Impact of sex, fat distribution and initial body weight on oxytocin's body weight regulation.
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ABSTRACT:
SUBMITTER: Maejima Y
PROVIDER: S-EPMC5561196 | biostudies-other | 2017 Aug
REPOSITORIES: biostudies-other
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Project description:BackgroundObesity is an important cause of multiple cancer types, amongst which endometrial cancer (EC). The relation between obesity and cancer is complicated and involves alterations in insulin metabolism, response to inflammation and alterations in estradiol metabolism. Visceral obesity is assumed to play the most important role in the first two mechanisms, but its role in estradiol metabolism is unclear. Therefore, this retrospective study explores the relationship of body mass index (BMI), visceral fat volume (VAV) and subcutaneous fat volume (SAV) and serum levels of sex steroids and lipids in patients with endometrial cancer.MethodsThirty-nine postmenopausal EC patients with available BMI, blood serum and Computed Tomography (CT) scans were included. Serum was analyzed for estradiol, dehydroepiandrosterone sulfate (DHEAS), androstenedione, testosterone, cholesterol, triglycerides and high (HDL), low (LDL) and non-high density (NHDL) lipoprotein. VAV and SAV were quantified on abdominal CT scan images. Findings were interpreted using pearson correlation coefficient and linear regression with commonality analysis.ResultsSerum estradiol is moderately correlated with BMI (r = 0.62) and VAV (r = 0.58) and strongly correlated with SAV (r = 0.74) (p < 0.001 for all). SAV contributes more to estradiol levels than VAV (10.3% for SAV, 1.4% for VAV, 35.9% for SAV and VAV, p = 0.01). Other sex steroids and lipids have weak and moderate correlations with VAV or SAV.ConclusionsThis study shows that serum estradiol is correlated with BMI and other fat-distribution measures in postmenopausal endometrial cancer patients. Subcutaneous fat tissue contributes more to the estradiol levels indicating that subcutaneous fat might be relevant in endometrial cancer carcinogenesis.
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Project description:Increased plasma and adipose tissue protease activity is observed in patients with type 2 diabetes and obesity. It has been proposed that specific proteases contribute to the link between obesity, adipose tissue inflammation and metabolic diseases. We have recently shown that ablation of the serine protease kallikrein-related peptidase 7 (Klk7) specifically in adipose tissue preserves systemic insulin sensitivity and protects mice from obesity-related AT inflammation. Here, we investigated whether whole body Klk7 knockout (Klk7-/-) mice develop a phenotype distinct from that caused by reduced Klk7 expression in adipose tissue. Compared to littermate controls, Klk7-/- mice gain less body weight and fat mass both under chow and high fat diet (HFD) feeding, are hyper-responsive to exogenous insulin and exhibit preserved adipose tissue function due to adipocyte hyperplasia and lower inflammation. Klk7-/- mice exhibit increased adipose tissue thermogenesis, which is not related to altered thyroid function. These data strengthen our recently proposed role of Klk7 in the regulation of body weight, energy metabolism, and obesity-associated adipose tissue dysfunction. The protective effects of Klk7 deficiency in obesity are likely linked to a significant limitation of adipocyte hypertrophy. In conclusion, our data indicate potential application of specific KLK7 inhibitors to regulate KLK7 activity in the development of obesity and counteract obesity-associated inflammation and metabolic diseases.
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Project description:Although obesity is considered osteoprotective, the effects of body fat and fat distribution on bone tissue after adjusting for the effects of body weight remain uncertain. This study evaluated the relationships between fat mass, fat distribution, and bone mineral status beyond its weight-bearing effect. We recruited 466 children aged 6-10 years in China. Dual-energy X-ray absorptiometry was used to determine the bone mineral density (BMD) and bone mineral content (BMC) in the total body and total body less head (TBLH), as well as the fat mass (FM) and percentage fat mass (%FM) of the total and segmental body. Weight-adjusted measures of FM and %FM were derived using the residual method. After adjusting for the effects of covariates, we observed statistically significant, dose-dependent negative relationships between the TBLH·BMD/BMC and various weight-adjusted measures of body fat (p for trend: <0.001-0.038). For each standard deviation increment in the weight-adjusted total body, TBLH, trunk and limbs, the size-adjusted BMC decreased approximately 9.44, 9.28, 8.13, and 6.65 g in boys, respectively, and by approximately 13.74, 13.71, 7.84, and 12.95 g in girls, respectively. Significant inverse associations between FM accumulation in the total body and most body parts with the BMD/BMC were observed in both boys and girls after adjusting for weight and potential confounders.
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Project description:The purpose was to determine whether lifestyle interventions have different effects on regional fat in women with normal glucose tolerance vs. impaired glucose tolerance (NGT vs. IGT).Changes in glucose metabolism (2-h oral glucose-tolerance tests), android to gynoid fat mass ratio (dual energy X-ray absorptiometry [DXA]), visceral to subcutaneous abdominal fat area ratio (CT), and abdominal to gluteal subcutaneous fat cell weight (FCW; adipose tissue biopsies) were determined in 60 overweight postmenopausal women (45-80 years) following 6 months of weight loss alone (WL; n = 28) or with aerobic exercise (AEX + WL; n = 32).The interventions led to ?8% decrease in weight, but only the AEX + WL group improved fitness (?11% in VO2max) and reduced the android-to-gynoid fat mass ratio (?5%; p < 0.05). Both NGT and IGT groups reduced visceral and subcutaneous abdominal fat areas and abdominal and gluteal FCWs, which related to improvements in homeostatic model assessment (r = 0.34-0.42) and 2-h glucose (r = 0.34-0.35), respectively (p < 0.05). The decline in FCW was 2× greater in women with IGT following WL (p < 0.05). The ratios of abdominal-to-gluteal FCW did not change following either intervention.The mechanisms by which WL with and without exercise impact regional fat loss should be explored as reductions in abdominal fat area and subcutaneous FCW appear to influence glucose metabolism. This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply. Published by S. Karger AG, Basel.
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Project description:Obesity is known to decrease the efficacy of neoadjuvant chemotherapy (NAC) against breast cancer; however, the relationship between actual body composition and NAC outcomes remains unknown. Therefore, we determined the effect of body composition on NAC outcomes. A total of 172 advanced breast cancer patients who underwent surgery after NAC were retrospectively analyzed. Body composition parameters including abdominal circumference (AC), subcutaneous fat area (SFA), visceral fat area (VFA), and skeletal muscle area (SMA) were calculated using computed tomography volume-analyzing software. VFA/SFA ratio was used to evaluate visceral obesity. The associations of body composition parameters with pathological complete remission (pCR) and survival were analyzed. AC, SFA, and VFA were significantly correlated with body mass index (BMI) (all P < 0.05; r = 0.82, r = 0.71, and r = 0.78, respectively). AC, SFA, and VFA increased significantly and SMA decreased significantly after menopause (all P < 0.05). VFA/SFA ratio increased significantly after menopause, even though BMI remained unchanged. Body composition parameters were not associated with pCR. Distant disease-free survival (DDFS) was significantly worse in the high VFA group than in the low VFA group (P < 0.05). Furthermore, in the high VFA group, postmenopausal patients had significantly shorter DDFS than premenopausal patients (P < 0.05). VFA was independently associated with DDFS in the multivariate analysis (P < 0.05). High visceral fat is associated with worse NAC outcomes in breast cancer patients, especially postmenopausal patients. Interventions targeting visceral fat accumulation will likely improve NAC outcomes.
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Project description:Body mass and body fat composition are of clinical interest due to their links to cardiovascular- and metabolic diseases. Fat stored in the trunk has been suggested to be more pathogenic compared to fat stored in other compartments. In this study, we perform genome-wide association studies (GWAS) for the proportion of body fat distributed to the arms, legs and trunk estimated from segmental bio-electrical impedance analysis (sBIA) for 362,499 individuals from the UK Biobank. 98 independent associations with body fat distribution are identified, 29 that have not previously been associated with anthropometric traits. A high degree of sex-heterogeneity is observed and the effects of 37 associated variants are stronger in females compared to males. Our findings also implicate that body fat distribution in females involves mesenchyme derived tissues and cell types, female endocrine tissues as well as extracellular matrix maintenance and remodeling.
| S-EPMC6341104 | biostudies-literature
Project description:BackgroundAlthough obesity is an established modifiable risk factor for multiple myeloma (MM), several nuanced aspects of its relation to MM remain unelucidated, limiting public health and prevention messages.MethodsWe analyzed prospective data from the Nurses' Health Study and Health Professionals Follow-Up Study to examine MM risk associated with 20-year weight patterns in adulthood, body shape trajectory from ages 5 to 60 years, and body fat distribution. For each aforementioned risk factor, we report hazard ratios (HRs) and 95% confidence intervals (CIs) for incident MM from multivariable Cox proportional-hazards models.ResultsWe documented 582 incident MM cases during 4 280 712 person-years of follow-up. Persons who exhibited extreme weight cycling, for example, those with net weight gain and one or more episodes of intentional loss of at least 20 pounds or whose cumulative intentional weight loss exceeded net weight loss with at least one episode of intentional loss of 20 pounds or more had an increased MM risk compared with individuals who maintained their weight (HR = 1.71, 95% CI = 1.05 to 2.80); the association was statistically nonsignificant after adjustment for body mass index. We identified four body shape trajectories: lean-stable, lean-increase, medium-stable, and medium-increase. MM risk was higher in the medium-increase group than in the lean-stable group (HR = 1.62, 95% CI = 1.22 to 2.14). Additionally, MM risk increased with increasing hip circumference (HR per 1-inch increase: 1.03, 95% CI = 1.01 to 1.06) but was not associated with other body fat distribution measures.ConclusionsMaintaining a lean and stable weight throughout life may provide the strongest benefit in terms of MM prevention.
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Project description:The prevalence of obesity has been increasing markedly in the U.S. and worldwide in the past decades; and notably, the obese populations are signified by not only the overall elevated adiposity but also particularly harmful accumulation of body fat in the central region of the body, namely, abdominal obesity. The profound shift from "traditional" to "obesogenic" environments, principally featured by the abundance of palatable, energy-dense diet, reduced physical activity, and prolonged sedentary time, promotes the obesity epidemics and detrimental body fat distribution. Recent advances in genomics studies shed light on the genetic basis of obesity and body fat distribution. In addition, growing evidence from investigations in large cohorts and clinical trials has lent support to interactions between genetic variations and environmental factors, e.g., diet and lifestyle factors, in relation to obesity and body fat distribution. This review summarizes the recent discoveries from observational studies and randomized clinical trials on the gene-environment interactions on obesity and body fat distribution.
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Project description:It is recognized that higher height and weight are associated with higher risk of atrial fibrillation or flutter (AF) but it is unclear whether risk of AF is related to body fat, body fat location, or lean body mass.This article reports the Danish population-based prospective cohort Diet, Cancer and Health study conducted among 55,273 men and women 50-64 years of age at recruitment. The associations between bioelectrical impedance derived measures of body composition and combinations of anthropometric measures of body fat distribution and risk of an incident record of AF in the Danish Registry of Patients were investigated.During follow-up (median 13.5 years) AF developed in 1,669 men and 912 women. Higher body fat at any measured location was associated with higher risk of AF. The adjusted hazard ratio (HR) per 1 sex-specific standard deviation (SD) increment in body fat mass was 1.29 (95% confidence interval [CI], 1.24-1.33). Higher lean body mass was also associated with a higher risk of AF. The adjusted HR for 1 sex-specific SD increment was 1.40 (95% CI, 1.35-1.45).Higher body fat and higher lean body mass were both associated with higher risk of AF.
| S-EPMC4169701 | biostudies-literature
Project description:BackgroundAdiposity and mitochondrial dysfunction are related factors contributing to metabolic disease development. This pilot study examined whether in vivo and ex vivo indices of mitochondrial metabolism were differentially associated with body composition in males and females.MethodsThirty-four participants including 19 females (mean 27 yr) and 15 males (mean 29 yr) had body composition assessed by dual energy x-ray absorptiometry and magnetic resonance (MR) imaging. Monocyte reserve capacity and maximal oxygen consumption rate (OCR) were determined ex vivo using extracellular flux analysis. In vivo quadriceps mitochondrial function was measured using 31P-MR spectroscopy based on post-exercise recovery kinetics (τPCr). The homeostatic model assessment of insulin resistance (HOMA-IR) was calculated from fasting glucose and insulin levels. Variables were log-transformed, and Pearson correlations and partial correlations were used for analyses.ResultsMitochondrial metabolism was similar between sexes (p > 0.05). In males only, higher fat mass percent (FM%) was correlated with lower reserve capacity (r = - 0.73; p = 0.002) and reduced muscle mitochondrial function (r = 0.58, p = 0.02). Thigh subcutaneous adipose tissue was inversely related to reserve capacity in males (r = - 0.75, p = 0.001), but in females was correlated to higher maximal OCR (r = 0.48, p = 0.046), independent of FM. In females, lean mass was related to greater reserve capacity (r = 0.47, p = 0.04). In all participants, insulin (r = 0.35; p = 0.04) and HOMA-IR (r = 0.34; p = 0.05) were associated with a higher τPCr.ConclusionsThese novel findings demonstrate distinct sex-dependent associations between monocyte and skeletal muscle mitochondrial metabolism with body composition. With further study, increased understanding of these relationships may inform sex-specific interventions to improve mitochondrial function and metabolic health.
| S-EPMC9123728 | biostudies-literature