 years in 2003, who accepted the physical and psychiatric baseline and physical follow-up evaluations. EXPOSURES: Depression subtypes according to the DSM-IV. Diagnostic criteria at baseline and follow-up, as well as sociodemographic characteristics, lifestyle (alcohol and tobacco use and physical activity), and medication, were elicited using the semistructured Diagnostic Interview for Genetic Studies. MAIN OUTCOMES AND MEASURES: Changes in body mass index, waist circumference, and fat mass during the follow-up period, in percentage of the baseline value, and the incidence of obesity during the follow-up period among nonobese participants at baseline. Weight, height, waist circumference, and body fat (bioimpedance) were measured at baseline and follow-up by trained field interviewers. RESULTS: Only participants with the atypical subtype of MDD at baseline revealed a higher increase in adiposity during follow-up than participants without MDD. The associations between this MDD subtype and body mass index (β = 3.19; 95% CI, 1.50-4.88), incidence of obesity (odds ratio, 3.75; 95% CI, 1.24-11.35), waist circumference in both sexes (β = 2.44; 95% CI, 0.21-4.66), and fat mass in men (β = 16.36; 95% CI, 4.81-27.92) remained significant after adjustments for a wide range of possible cofounding. CONCLUSIONS AND RELEVANCE: The atypical subtype of MDD is a strong predictor of obesity. This emphasizes the need to identify individuals with this subtype of MDD in both clinical and research settings. Therapeutic measures to diminish the consequences of increased appetite during depressive episodes with atypical features are advocated.