Intra-abdominal Adipose Tissue Accumulation Research Articles

A5 A MOUSE MODEL TO UNRAVEL THE PATHOPHYSIOLOGICAL LINK BETWEEN CROHN’S DISEASE AND TYPE-2 DIABETES-ASSOCIATED METABOLIC DISORDERS

Abstract Background Crohn’s disease (CD), an idiopathic inflammatory bowel disease (IBD), has been recently shown to increase the risk of developing type 2 diabetes (T2D). Moreover, treatment with anti-diabetic drugs has a protective role in preventing the severity and course of CD progression. However, the pathophysiological basis of T2D development in CD remains unclear. Findings have highlighted the contribution of adipose tissue (AT) to the development of chronic inflammatory diseases and have identified parallels between T2D and CD that may provide hints to common mechanisms of disease pathogenesis. Typically, microbial dysbiosis, hyperpermeable intestinal barrier, and intra-abdominal AT accumulation are the common features of both diseases, yet how the interplay of these factors contribute to pathogenesis is not known. Therefore, common pathogenic paradigms underlying both T2D and CD have led us to hypothesize that chronic intestinal inflammation serves as an initiator of AT dysfunction in CD, predisposing individuals to T2D. Further, the lack of appropriate animal models of CD with chronic intestinal inflammation that manifests accumulation of intra-abdominal AT, and extra-intestinal metabolic disorder as observed in CD and T2D patients has been a limitation. Purpose To develop a genetic mouse model to investigate if gut inflammation-mediated microbial dysbiosis and metabolic dysregulation of AT are at the nexus that cause T2D in CD. Method We developed a CD-mouse model, where we challenged Nod2-deficient mice (NOD2 being the strongest genetic risk factor contributing to CD) with a chronic inflammatory insult regime, using dextran sulfate sodium (cDSS) for 3 cycles. Subsequently, intraperitoneal insulin and oral glucose tolerance tests, metabolic caging, and MRI imaging of mice were performed. Changes in AT metabolism and microbial infiltration into AT were analyzed by quantitative real-time PCR (qRT-PCR) and/or immunohistochemistry (IHC). Result(s) Our new CD-mouse model revealed increased gut inflammation (TNF and type-I IFN) in Nod2-deficient mice compared to wild-type control mice post-cDSS. Surprisingly, Nod2-deficient mice gained body weight, which was at least in part accounted for by an increased intra-abdominal AT accumulation along with decreased AT fatty-acid metabolism (Cpt1a, Fabp4 expression) and AT browning (Ucp1, Cidea expression, and UCP-1 staining), reduced intestinal goblet cell numbers, increased gut bacterial infiltration within the fat, more insulin resistance and energy expenditure. Conclusion(s) This experimental mouse model mimicking CD-associated T2D will provide insights into how the microbiome-AT axis fuel chronic inflammation-mediated extra-intestinal metabolic disorder and immune dysregulation. Understanding these connections will be transformative, as it will help us devise novel therapeutic strategies to prevent T2D development in progressive CD patients. Disclosure of Interest None Declared

The Association between Visceral Fat, Dietary Patterns, and Comorbidities

Visceral fat is technically the excess accumulation of intra-abdominal adipose tissue. This type of fat is stored further underneath the skin than subcutaneous fat and it’s actually wrapped around major organs, including liver, pancreas and kidneys. Studies have shown that visceral fat plays a distinctive and potentially dangerous role affecting hormones function and it is also associated with increased risks of a number of health problems. Many indicators have been used to link visceral fats to chronic diseases including diabetes type 2, CVD, and arthritis. Anthropometric measurements, such as BMI, skinfold thickness, fat percentage, Waist Circumference, Hip Circumference and Waist/Hip Ratio indicating abdominal obesity. Dietary patterns also play a major role in overweight and obesity and in the amount of visceral fat accumulated in the body. The aim of the study was to find the association between visceral fat and chronic disease and also to identify the link between dietary patterns and chronic diseases. 61 males and 67 females participated in this study. Their anthropometric measurements were recorded together with their lipid profile and their energy intake and the number of servings of fruits, vegetables and dairy were also registered. The results have shown that females had higher BMI, waist and hip circumference, values of LDL, TG, TC and HDL than males and difference was statistically significant (p < 0.05). Waist/Hip ratio was higher in females but skinfold thickness was higher in males. Energy intake was almost similar in males (2800 kcal) and females (2700 kcal) but females consumed more calories from CHO and fewer calories from protein and fat. They also consumed less fruits and dairy products. However, they consumed similar number of servings of vegetables. More females were diagnosed with chronic diseases such as diabetes, CVD, hypertension and arthritis comparing to their males counterpart.

The Relation of Intra-Abdominal Adipose Tissue Accumulation and the Development of Vulnerable Carotid Atherosclerotic Plaques in Diabetes Mellitus.

Objective: The aim of study was determining the relation between the quality of metabolic control, anthropometric parameters and ultrasound measurement of fat accumulation and carotid atherosclerotic plaques vulnerability in patients with type 2 diabetes. Methods: The study included 51 patients with type 2 diabetes mellitus and 50 healthy individuals. The assessment of plaque vulnerability relies on quantitative and qualitative plaque ultrasound analysis. The thickness of intraabdominal adipose tissue was measured as a distance between the frontal wall of abdominal aorta and the dorsal wall of rectus abdominis muscles; the measurements are performed by placing transducer 5 cm above the umbilicus. Results: Atherosclerotic plaque was found in all of diabetic patients, comparing to 28.12% in the control group; among those, 47.06% with diabetes and 25.6% of control patients had vulnerable plaque. The vulnerability of atherosclerotic plaque was significantly related to age, duration of diabetes, glycaemia, waist circumference, waist / hip ratio, intra-abdominal adipose tissue thickness, intra-abdominal/subcutaneous fat ratio, dyslipidemia and hypertension. Conclusions: Carotid atherosclerotic plaques, particularly vulnerable ones, are far more prevalent in diabetic patients. Advanced age, poor glycemic control, obesity and the intra-abdominal fat accumulation contribute to carotid atherosclerotic plaques vulnerability. Despite the significant correlations with metabolic/anthropometric measurements, none of the predisposing factors could be identified as the independent risk factor; obviously, the increased vulnerability of has been the result of the synergistic effects of multiple pathogenic mechanisms. Moreover, ultrasound measurements of intra-abdominal fat did not show a decisive advantage over the classical anthropometric measurements in estimating atherosclerotic and metabolic risk.

Design of a lifestyle intervention to slow menopause-related progression of intra-abdominal adipose tissue in women: The Women in the Southside Health and Fitness (WISHFIT) study.

BackgroundChanges in reproductive hormones during menopause are associated with accumulation of intra-abdominal adipose tissue (IAAT), a subclinical indicator of cardiometabolic disease risk. Independent of reproductive hormones, unhealthy lifestyle contributes to IAAT gain. The Women in the Southside Health and Fitness (WISHFIT) Study aims to develop a lifestyle approach to slowing IAAT accumulation as women begin the menopausal transition.MethodsThe primary aim is to develop and conduct a proof-of-concept test of a multi-component, multi-level behavioral intervention targeting jointly physical activity, diet, and psychological well-being. Participants attend group sessions over 2 years to experiment with healthy living through both experiential and didactic learning, cultivate a health network, and draw on community resources to sustain change. The primary endpoint is 2-year IAAT progression, assessed using computerized tomography. Behavioral targets of treatment and secondary endpoints will be evaluated at 6, 12, 18 and 24 months. Change in social networks and community support will be assessed at 2 years.ResultsWISHFIT recruited 71 pre- and peri-menopausal Caucasian and African American women (mean ± SD age = 47.6 ± 3.4 yrs; BMI = 33.6 ± 7.3 kg/m2; 52% African American). Baseline IAAT was 2104.1 ± 1201.3 cm3. IAAT, physical activity, BMI, and self-reported family income and resilience differed by ethnicity at baseline.ConclusionsWISHFIT is a multi-component, multi-level intervention aimed at producing a sustained improvement in physical activity, diet, and psychological well-being early in the menopausal transition to slow menopause-related accumulation of IAAT. It provides a model for the process of developing a behavioral treatment to manage a chronic disease.

P-052: Accumulation of intra-abdominal adipose tissue in pediatric Crohn’s disease

P-051 Changes in selective lipids during treatment-induced remission of active pediatric IBD V. Brahmbhatt1 *, F.P. Martin2, N. Bosco1, I. Montoliu1, M. Oliveira1, P. Guy1, S. Schatz3, K. Werkstetter3, E. Schiffrin1, B. Koletzko3, J. Benyacoub1, S. Koletzko3. 1Nestle Research Center, Lausanne, Switzerland, 2Nestle Institute of Health Sciences, Lausanne, Switzerland, 3Dr. von Hauner Children’s Hospital, Munich, Germany

Pathophysiology of Human Visceral Obesity: An Update

Excess intra-abdominal adipose tissue accumulation, often termed visceral obesity, is part of a phenotype including dysfunctional subcutaneous adipose tissue expansion and ectopic triglyceride storage closely related to clustering cardiometabolic risk factors. Hypertriglyceridemia; increased free fatty acid availability; adipose tissue release of proinflammatory cytokines; liver insulin resistance and inflammation; increased liver VLDL synthesis and secretion; reduced clearance of triglyceride-rich lipoproteins; presence of small, dense LDL particles; and reduced HDL cholesterol levels are among the many metabolic alterations closely related to this condition. Age, gender, genetics, and ethnicity are broad etiological factors contributing to variation in visceral adipose tissue accumulation. Specific mechanisms responsible for proportionally increased visceral fat storage when facing positive energy balance and weight gain may involve sex hormones, local cortisol production in abdominal adipose tissues, endocannabinoids, growth hormone, and dietary fructose. Physiological characteristics of abdominal adipose tissues such as adipocyte size and number, lipolytic responsiveness, lipid storage capacity, and inflammatory cytokine production are significant correlates and even possible determinants of the increased cardiometabolic risk associated with visceral obesity. Thiazolidinediones, estrogen replacement in postmenopausal women, and testosterone replacement in androgen-deficient men have been shown to favorably modulate body fat distribution and cardiometabolic risk to various degrees. However, some of these therapies must now be considered in the context of their serious side effects. Lifestyle interventions leading to weight loss generally induce preferential mobilization of visceral fat. In clinical practice, measuring waist circumference in addition to the body mass index could be helpful for the identification and management of a subgroup of overweight or obese patients at high cardiometabolic risk.

Effects of Recombinant Growth Hormone on Visceral Fat Accumulation: Pilot Study in Human Immunodeficiency Virus-Infected Adolescents

Recombinant human GH (rhGH) reduces excess accumulation of intraabdominal adipose tissue (IAT) in lipodystrophic HIV-infected adults, whereas data in pediatric patients are lacking. The objective of this study was to assess the efficacy of rhGH treatment on lipodystrophy in HIV-infected adolescents. The study is a prospective, 24-wk open-label study of rhGH. The study was conducted at a referral center for pediatric HIV infection. Eight HIV-infected adolescents (ages, 13.7-18.5 yr), with abnormal IAT accumulation (>41 cm(2) at L4-magnetic resonance imaging) and 97 healthy controls (HC) (ages, 9.5-19.9 yr) were enrolled. rhGH was given by sc injection at a daily dose of 0.028 mg/kg. The main outcome was change in IAT at L4-magnetic resonance imaging. Body composition by dual-energy x-ray absorptiometry, glucose and lipid metabolism, and IGF-I changes were also evaluated. All patients completed the study period; none of them showed adverse event, and no change in the daily dose of rhGH was required. The treatment was associated with a mean height increase of 2.4 cm. From baseline to wk 24, IAT area decreased significantly by a median of 34.5% (-19.2 to -70%). Fat mass decreased significantly in patients, compared with HC, with a median loss of total, trunk, and arm and leg fat mass of 10.4, 10.9, 12.7, and 5.4%, respectively. Total, arm, and leg lean masses increased significantly, compared with HC. IGF-I increased significantly, but supraphysiological values of mild degree (2-23% over the upper normal limit) were detected in only nine of 24 samples. No significant effects on glucose metabolism, triglyceride, and cholesterol levels were observed. Our data showed that rhGH 0.028 mg/kg daily for 24 wk in HIV-infected adolescents reduces IAT, trunk, and also limb fat and increases lean mass. Overall, short-term rhGH is well tolerated and is not associated with a worsening of glucose and lipid metabolism.

Impaired growth hormone secretion correlates with visceral adiposity in highly active antiretroviral treated HIV-infected adolescents.

HIV-infected adults with lipodystrophy, characterized by excess accumulation of intra-abdominal adipose tissue (IAT), showed impaired growth hormone (GH) secretion. Data are lacking in paediatric lipodystrophy with the same features. Twenty-five pubertal HIV-infected children were assessed for GH response (GH-AUC(0-120 min)) to arginine + GHRH testing, insulin-like growth factor-1 (IGF-1), IGF binding protein 3 (IGFBP-3), insulin, glucose, cholesterol, triglycerides, free fatty acids and nitric oxide levels. Body composition and IAT content were evaluated by dual-energy x-ray-absorptiometry and magnetic resonance imaging. An excess accumulation of IAT was defined as a value > 41 cm2. Differences between children with (V+) and without (V-) excess IAT were assessed by non-parametric tests and multivariate analysis. RESULTS Ten V+ (mean IAT, 82.5 cm2) and 15 V- (mean IAT, 26.8 cm2) were identified; they were similar for age (13.8 versus 14.8 years), body mass index (20.2 versus 19.5 kg/m2), male : female ratio (3/7 versus 8/7), months on highly active antiretroviral therapy (54.5 versus 55 months). V+ showed lower GH-AUC(0-120 min) (16.4 versus 31.6 microg x h/l; P = 0.002), lower IGF-1 concentrations (384 versus 515 ng/ml; P = 0.03) and higher insulin levels (17.8 versus 10.5 microIU/ml; P = 0.01) than V-. V+, as compared to V-, showed lower lean mass (total, P = 0.025; arms, P = 0.024; legs, P = 0.008) and higher fat mass (total, P = 0.0038; arms, P = 0.028; trunk, P < 0.0001). Lipid profile and glucose, IGFBP-3, nitric oxide and free fatty acids levels were similar in the two groups. GH-AUC(0-120 min) correlated negatively with IAT content and insulin levels. Impaired GH secretion is detectable in pubertal children with increased visceral adiposity and hyperinsulinemia. GH therapy should be considered in lipodystrophic HIV-infected children with excess IAT.

Effects of the menopause transition on body fatness and body fat distribution.

The menopause transition increases cardiovascular and metabolic disease risk, partly because of the adverse effects of estrogen deficiency on the plasma lipid-lipoprotein profile and cardiovascular function. This increased cardiovascular and metabolic disease risk may also be partially mediated by increased body fat, increased intra-abdominal adipose tissue accumulation, or both. The objective of this mini-review is to summarize studies that have investigated the relationships among the menopause transition, body fatness, and body fat distribution. A review of cross-sectional and longitudinal studies on menopause that examined body fatness and body fat distribution. Cross-sectional reports show that the menopause transition is related to modest increases in body mass index or total fatness, although not all studies found significant effects. Increased central adiposity appears to be related to menopause, independent of advancing age, but these results are methodology dependent. An independent effect of menopause on central body fatness was noted by the use of techniques such as DEXA or computed tomography, whereas studies using circumference measures showed discrepant results. Longitudinal studies showed that the menopause transition accelerated the increase in central adiposity, although no studies quantified changes in intra-abdominal fat by imaging techniques. Thus, additional longitudinal studies using more accurate measures of adiposity are needed to critically examine the effects of the menopause transition on total and central body fatness. Collectively, previous studies suggest that menopause is related to modest increase in total fatness and accelerated accumulation of central body fat that exceeds changes normally attributed to the aging process. These changes may increase the risk for cardiovascular and metabolic disease in aging women.