Increase In Visceral Adiposity Research Articles

Abstract PO5-09-11: Abrupt involution of mouse mammary gland leads to inflammatory systemic changes along with mammary specific metabolic shifts that may enhance risk of breast cancer

Abstract Epidemiological data links higher parity and lack of breastfeeding with increased risk of breast cancer, specifically aggressive triple negative breast cancer (TNBC), and higher mortality rate. Following pregnancy and lactation, breast remodels to near pre-pregnancy stage through apoptotic cell death and adipocyte repopulation process. Long-term breastfeeding and gradual weaning of an infant leads to gradual involution (GI) of the breast, while lack of or abrupt discontinuation of breastfeeding after birth leads to abrupt involution (AI), when rapid and massive cell death takes place. Our studies have shown several precancerous changes, such as increased collagen deposition, inflammation, and hyperplasia in the mammary gland of mice after AI. However, the systemic impact of AI and how this increases risk of breast cancer is yet to be elucidated. Objectives: Our objective is to evaluate the systemic effects that are prompted by the AI mammary gland. We hypothesize that AI leads to marked alteration in lipid metabolism and systemic inflammation that enhances risk for breast cancer. Methods: FVB/n mice (8week old) were paired for breeding. At partum (day 0), dams were randomized to AI or GI cohort and standardized to 6 pups. AI mice had pups removed on day 7 postpartum (ppm) to mimic short-term breastfeeding. For GI mice 3 pups each were removed on day 28 and 31ppm to mimic gradual weaning. Tissues harvested on day 28, 56, and 120 postpartum. Body composition was measured by echo MRI. Glucose tolerance test (GTT) was performed after a 6 hour fast using a 2g/kg glucose intraperitoneal injection. Blood glucose was measured by glucometer. Serum insulin was analyzed by ELISA. HOMA-IR was calculated using blood glucose and serum insulin results. Serum was analyzed using multiplex ELISA by MesoScale Diagnostics. Mammary glands were subjected to untargeted lipidomics. Results: There were no significant differences in body weight, percent body fat or lean mass between AI and GI groups at any time point. However, at day 120 ppm (4 months after partum), we have observed significantly larger amount (1.29-fold increase) of perigonadal adipose tissue (visceral adipose) in AI mice than GI mice (p=0.0112; n=24-38/group). There were no significant differences in blood glucose, serum insulin, HOMA-IR, or GTT results between AI and GI groups at day 120. AI mice had significantly higher levels of cytokines IL-1β (3.1-fold increase, p=0.0417) and KC/GRO (1.5-fold increase, p=0.0196) than GI mice at day 120. At day 28, AI mammary glands had significantly higher amounts of level 3 identified oxidized ceramide containing sphingolipids that were linked to insulin resistance and diabetes. At day 56, GI mammary glands had significantly higher amounts of level 2 and 3 identified metabolites linked to cellular signaling and lipid metabolism. On day 120, there were no significant differences in lipid metabolites between groups. Conclusion: Although histologically GI and AI mammary glands return to near pre-pregnancy state within a month after partum, our data shows specific lipid changes in the AI mammary gland similar to what has been shown in women with TNBC. Furthermore, AI of the mammary gland leads to systemic effects on adiposity and inflammation that could be key to increased breast cancer risk. Further studies along these lines are in progress to understand the whole-body effects of AI and stratify preventive measures for women who cannot breast feed. Significance: Lack of breastfeeding is more prevalent in African American (AA) women and linked to higher risk of developing aggressive TNBC1. Our novel animal models of AI and GI help to link the impact of AI and systemic changes that may enhance breast cancer risk. In particular, we see an increase in visceral adiposity with AI. Understanding this mechanism will help identify strategies to reduce risk in women who are unable or choose not to breastfeed and ultimately help to reduce TNBC and TNBC-related mortality in AA women. Citation Format: Kate Ormiston, Kirti Kaul, Neelam Shinde, Djawed Bennouna, Rachel Kopec, Ramesh Ganju, Sarmila Majumder, Bhuvaneswari Ramaswamy. Abrupt involution of mouse mammary gland leads to inflammatory systemic changes along with mammary specific metabolic shifts that may enhance risk of breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-09-11.

Visceral Adiposity and Progression of ADPKD: A Cohort Study of Patients From the TEMPO 3:4 Trial

Rationale & ObjectiveBody-mass index (BMI) is an independent predictor of kidney disease progression in individuals with autosomal dominant polycystic kidney disease (ADPKD). Adipocytes do not simply act as a fat reservoir but are active endocrine organs. We hypothesized that greater visceral abdominal adiposity would associate with more rapid kidney growth in ADPKD and influence the efficacy of tolvaptan. Study DesignA retrospective cohort study. Setting & Participants1053 patients enrolled in the TEMPO 3:4 tolvaptan trial with ADPKD and high risk of rapid disease progression. PredictorEstimates of visceral adiposity extracted from coronal plane MRIs using deep learning. OutcomeAnnual change in total kidney volume (TKV) and effect of tolvaptan on kidney growth. Analytical ApproachMultinomial logistic regression and linear mixed models. ResultsIn fully adjusted models, the highest tertile of visceral adiposity was associated with greater odds of annual change in TKV of ≥7% vs. <5% (OR: 4.78 [3.03, 7.47]). The association was stronger in females than males (interaction p<0.01). In linear mixed models with an outcome of % change in TKV per year, tolvaptan efficacy (% change in TKV) was reduced with higher visceral adiposity (three-way interaction of treatment*time*visceral adiposity p=0.002). Visceral adiposity significantly improved classification performance of predicting rapid annual % change in TKV for individuals with a normal BMI (De-Long’s test Z-score: -2.03; p=0.04). Greater visceral adiposity was not associated with estimated glomerular filtration rate (eGFR) slope in the overall cohort; however, visceral adiposity was associated with more rapid decline in eGFR slope (below the median) in females (fully adjusted OR 1.06 [1.01, 1.11] per 10 unit increase in visceral adiposity) but not males (0.98 [0.95, 1.02]). LimitationsRetrospective; rapid progressors; computational demand of deep learning. ConclusionsVisceral adiposity that can be quantified by MRI in the coronal plane using a deep learning segmentation model, independently associates with more rapid kidney growth, and improves classification of rapid progression in individuals with a normal BMI. Tolvaptan efficacy decreases with increasing visceral adiposity.

Abdominal Body Composition Reference Ranges and Association With Chronic Conditions in an Age- and Sex-Stratified Representative Sample of a Geographically Defined American Population.

Body composition can be accurately quantified from abdominal computed tomography (CT) exams and is a predictor for the development of aging-related conditions and for mortality. However, reference ranges for CT-derived body composition measures of obesity, sarcopenia, and bone loss have yet to be defined in the general population. We identified a population-representative sample of 4900 persons aged 20 to 89 years who underwent an abdominal CT exam from 2010 to 2020. The sample was constructed using propensity score matching an age and sex stratified sample of persons residing in the 27-county region of Southern Minnesota and Western Wisconsin. The matching included race, ethnicity, education level, region of residence, and the presence of 20 chronic conditions. We used a validated deep learning based algorithm to calculate subcutaneous adipose tissue area, visceral adipose tissue area, skeletal muscle area, skeletal muscle density, vertebral bone area, and vertebral bone density from a CT abdominal section. We report CT-based body composition reference ranges on 4649 persons representative of our geographic region. Older age was associated with a decrease in skeletal muscle area and density, and an increase in visceral adiposity. All chronic conditions were associated with a statistically significant difference in at least one body composition biomarker. The presence of a chronic condition was generally associated with greater subcutaneous and visceral adiposity, and lower muscle density and vertebrae bone density. We report reference ranges for CT-based body composition biomarkers in a population-representative cohort of 4649 persons by age, sex, body mass index, and chronic conditions.

Antioxidative Effects of Black Currant and Cornelian Cherry Juices in Different Tissues of an Experimental Model of Metabolic Syndrome in Rats.

A Western-style diet, rich in fat and simple sugars, is the main risk factor for a significant number of chronic diseases and disorders, as well as for a progression of metabolic syndrome (MetS). One of the key mechanisms involved in MetS development is increased oxidative stress caused by the accumulation of body fat. Some dietary polyphenols have shown a protective role in preventing oxidative-stress-induced damage. We investigated the difference in the oxidative response of plasma, liver, and visceral adipose tissue in rats fed with a high-fat high-fructose (HFF) diet for ten weeks, and the effectiveness of polyphenol-rich juices (black currant (BC) and cornelian cherry (CC)) in HFF-diet-induced oxidative stress prevention. The most prominent impact of the HFF diet on redox parameters was recorded in the liver, whereas adipose tissue showed the most potent protection mechanisms against oxidative stress. Consumption of both juices decreased advanced oxidation protein product (AOPP) level in plasma, increased paraoxonase1 (PON1) activity in the liver, and significantly decreased total oxidative status (TOS) in adipose tissue. BC exerted stronger antioxidative potential than CC and decreased the superoxide anion radical (O2•-) level in the liver. It also reduced TOS, total antioxidative status (TAS), and malondialdehyde (MDA) concentration in adipose tissue. The multiple linear regression analysis has shown that the best predictors of MetS development, estimated through the increase in visceral adiposity, were superoxide dismutase (SOD), AOPP, TOS, and TAS. The consumption of polyphenol-rich juices may provide a convenient approach for the systemic reduction of oxidative stress parameters.

Six months of aerobic exercise training does not prevent a worsening of glucose tolerance in individuals with acute spinal cord injury

Individuals with spinal cord injuries (SCI) have a greater incidence of Type 2 Diabetes (T2D) than their non-injured peers. The increased incidence of T2D has been noted in individuals within the first few years after injury, and incidence increases with time since injury. Aerobic exercise training improves long-term glycemic control in non-injured individuals and results in improved glycemic control in individuals with chronic SCI (&gt;10 years). However, it is unknown whether individuals with acute injuries (&lt;3 years) display altered glucose control, and if aerobic training may prevent worsening of glucose control and T2D. Therefore, we assessed blood glucose regulation in individuals &lt;3 years post SCI injury. Glucose regulation was assessed through fasting blood glucose, insulin, hemoglobin A1C (HbA1C), homeostatic model assessment for insulin resistance (HOMA-IR), and an oral glucose tolerance test (OGTT). In addition, body composition was estimated via dual energy x-ray absorptiometry. These assessments were made prior to, and following 3- and 6-months (mo) of aerobic exercise training consisting of hybrid functional electrical stimulation rowing. Data were analyzed with 1-way RMANOVA. Eight individuals (1F, 7M, age 20-45 years) with SCI 9-27 mo post-injury and a neurological level of injury from spinal cord segments C3 to T3 were enrolled. Individuals exercised for 30min per session, at ~60% VO2peak, 2-3 times per week. Fasting glucose (Pre:85±9, 3m:88±8, 6m:86±2 mg/dL, p=0.55), insulin (Pre:6.0±3.8, 3m:5.7±2.5, 6m:3.9±2.5 uIU/mL, p=0.25), HbA1C (Pre:4.9±0.3, 3m:5.0±0.3, 6m:4.8±0.1%, p=0.73) and HOMA-IR (Pre:1.4±1.0, 3m:1.2±0.7, 6m:0.7±0.4, p=0.26) did not change after 6-mo of training. In contrast, the dynamic assessment of glucose tolerance (OGTT) showed dramatic worsening (AUC Pre:15.7±3.8, 3m:17.8±5.9, 6m:17.6±5.8 units, p=0.04) from pre-exercise to 3-mo. Moreover, following 6-mo of exercise training, 1 individual met the diagnostic criteria for impaired glucose tolerance and another 2 for diabetes. Exercise training did not change visceral adipose mass (Pre:1.4±0.9, 3m:1.4±1.2, 6m:1.3±1.2 kg, p=0.96) or total body lean mass (Pre:50.4±9.5, 3m:49.6±9.6, 6m:49.5±9.5kg, p=0.98). These results suggest that fasting measures alone are not sensitive enough in detecting impairments in glucose metabolism in the acute period following a SCI. Interestingly, in people with SCI, whole-body aerobic exercise does not prevent the occurrence of impaired glucose metabolism. The worsening of glucose tolerance occurs despite a conservation of lean mass and no increase in visceral adiposity. It will be of importance to determine the mechanisms underlying the worsening of glycemic control and develop therapies to prevent metabolic disease in SCI. R01 HL117037, F32 HL156675 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Serum levels of Nitric Oxide metabolites in relation to Body Mass Index and Arterial stiffness in young individuals

Introduction: Obesity is a multi-factorial disorder defined as abnormally high levels of body fat accumulation. It is a major emerging pandemic of this century which can be attributed to alterations in eating habits, lifestyle choices and rise in sedentary behaviour. The activation of pro-inflammatory signalling pathways linked to obesity can result in vascular endothelial dysfunction and changed levels of Nitric oxide (NO). Hyperlipidaemia may exacerbate arterial stiffness which is a precursor to atherosclerosis. In this study, we tried to evaluate the changes in levels of nitric oxide in obese individuals and its association with arterial stiffness. Objectives: To identify the association of serum levels of Nitric oxide metabolites with Body Mass Index (BMI) in apparently healthy subjects. To evaluate any correlation between serum nitric oxide metabolites, BMI and arterial stiffness in obese individuals. Result: The results showed a significant increase in systolic blood pressure (p&lt;0.001) and no change in diastolic blood pressure and significant increase in pulse pressure(p&lt;0.001) with increase in visceral adiposity (Waist Circumference) more than BMI. Results of Pearson correlation indicated that there is a significant small negative relationship between BMI and Serum NO levels, (r =- 0.534, p &lt;.001). There was significant increase in Brachial ankle Pulse Wave Velocity (Ba PWV) (p=0.001) and Carotid Femoral Pulse Wave Velocity (CF PWV) (p=0.01) in obese subjects when compared to controls. Conclusion: Our study results showed that abdominal obesity more than overall obesity is more strongly associated with decreased serum NO levels and increased arterial stiffness. In obese individuals, increased arterial stiffness as reflected by increased pulse wave velocity may contribute to predicting cardiovascular disease in both genders in addition to development of hypertension.

Visceral Adiposity Index as an Indicator for Menstrual Disturbance, Hormonal and Metabolic Dysfunction in Polycystic Ovarian Syndrome.

Increase in visceral adiposity is characteristic of polycystic ovarian syndrome (PCOS) and is the main cause of insulin resistance and hyperandrogenism. This study tried to compare the visceral adiposity index (VAI) in PCOS women and control population, thereby exploring its correlation with ovarian morphology, hormonal and metabolic dysfunction. Reproductive-age women who fulfilled the Rotterdam criteria for PCOS constituted the cases. Control population consisted of the same number of non-PCOS women. History of menstrual irregularity and features of hyperandrogenism were noted. Overnight fasting serum hormonal profile on second day of the cycle, oral glucose tolerance test (OGTT) and serum fasting insulin and lipid profile were obtained. Ultrasound evaluation was done simultaneously. Free androgen index (FAI), homeostatic model assessment of insulin resistance (HOMA-IR) and VAI were calculated. Serum androgen levels and OGTT were greater in PCOS women. No significant difference was noted in serum fasting glucose, fasting insulin and lipid profile between cases and controls. Both systolic and diastolic blood pressures were significantly higher among women with PCOS. Mean ovarian volume, antral follicle count, FAI and HOMA-IR were higher in PCOS women. VAI was significantly higher in cases compared to controls. VAI demonstrated a strong negative correlation with number of menstrual cycles per year. Increasing VAI was associated with longer menstrual cycles and correlated positively with greater severity of anovulation. VAI also showed highly significant correlation with fasting blood glucose and statistically significant moderately strong positive correlation with OGTT values at two hours post glucose challenge, systolic blood pressure and mean ovarian volume.There was no demonstrable correlation between androgen levels or HOMA-IR values. VAI is higher in women with PCOS. It correlates positively with features of disease severity and ovarian morphology. An assessment of VAI in PCOS women could be predictive of a greater propensity for development of classical metabolic risk factors.

Dynapenic-abdominal obesity as an independent risk factor for chronic kidney disease in postmenopausal women: a population-based cohort study.

Low muscle strength and obesity lead to a higher risk of chronic kidney disease (CKD). Perimenopause is associated with a natural decline in muscle strength and an increase in visceral adiposity. Dynapenic obesity, which is the coexistence of low muscle strength and obesity, is expected to synergistically increase the prevalence of CKD in postmenopausal women. The aim of this study was to determine combined associations of dynapenia and obesity with CKD in postmenopausal women. This study used data from the Korean National Health and Nutrition Examination Survey, 2016 to 2019. The study included 4,525 postmenopausal women aged 42 to 80 years that were classified into four groups based on waist circumference (≥85 cm) and hand grip strength (<18 kg): normal, dynapenic, obese, or dynapenic-obese. According to the Kidney Disease: Improving Global Outcomes, we defined CKD as an estimated glomerular filtration rate <60 mL/min per 1.73 m2. Complex sample logistic regression models were conducted to determine the relationships among coexistence of dynapenia, abdominal obesity, and the risk of CKD. Dynapenic-abdominal obese group displayed lower estimated glomerular filtration rate levels than other groups (P < 0.05 for all data). The prevalence rates of CKD were 15.5%, 7.8%, 6.2%, and 2.4% in the dynapenic-abdominal obese, dynapenic, abdominal obese, and normal groups, respectively (P < 0.001). Complex sample logistic regression analyses, after adjusting for age, height, health behaviors, and comorbidities, showed that the odds ratio for CKD with respect to dynapenic-abdominal obesity was 1.82 (95% confidence interval, 1.19-2.79) and to abdominal obesity was 1.54 (95% confidence interval, 1.07-2.22) than in the normal group. This study demonstrated that dynapenic-abdominal obesity, as determined by low handgrip strength and high waist circumference values, was associated with increased risk of CKD in postmenopausal women.

Coronary microvascular function and visceral adiposity in patients with normal body weight and type 2 diabetes.

ObjectiveThis study sought to assess whether diabetes affects coronary microvascular function in individuals with normal body weight.MethodsSeventy‐five participants (30 patients with type 2 diabetes [T2D] who were overweight [O‐T2D], 15 patients with T2D who were lean [LnT2D], 15 healthy volunteers who were lean [LnHV], and 15 healthy volunteers who were overweight [O‐HV]) without established cardiovascular disease were recruited. Participants underwent magnetic resonance imaging for assessment of subcutaneous, epicardial, and visceral adipose tissue areas, adenosine stress myocardial blood flow (MBF), and cardiac structure and function.ResultsStress MBF was reduced only in the O‐T2D group (mean [SD], LnHV = 2.07 [0.47] mL/g/min, O‐HV = 2.08 [0.42] mL/g/min, LnT2D = 2.16 [0.36] mL/g/min, O‐T2D = 1.60 [0.28] mL/g/min; p ≤ 0.0001). Accumulation of visceral fat was evident in the LnT2D group at similar levels to the O‐HV group (LnHV = 127 [53] cm2, O‐HV = 181 [60] cm2, LnT2D = 182 [99] cm2, O‐T2D = 288 [72] cm2; p < 0.0001). Only the O‐T2D group showed reductions in left ventricular ejection fraction (LnHV = 63% [4%], O‐HV = 63% [4%], LnT2D = 60% [5%], O‐T2D = 58% [6%]; p = 0.0008) and global longitudinal strain (LnHV = −15.1% [3.1%], O‐HV= −15.2% [3.7%], LnT2D = −13.4% [2.7%], O‐T2D = −11.1% [2.8%]; p = 0.002) compared with both control groups.ConclusionsPatients with T2D and normal body weight do not show alterations in global stress MBF, but they do show significant increases in visceral adiposity. Patients with T2D who were overweight and had no prior cardiovascular disease showed an increase in visceral adiposity and significant reductions in stress MBF.

Evidence and consensus-based clinical practice guidelines for management of overweight and obesity in midlife women: An AIIMS-DST initiative.

Evidence and consensus-based clinical practice guidelines for management of overweight and obesity in midlife women: An AIIMS-DST initiative.

Sarcopenia and Appendicular Muscle Mass as Predictors of Impaired Fasting Glucose/Type 2 Diabetes in Elderly Women.

Elderly women exhibit a high risk of type 2 diabetes (T2D), but no definitive data exist about the possible role of postmenopausal increases in visceral adiposity, the loss of lean body mass, or decreases in the sum of the lean mass of arms and legs (appendicular skeletal muscle mass (ASMM)). This retrospective, longitudinal study investigated whether body composition (bioelectrical impedance analysis) predicted the development of impaired fasting glucose (IFG) or T2D in a cohort of 159 elderly women (age: 71 ± 5 years, follow-up: 94 months) from southern Italy (Clinical Nutrition and Geriatric Units of the “Mater Domini” University Hospital in Catanzaro, Calabria region, and the “P. Giaccone ”University Hospital in Palermo, Sicily region). Sarcopenia was defined in a subgroup of 128 women according to the EWGSOP criteria as the presence of low muscle strength (handgrip strength <16 kg) plus low muscle mass (reported as appendicular skeletal muscle mass <15 kg). Participants with a low ASMM had a higher IFG/T2D incidence than those with a normal ASMM (17% vs. 6%, p-adjusted = 0.044); this finding was independent of BMI, fat mass, waist circumference, and habitual fat intake (OR = 3.81, p = 0.034). A higher incidence of IFG/T2D was observed in the subgroup with sarcopenia than those without sarcopenia (33% vs. 7%, p-adjusted = 0.005) independent of BMI and fat mass (OR = 6.75, p = 0.007). In conclusion, this study demonstrates that elderly women with low ASMM had a higher probability of developing IFG/T2D. Further studies are needed to confirm these results in men and in other age groups.

High-Carbohydrate Diet Enhanced the Anticontractile Effect of Perivascular Adipose Tissue Through Activation of Renin-Angiotensin System

The perivascular adipose tissue (PVAT) is an active endocrine organ responsible for release several substances that influence on vascular tone. Increasing evidence suggest that hyperactivation of the local renin-angiotensin system (RAS) in the PVAT plays a pivotal role in the pathogenesis of cardiometabolic diseases. However, the local RAS contribution to the PVAT control of vascular tone during obesity is still not clear. Since the consumption of a high-carbohydrate diet (HC diet) contributes to obesity inducing a rapid and sustained increase in adiposity, so that the functional activity of PVAT could be modulated, we aimed to evaluate the effect of HC diet on the PVAT control of vascular tone and verify the involvement of RAS in this effect. For that, male Balb/c mice were fed standard or HC diet for 4 weeks. Vascular reactivity, histology, fluorescence, and immunofluorescence analysis were performed in intact thoracic aorta in the presence or absence of PVAT. The results showed that HC diet caused an increase in visceral adiposity and also in the PVAT area. Phenylephrine-induced vasoconstriction was significantly reduced in the HC group only in the presence of PVAT. The anticontractile effect of PVAT induced by HC diet was lost when aortic rings were previously incubated with angiotensin-converting enzyme inhibitor, Mas, and AT2 receptors antagonists, PI3K, nNOS, and iNOS inhibitors, hydrogen peroxide (H2O2) decomposing enzyme or non-selective potassium channels blocker. Immunofluorescence assays showed that both Mas and AT2 receptors as well as nNOS and iNOS isoforms were markedly expressed in the PVAT of the HC group. Furthermore, the PVAT from HC group also exhibited higher nitric oxide (NO) and hydrogen peroxide bioavailability. Taken together, these findings suggest that the anticontractile effect of PVAT induced by HC diet involves the signaling cascade triggered by the renin-angiotensin system through the activation of Mas and AT2 receptors, PI3K, nNOS, and iNOS, leading to increased production of nitric oxide and hydrogen peroxide, and subsequently opening of potassium channels. The contribution of PVAT during HC diet-induced obesity could be a compensatory adaptive characteristic in order to preserve the vascular function.

Cannabinoid receptors are differentially regulated in the pancreatic islets during the early development of metabolic syndrome

ABSTRACT The endocannabinoid system is found in tissues that regulate the glycemia, including adipose tissue, muscle, and pancreatic islets. Diet-induced metabolic syndrome changes the expression of the CB receptors in muscle, adipose tissue, and liver. However, it is poorly understood whether metabolic syndrome (MetS) affects the expression of CB receptors in pancreatic β cells. We analyzed the expression of CB receptors in pancreatic β cells under chronic high-sucrose diet (HSD)-induced MetS. Wistar rats fed an HSD as a model of MetS were used to investigate changes in cannabinoid receptors. After 8 weeks of treatment, we evaluated the appearance of the following MetS biomarkers: glucose intolerance, hyperinsulinemia, insulin resistance, hypertriglyceridemia, and an increase in visceral adiposity. To determine the presence of CB1 and CB2 receptors in pancreatic β cells, immunofluorescence of primary cell cultures and pancreatic sections was performed. For whole-islet quantification of membrane-bound CB1 and CB2 receptors, western-blotting following differential centrifugation was conducted. Our results revealed that an HSD treatment closely mimics the alterations seen in MetS. We observed that in primary cell culture, CB1 and CB2 receptors were expressed at a higher level in pancreatic β cells compared with non-β cells. MetS resulted in a reduction of CB1 in the islet, whereas abundant CB2 was observed after the treatment. CB1 and CB2 receptors are differentially expressed in pancreatic β cells during MetS development.

Cardiovascular Risks of Androgen Deprivation Therapy for Prostate Cancer.

Androgen deprivation therapy (ADT) is the gold standard treatment in patients with locally advanced or metastatic prostate cancer (PC). Emerging evidence has documented a tight association between ADT and body composition, along with metabolic profile impairment. These alterations might underpin the observed ADT-related increase in cardiovascular (CV) and thromboembolic (venous thromboembolism, VTE) mortality and morbidity. However, the specific mechanisms underlying these associations have not yet been completely elucidated. In the present review we summarize and discussed the available evidence linking ADT to increased cardio-metabolic risk, using both preclinical and clinical data. When possible, meta-analytic studies were preferred. Preclinical evidence, using a rabbit model of gonadotrophin-releasing hormone analogue-induced hypogonadism, indicates that the induced condition is associated with a dramatic increase in visceral adiposity and with an impairment of acetylcholine induced vascular relaxation, along with an increased propensity towards fatty liver. This suggests a direct role of ADT in inducing a worsened metabolic profile. In contrast, available clinical data are not sufficient to clarify a direct pathogeniclink between reduced testosterone (T) and altered metabolism. In fact, although T deprivation is associated with an altered metabolism, it is possible that the association between ADT and CV or VTE risk could simply be the result of a selection bias, related to the poor health status of patients with advanced PC. Despite the aforementioned considerations, all patients who are candidatesfor ADT should be screened for CV risk factors at baseline and monitored during the therapy. Life-style modifications and physical exercise are strongly encouraged.

Dexras1 plays a pivotal role in maintaining the equilibrium between adipogenesis and osteogenesis

BackgroundChronic steroid treatment causes an increase in visceral adiposity and osteoporosis. It is believed that steroids may alter a balance between differentiation of mesenchymal stem cells (MSCs) into either adipocytes or osteoblasts; however, the detailed molecular mechanisms are unclear. We previously identified Dexras1 as a critical factor that potentiates adipogenesis in response to glucocorticoids. Thus, in this study, we investigated the role of Dexras1 in maintaining the balance between chronic steroid treatment-associated adipogenesis and osteoporosis. Material and methodsWe treated wild type (WT) and Dexras1 knockout (KO) mice with dexamethasone for five weeks followed by 60% HFD for additional two weeks with dexamethasone. The changes of glucocorticoid-induced body weight gain and osteoporosis were analyzed. Bone marrow derived stromal cells (BMSCs) and mouse embryonic fibroblasts (MEFs) extracted from WT and Dexras1 KO mice, as well as MC3T3-E1 pre-osteoblasts and osteoclasts differentiated from RAW264.7 were analyzed to further define the role of Dexras1 in osteoblasts and osteoclasts. ResultsDual-energy X-ray absorptiometry and micro-computed tomography analyses in murine femurs revealed that Dexras1 deficiency was associated with increased osteogenesis, concurrent with reduced adipogenesis. Furthermore, Dexras1 deficiency promoted osteogenesis of BMSCs and MEFs in vitro, suggesting that Dexras1 deficiency prevents steroid-induced osteoporosis. We also observed that Dexras1 downregulated SMAD signaling pathways, which reduced the osteogenic differentiation capacity of pre-osteoblast MC3T3-E1 cells into mature osteoblasts. ConclusionWe propose that Dexras1 is critical for maintaining the equilibrium between adipogenesis and osteogenesis upon steroid treatment.

Relationship between visceral adiposity index and male infertility.

The visceral adiposity index (VAI), which is calculated by using parameters such as body mass index (BMI), waist circumference, triglyceride, and high-density lipoprotein cholesterol, has been reported to be associated with visceral fat distribution and increased cardiometabolic risk. We aimed to investigate the relationship between the VAI and hormone profiles as well as semen analysis in male infertility. This retrospective study included 278 adult men that were admitted to the urology and endocrine outpatient clinics. Patient data were reviewed, and outcomes were recorded. BMI and VAI were calculated and noted separately. BMI was negatively correlated with serum testosterone and testosterone/ estradiol ratio (T/E2) (p<.05 for all). There was no significant relationship between BMI and semen parameters (p>.05 for all). However, there was a significant negative correlation between VAI and semen parameters, total serum testosterone and T/E2 (p<.05 for all). Furthermore, VAI was independently associated with the total motility score. The increase in visceral adiposity that can be demonstrated by VAI may adversely affect male fertility due to its metabolic and hormonal effects. Since infertility occurs as a result of different metabolic conditions, the underlying mechanisms can be better understood from a multidisciplinary perspective.

Malt Extract as a Healthy Substitute for Refined Sugar

An overconsumption of refined added sugars may cause inflammation, insulin resistance and an increase in visceral adiposity. It is important to highlight that refined sugar is devoid of micronutrients and phytochemicals and natural sweeteners such as malt extract and honey have a different effect in oxidative stress markers and overall health. Malt extract contains approximately 90% carbohydrate, most of it in the form of maltose, B vitamins (mainly niacin), amino acids and some minerals such as magnesium and potassium. It is also rich in phenolic compounds mainly ferulic acid and flavan-3-ols. It has a high antioxidant activity, both in vitro and in vivo, which makes malt extract a healthy substitute for refined sugars.

Change in CT-measured abdominal subcutaneous and visceral but not thigh fat areas predict future insulin sensitivity

AimsWe examined the longitudinal association between change in body composition directly measured by computed tomography (CT) and future insulin sensitivity. MethodsThis was a prospective study with 10 years of follow-up with 297 Japanese-American without diabetes. Intra-abdominal fat area (IAFA) and abdominal subcutaneous fat area (SCFA), and thigh SCFA were measured by CT. Insulin sensitivity was calculated by HOMA-IR and the Matsuda index. ResultsBaseline and change in IAFA were significantly and independently associated with change in HOMA-IR and Matsuda index during follow-up. In multivariate analysis, IAFA and 10-year change in IAFA (Δ IAFA) was significantly and positively associated with 10-year HOMA-IR (p < 0.001) and significantly and negatively associated with 10-year Matsuda index (p < 0.001). The association with Matsuda index though was non-linear and best modeled as a quadratic function (Δ IAFA + Δ IAFA2). No significant associations in multivariate analyses were seen between thigh SCFA and insulin sensitivity or abdominal SCFA and HOMA-IR but an increase in abdominal SCFA was associated with diminished insulin sensitivity measured by the Matsuda index. ConclusionsAn increase in visceral adiposity predicts diminished insulin sensitivity over 10 years of follow-up independent of the size of this adipose depot at baseline.

MON-098 FSH and Body Composition in Older Adults

Background: Common changes with menopause and aging include an increase in visceral adiposity and loss of lean body mass. Declines in sex steroid hormones contribute to these body composition changes, but emerging evidence also implicates increased pituitary production of follicle stimulating hormone (FSH). Blocking FSH action with an FSH-β subunit antibody reduced adiposity and increased lean body mass in ovariectomized female mice, and both male and female intact mice (Liu Nature 2017). Some, but not all, clinical observational studies have demonstrated positive associations between FSH and measures of adiposity (Zaidi Endocrinology 2018). Objective: To investigate the associations between endogenous FSH levels and measures of body composition in older adults from the AGES-Reykjavik cohort, independent of sex steroid hormones. Methods/Results: Participants were recruited from the AGES-R study, excluding those using sex steroid hormone agonists or antagonists. FSH (ELISA), total estradiol and total testosterone (GC/MS) were measured from fasting serum. Total body fat (kg), total body lean mass (kg), and appendicular lean mass (kg) were measured with total body DXA. Appendicular lean mass index (ALMI) was calculated as appendicular lean mass/height2 (kg/m2). Visceral adipose tissue (VAT) area (cm2) and subcutaneous adipose tissue (SAT) area (cm2) were measured with abdominal CT. Linear regression analyses of FSH in association with body composition parameters were performed, stratified by gender, both unadjusted and adjusted for age, visit window, BMI, total estradiol and total testosterone levels. Among the 245 men, the mean age was 82.4 (SD 4.0) years, mean BMI was 26.7 (SD 3.6) kg/m2 and mean FSH 19.0 (SD 16.9) IU/L . Among the 238 women, the mean age was 80.6 (SD 4.0) years, mean BMI 27.4 (SD 4.1) kg/m2 and mean FSH 71.6 (SD 23.2) IU/L. In models adjusted for age, visit window, BMI, estradiol and testosterone, there were no significant associations between FSH and any measure of body composition in men. In adjusted models in women, each SD increase in FSH was associated with a 2.67% greater SAT area (p=0.03) but no significant difference in VAT area or total body fat. Conversely, each SD increase in FSH was associated with a1.62% lower total body lean mass (p=0.005) in women, but no significant difference in ALMI. Conclusion: Consistent with preclinical models, we found higher FSH to be associated with greater subcutaneous adiposity and lower lean body mass in older women. We found no associations between FSH and measures of body composition in older men. Further research is needed to determine whether FSH-directed therapy may be an effective means of combatting the body composition changes associated with menopause.

Neonatal tobacco smoke reduces thermogenesis capacity in brown adipose tissue in adult rats.

Maternal smoking is a risk factor for progeny obesity. We have previously shown, in a rat model of neonatal tobacco smoke exposure, a mild increase in food intake and a considerable increase in visceral adiposity in the adult offspring. Males also had secondary hyperthyroidism, while females had only higher T4. Since brown adipose tissue (BAT) hypofunction is related to obesity, here we tested the hypothesis that higher levels of thyroid hormones are not functional in BAT, suggesting a lower metabolic rate. We evaluated autonomic nerve activity in BAT and its function in adult rats that were exposed to tobacco smoke during lactation. At birth, litters were adjusted to 3 male and 3 female pups/litter. From postnatal day (PND) 3 to 21, Wistar lactating rats and their pups were divided into SE group, smoke-exposed in a cigarette smoking machine (4 times/day) and C group, exposed to filtered air. Offspring were sacrificed at PND180. Adult SE rats of both genders had lower interscapular BAT autonomic nervous system activity, with higher BAT mass but no change in morphology. BAT UCP1 and CPT1a protein levels were decreased in the SE groups of both genders. Male SE rats had lower β3-AR, TRα1, and TRβ1 expression while females showed lower PGC1α expression. BAT Dio2 mRNA and hypothalamic POMC and MC4R levels were similar between groups. Hypothalamic pAMPK level was higher in SE males and lower in SE females. Thus, neonatal cigarette smoke exposure induces lower BAT thermogenic capacity, which can be obesogenic at adulthood.