Excess Visceral Adipose Tissue Research Articles

Milk protein for improved metabolic health: a review of the evidence

Epidemiological evidence shows that consumption of dairy products is associated with decreased prevalence of metabolic related disorders, whilst evidence from experimental studies points towards dairy protein as a dietary component which may aid prevention of type 2 diabetes (T2DM). Poor metabolic health is a common characteristic of overweight, obesity and aging, and is the forerunner of T2DM and cardiovascular disease (CVD), and an ever increasing global health issue. Progressive loss of metabolic control is evident from a blunting of carbohydrate, fat and protein metabolism, which is commonly manifested through decreased insulin sensitivity, inadequate glucose and lipid control, accompanied by a pro-inflammatory environment and hypertension. Adverse physiological changes such as excess visceral adipose tissue deposition and expansion, lipid overspill and infiltration into liver, muscle and other organs, and sarcopaenia or degenerative loss of skeletal muscle mass and function all underpin this adverse profile. ‘Sarcobesity’ and sarcopaenic diabetes are rapidly growing health issues. As well as through direct mechanisms, dairy protein may indirectly improve metabolic health by aiding loss of body weight and fat mass through enhanced satiety, whilst promoting skeletal muscle growth and function through anabolic effects of dairy protein-derived branch chain amino acids (BCAAs). BCAAs enhance muscle protein synthesis, lean body mass and skeletal muscle metabolic function. The composition and processing of dairy protein has an impact on digestion, absorption, BCAA kinetics and function, hence the optimisation of dairy protein composition through selection and combination of specific protein components in milk may provide a way to maximize benefits for metabolic health.

Visceral adiposity in gastrointestinal and hepatic carcinogenesis

There is emerging evidence that the association between obesity and cancer is mediated by visceral rather than generalised body fat. Visceral fat has been directly implicated in the risk and progression of several gastrointestinal cancers including colorectal, oesophageal, pancreatic and hepatocellular carcinomas. Excess visceral adipose tissue induces a state of chronic systemic inflammation and altered metabolic activity that promotes a pro-oncogenic environment. This review examines the evidence linking visceral fat in gastrointestinal and hepatic carcinogenesis and explores our current understanding of the mechanisms underlying this relationship.

Abstract 19411: Inter-Atrial Regional Adipose Burden in Relation To Metabolic Abnormalities as a Novel Clinical Marker for Left Atrial Remodeling in Preserved Ejection Fraction Heart Failure

Background: Excessive visceral adipose tissue, a marker of abnormal metabolic process, has recently been shown to exert effects on cardiac struture and function. However, data regarding regional fat burden on left atrial (LA) mechanics and contractile function in subjects with heart failure and preserved ejection fraction (HFpEF) remained elusive. Methods: Totally studied 48 heart failure patients with preserved left ventricular ejection fraction (HFpEF) from heart failure (HF) outpatient clinics. Another 58 hypertensives and 26 normal volunteers were recruited from health evaluation center at the same time of patients enrollment. Myocardial deformation imaging from all directions, cardiac twist and left atrial (LA) strain analyzed. Global epicardial (EAT), thoracic peri-aortic (TAT) adipose tissue and regional inter-atrial fat burden (IAF, in thickness) were quantified by multi-detector Computed Tomography (MDCT) (Sensation 16, Siemens Medical Solutions, Forchheim, Germany) off-line analysis (Aquarius 3D Workstation, TeraRecon, San Mateo, CA, USA). Metabolic risk scoring (MS) was calculated by NCEP ATP III score. Results: Compared to hypertensives and normal group, patients with HFpEF tended to have higher LV mass index and LA diameter though similar LVEF (all p<0.05) observed. In addition, EAT, TAT and IAF all correlated with MS (trend p<0.05), and were all significantly higher in HFpEF group (ANOVA p<0.05), which were accompanied by significantly reduced LV deformation from all three directions and cardiac twist as well as lower LA strain (all p<0.05). In a multivariate model adjusting for age, gender, body mass index, blood pressure, MS and LV mass, for each increased standard deviation of IAF were independently associated with reduced LA strain (ß coef: -0.35, p=0.018). Conclusions: Fat pad surrounding inter-atrial region in relation to metabolic abnormalities may influence left atrial mechanical function in terms of atrial deformation. Our data suggested that such excessive regional adipose burden may partly play a role in the pathogenesis of early stage heart failure.

Oxidative stress is associated with visceral adipose tissue and subclinical atherosclerosis in a healthy multi-ethnic population

Oxidative stress plays an important role in the development of atherosclerosis. Excess visceral adipose tissue (VAT) and increased carotid intima-media thickness (IMT) are risk factors for coronary artery disease. We tested the hypothesis that VAT and IMT were associated with systemic oxidative stress. Healthy men and women (n = 565) matched for ethnicity (Aboriginal, Chinese, European, and South Asian) were recruited. Plasma malondialdehyde, a biomarker of oxidative stress, was measured as thiobarbituric acid reactive substances (TBARS). VAT and IMT were determined by computerized tomography and ultrasound scans, respectively. Plasma TBARS levels correlated with VAT and total atheroma burden (sum of IMT area and plaque area) in the entire cohort. When stratified by ethnicity, plasma TBARS levels correlated with distinct body composition and arterial measures in different ethnic populations with more associations present amongst Chinese and Europeans relative to Aboriginals and South Asians. VAT was associated with plasma TBARS levels independent of age, sex, ethnicity, smoking, and body mass index. Plasma TBARS levels were associated with IMT, the presence of plaques, and total atheroma burden, independent of age, sex, ethnicity, smoking, body mass index, and VAT. The association with total atheroma burden remained significant even when adjusted for apolipoprotein B. Results from the present study indicate that oxidative stress is positively associated with VAT as well as diffuse and focal carotid atherosclerosis in apparently healthy men and women.

Visceral and Not Subcutaneous Abdominal Adiposity Reduction Drives the Benefits of a 1‐Year Lifestyle Modification Program

Excess visceral adipose tissue (VAT) is associated with an increased cardiometabolic risk. The study examined whether changes in cardiometabolic risk markers after a 1-year lifestyle intervention in viscerally obese men were associated with changes in VAT or with changes in subcutaneous abdominal adipose tissue (SAT). The relative contributions of changes in global adiposity vs. changes in cardiorespiratory fitness to changes in VAT were also quantified. One hundred and forty four men were selected on the basis of an increased waist circumference (≥ 90 cm) associated with dyslipidemia (triglycerides ≥ 1.69 and/or high-density lipoprotein (HDL)-cholesterol <1.03 mmol/l); 117 men completed the 1-year intervention which consisted in a healthy eating, physical activity/exercise program. Body weight, body composition, and fat distribution were assessed by anthropometry and dual-energy X-ray absorptiometry (DEXA)/computed tomography. Cardiorespiratory fitness, plasma adipokine/inflammatory markers, fasting lipoprotein-lipid profile, and oral glucose tolerance test (OGTT) were assessed. VAT volume decreased by 26%, cardiorespiratory fitness improved by 20% (P < 0.0001) after 1 year. Plasma adipokine/inflammatory markers, lipids/lipoproteins, and glucose homeostasis were improved. One-year changes in triglyceride (r = 0.29), apolipoprotein B (r = 0.21), 120-min OGTT-glucose (r = 0.27), and fasting insulin (r = 0.27) levels correlated with changes in VAT (all P < 0.05) after adjustment for changes in SAT. Using a multilinear regression model, VAT reduction was independently associated with SAT reduction and with improvement in cardiorespiratory fitness (R(2) = 0.58, P < 0.0001). Therefore, this healthy eating-physical activity/exercise program improved the cardiometabolic risk profile of viscerally obese men in relation to the reduction of VAT. Furthermore, the reduction in VAT was independently related to the reduction in global adiposity and to the improvement in cardiorespiratory fitness.

Abstract MP028: Physical Activity Relates to Lower Visceral Adiposity in Children and Adolescents

Introduction: Expansion of visceral adipose tissue (VAT) associates with adverse metabolic changes. While regular moderate-to-vigorous activity is associated with lower total body fat in children and adolescents, it is unknown how physical activity relates to other adiposity indices, including VAT. Hypothesis: We hypothesized that regular physical activity in children and adolescents associates with lower body fat, percent body fat, abdominal subcutaneous adipose tissue (SAT), and VAT. Methods: The sample included 393 boys and girls aged 5–18 years (45.6% White, 50.6% African American, and 3.8% Other). Body fat and percent body fat were measured by dual-energy x-ray absorptiometry. Abdominal SAT and VAT mass were measured by magnetic resonance imaging between the highest point of the liver and the lower pole of the right kidney (using 5 to 8 cross-sectional slices, 4.76 cm apart). Participants were categorized as being regularly active by self-report: moderate-to-vigorous physical activity of ≥ 60 minutes/day, ≥ 4 days/week. Those who were physically active fewer than 4 days/week were categorized as not regularly active. Results: In this sample of children and adolescents, 45.6% of participants were regularly active. One-way ANCOVAs adjusted for age and sex demonstrated that regularly active youth had significantly less body fat (p&lt;0.01) and lower percent body fat (p&lt;0.01) than those who were not regularly active. One-way ANCOVAs adjusted for age, gender, and body fat, revealed that regularly active children and adolescents had no difference in SAT but had significantly lower amounts of VAT (p&lt;0.05) when compared to those who were not regularly active. Conclusion: Engagement in moderate-to-vigorous physical activity for at least 60 minutes on four or more days of the week in children and adolescents was related to lower body fat, percent body fat and VAT, when compared to those youth who were less active. The promotion of regular physical activity has significant public health implications for body fat accumulation and for controlling excess VAT during childhood and adolescence.

Physical Fitness and Fatness in Adolescents with Intellectual Disabilities

This study investigated health-related fitness in adolescents with intellectual disabilities and analysed the various performances in physical fitness tests according to degrees of obesity. Eighty-seven French intellectual disabilities adolescents (14.24 ± 1.48 years) performed the EUROFIT physical fitness test battery. Height, weight and waist circumference were assessed, and BMI and waist-to-height ratio were calculated. 'Bio-impedancemetry' evaluated body fat (BF) percentage. Ninety-four per cent of the adolescents completed the aerobic running test, 52% of which had low VO(2max). Thirty-seven per cent were obese (%BF), and 32% had excess visceral adipose tissue. Adolescents with the lowest cardiorespiratory fitness had the highest BF percentages (P < 0.001). Intellectual disabilities adolescents showed low physical fitness and high prevalence of obesity. Both could further worsen social participation and health status.

Omental Adipose Tissue–Derived Stromal Cells Promote Vascularization and Growth of Endometrial Tumors

Adipose tissue contains a population of tumor-tropic mesenchymal progenitors, termed adipose stromal cells (ASC), which engraft in neighboring tumors to form supportive tumor stroma. We hypothesized that intra-abdominal visceral adipose tissue may contain a uniquely tumor-promoting population of ASC to account for the relationship between excess visceral adipose tissue and mortality of intra-abdominal cancers. To investigate this, we isolated and characterized ASC from intra-abdominal omental adipose tissue (O-ASC) and characterized their effects on endometrial cancer progression as compared with subcutaneous adipose-derived mesenchymal stromal cells (SC-ASC), bone marrow-derived mesenchymal stromal cells (BM-MSC), and lung fibroblasts. To model chronic recruitment of ASC by tumors, cells were injected metronomically into mice bearing Hec1a xenografts. O-ASC expressed cell surface markers characteristic of BM-MSC and differentiated into mesenchymal lineages. Coculture with O-ASC increased endometrial cancer cell proliferation in vitro. Tumor tropism of O-ASC and SC-ASC for human Hec1a endometrial tumor xenografts was comparable, but O-ASC more potently promoted tumor growth. Compared with tumors in SC-ASC-injected mice, tumors in O-ASC-injected mice contained higher numbers of large tortuous desmin-positive blood vessels, which correlated with decreased central tumor necrosis and increased tumor cell proliferation. O-ASC exhibited enhanced motility as compared with SC-ASC in response to Hec1a-secreted factors. Visceral adipose tissue contains a population of multipotent MSCs that promote endometrial tumor growth more potently than MSCs from subcutaneous adipose tissue. We propose that O-ASCs recruited to tumors express specific factors that enhance tumor vascularization, promoting survival and proliferation of tumor cells.

Visceral obesity, metabolic syndrome, insulin resistance and cancer

This paper presents emerging evidence linking visceral adiposity and the metabolic syndrome (MetSyn) with carcinogenesis. The link between obesity and cancer has been clearly identified in a multitude of robust epidemiological studies. Research is now focusing on the role of visceral adipose tissue in carcinogenesis; as it is recognised as an important metabolic tissue that secretes factors that systemically alter the immunological, metabolic and endocrine milieu. Excess visceral adipose tissue gives rise to a state of chronic systemic inflammation with associated insulin resistance and dysmetabolism, collectively known as the MetSyn. Prospective cohort studies have shown associations between visceral adiposity, the MetSyn and increased risk of breast cancer, colorectal cancer and oesophageal adenocarcinoma. Furthermore, visceral adiposity and the MetSyn have been associated with increased tumour progression and reduced survival. The mechanisms by which visceral adiposity and the MetSyn are thought to promote tumorigenesis are manifold. These include alterations in adipokine secretion and cell signalling pathways. In addition, hyperinsulinaemia, subsequent insulin resistance and stimulation of the insulin-like growth factor-1 axis have all been linked with visceral adiposity and promote tumour progression. Furthermore, the abundance of inflammatory cells in visceral adipose tissue, including macrophages and T-cells, create systemic inflammation and a pro-tumorigenic environment. It is clear from current research that excess visceral adiposity and associated dysmetabolism play a central role in the pathogenesis of certain cancer types. Further research is required to elucidate the exact mechanisms at play and identify potential targets for intervention.

Human Omental-derived Adipose Stem Cells Decrease Ovarian Tumor Radiosensitivity and Promote Ovarian Tumor Proliferation, Migration, and Growth

Adipose tissue retains a population of multipotent mesenchymal stromal cells (ASC) which exhibit tumor tropism, similar to bone marrow derived mesenchymal stem cells (MSC). Excess visceral adipose tissue increases the risk of ovarian cancer and the omentum is a frequent site of ovarian cancer metastasis. We hypothesize omentum is a source of ASC which form stroma in ovarian cancers and promote tumor progression and resistance to therapy.

Assessing Adiposity

The prevalence of obesity in the United States and the world has risen to epidemic/pandemic proportions. This increase has occurred despite great efforts by healthcare providers and consumers alike to improve the health-related behaviors of the population and a tremendous push from the scientific community to better understand the pathophysiology of obesity. This epidemic is all the more concerning given the clear association between excess adiposity and adverse health consequences such as cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). The risks associated with overweight/obesity are primarily related to the deposition of adipose tissue, which leads to excess adiposity or body fatness. Furthermore, weight loss, specifically loss of body fat, is associated with improvement in obesity-related comorbidities. Before weight loss interventions can be recommended, however, patients must be assessed for their adiposity-related risk. Unfortunately, healthcare providers and systems have not done a good job of assessing for excess adiposity even in its simplest form, such as measuring body mass index (BMI). It is for these reasons that we must emphasize the importance of assessing adiposity in clinical practices. Although it can be argued that the entire population should be targeted as an important public health issue with a goal of prevention of weight gain and obesity, there are currently so many “at risk” individuals that simple strategies to identify and treat those individuals are necessary. We must identify those individuals at highest risk of comorbidities in order to identify those who might benefit the most from aggressive weight management. This scientific statement will first briefly review the epidemiology of obesity and its related comorbidities, supporting the need for improved assessment of adiposity in daily clinical practice. This will be followed by a discussion of some of the challenges and issues associated with assessing adiposity and then by a review …

021 Contributions of cardiac and abdominal visceral adipose tissues to the variation in the cardiometabolic profile of young and healthy adults

The association of excess abdominal visceral adipose tissue (VAT) to an atherogenic/diabetogenic cardiometabolic risk profile is well documented. An association of intrathoracic adipose tissue (IAT) and its components (epicardial and pericardial adipose tissues, EAT and PAT) to cardiometabolic risk has also been suggested. We therefore examined the associations between VAT and IAT, and their relationships to the cardiometabolic blood profile in a sample of young and apparently healthy adults. Two hundred and ten young and apparently healthy subjects (no known risk factors or cardiovascular/metabolic disease, 50.5%male; age 26.8 ± 4.2years; BMI 23.5 ± 4.2kg/m2) underwent magnetic resonance imaging after voluntary recruitment in the community. We quantified abdominal subcutaneous adipose tissue (SAT), VAT, IAT, EAT and PAT volumes on T1-weighted 5mm thick axial slices centered on L4-L5 for abdominal adipose tissues and on the mitral valve for IAT, EAT and PAT. Plasma cardiometabolic risk profile was assessed for each subject (TG = 0.98 ± 0.65mmol/L; LDL-cholesterol (C) = 2.47 ± 0.79mmol/L; HDL-C = 1.56 ± 0.46mmol/L; TC/HDL-C = 3.07 ± 1.03; glucose = 4.58 ± 0.46mmol/L; adiponectin = 9.98 ± 4.17μg/mL; ApoB/ApoA1 = 0.51 ± 0.18). Compared to young women, young men had higher LDL-C (2.70 ± 0.08 vs. 2.23 ± 0.07mmol/L, P< 0.0001), TC/HDL-C (3.55 ± 0.11 vs. 2.58 ± 0.06, P< 0.0001), glucose (4.73 ± 0.04 vs. 4.43 ± 0.04mmol/L, P< 0.0001), and ApoB/ApoA1 (0.59 ± 0.19 vs. 0.43 ± 0.14, P< 0.0001), but lower HDL-C (1.33 ± 0.03 vs. 1.80 ± 0.05mmol/L, P< 0.0001) and adiponectin (8.23 ± 0.31 vs. 11.75 ± 0.42μg/mL, P< 0.0001). Young men possessed more VAT (65.29 ± 3.84 vs. 41.09 ± 4.62.0mL/5mm, P = 0.0001) and IAT (12.20 ± 0.48 vs. 8.73 ± 0.32mL/5mm, P< 0.0001), but similar SAT (154.56 ± 8.16 vs. 161.42 ± 9.33mL/5mm, P = 0.6) compared to women. A strong association was observed between VAT and IAT (r = 0.68, P< 0.0001) (figure). High ApoB/ApoA1 and LDL-C levels were each associated with high VAT (P< 0.0001 for both ApoB/ApoA1 and LDL-C). We further noted that increasing IAT (in total and each of its components taken individually) was also associated with higher ApoB/ApoA1 and LDL-C (ApoB/ApoA1: P< 0.0001 for IAT, EAT and PAT; LDL-C = P = 0.0002 for IAT, P = 0.004 for EAT and P = 0.0008 for PAT). However, when adipose tissues compartments (SAT, VAT, EAT and PAT) were included in a multiple regression model, PAT and EAT were the only adipose tissues that remained independently associated with the ApoB/ApoA1 ratio (P= 0.03 and P< 0.0001, respectively), while PAT and VAT were the only adipose tissues independently associated with LDL-C (P= 0.03 and P = 0.04). In apparently healthy young adults, intrathoracic adipose tissue strongly correlates with abdominal visceral adiposity. Both intrathoracic and abdominal visceral adipose tissues are independently associated with the cardiometabolic risk profile of apparently healthy young adults.

Pro-inflammatory and tumour proliferative properties of excess visceral adipose tissue

Obesity has been associated with increased incidence and mortality of oesophageal and colorectal adenocarcinoma. Excess central adiposity may drive this association through an altered inflammatory milieu. Utilising a unique adipose tissue bioresource we aimed to determine the pro-tumour properties of visceral adipose tissue. Comparing subcutaneous and visceral adipose tissue depots, we observed significantly higher levels of VEGF and IL-6, along with significantly higher proportions of CD8 + T cells and NKT cells in visceral adipose tissue. Significantly higher levels of VEGF were observed in the conditioned media from visceral adipose tissue of centrally obese compared to non-obese patients. We also report a significant increase in oesophageal and colorectal tumour cell proliferation following culture with conditioned media from visceral adipose tissue of centrally obese patients. Neutralising VEGF in the conditioned media significantly decreased tumour cell proliferation. This novel report highlights a potential mechanism whereby visceral adipose tissue from centrally obese cancer patients may drive tumour progression.

Visceral adiposity, insulin resistance and cancer risk

BackgroundThere is a well established link between obesity and cancer. Emerging research is characterising this relationship further and delineating the specific role of excess visceral adiposity, as opposed to simple obesity, in promoting tumorigenesis. This review summarises the evidence from an epidemiological and pathophysiological perspective.MethodsRelevant medical literature was identified from searches of PubMed and references cited in appropriate articles identified. Selection of articles was based on peer review, journal and relevance.ResultsNumerous epidemiological studies consistently identify increased risk of developing carcinoma in the obese. Adipose tissue, particularly viscerally located fat, is metabolically active and exerts systemic endocrine effects. Putative pathophysiological mechanisms linking obesity and carcinogenesis include the paracrine effects of adipose tissue and systemic alterations associated with obesity. Systemic changes in the obese state include chronic inflammation and alterations in adipokines and sex steroids. Insulin and the insulin-like growth factor axis influence tumorigenesis and also have a complex relationship with adiposity. There is evidence to suggest that insulin and the IGF axis play an important role in mediating obesity associated malignancy.ConclusionsThere is much evidence to support a role for obesity in cancer progression, however further research is warranted to determine the specific effect of excess visceral adipose tissue on tumorigenesis. Investigation of the potential mechanisms underpinning the association, including the role of insulin and the IGF axis, will improve understanding of the obesity and cancer link and may uncover targets for intervention.

Effects of tesamorelin on inflammatory markers in HIV patients with excess abdominal fat: relationship with visceral adipose reduction

To report the effects of tesamorelin, a growth hormone-releasing hormone analogue, on inflammatory and fibrinolytic markers and to relate these effects to changes in visceral adipose tissue (VAT). Four hundred and ten HIV-infected patients with abdominal adiposity were randomized to 2 mg tesamorelin (n = 273) or placebo (n = 137) subcutaneously daily for 26 weeks. Circulating plasminogen activator inhibitor-1 (PAI-1) antigen, tissue plasminogen activator (tPA) antigen, C-reactive protein (CRP), and adiponectin were assessed. At baseline, VAT was significantly associated with PAI-1 antigen (ρ = 0.36, P < 0.001), tPA antigen (ρ = 0.29, P < 0.001), CRP (ρ = 0.18, P < 0.001), and adiponectin (ρ = -0.22, P < 0.001). Treatment with tesamorelin resulted in a significant decrease from baseline in tPA antigen (-2.2 ± 2.5 vs. -1.6 ± 2.9 ng/ml, tesamorelin vs. placebo, P < 0.05). Changes in PAI-1 antigen were not significant in the tesamorelin group compared to placebo. Among patients receiving tesamorelin, changes in inflammatory markers were associated with change in VAT (PAI-1 antigen: ρ = 0.16, P = 0.02; tPA antigen: ρ = 0.16, P = 0.02; adiponectin: ρ = -0.27, P < 0.001), and these associations remained significant when controlling for changes in insulin-like growth factor-1. In HIV patients with abdominal adiposity, tesamorelin may have a modest beneficial effect on adiponectin and fibrinolytic markers in association with changes in VAT. Further studies are needed to determine the clinical significance of these changes. These data further highlight the deleterious role of excessive VAT and the utility of strategies to improve VAT in this population.

Determination of the cutoff point for waist circumference that establishes the presence of abdominal obesity in Latin American men and women

AimsThe recent definitions of the metabolic syndrome (MS) recognize the need for ethnic and region-specific waist circumference (WC) cut-offs that identify people with abdominal obesity. We tested WC as a diagnostic tool to identify people with visceral adiposity in Hispanics from the Latin America region. MethodsWe used the area of visceral adipose tissue (VAT) ≥100cm2 at the level between the 4th and 5th lumbar vertebrae in abdominal CT scans as a marker of visceral adiposity and established the optimal WC threshold for men and women by means of receiver operating characteristic (ROC) curves. Results179 men and 278 women from Mexico, El Salvador, Venezuela, Colombia and Paraguay were included. The ROC curves were highly discriminative of excess VAT for men and women (area under the curve 0.9 and 0.8 respectively) and the WC threshold was identified at 94cm for men and between 90 and 92cm for women. ConclusionIn men the WC cutoff was equal to that proposed for europids and suggested for US adults who may have strong genetic contribution to insulin resistance such as Hispanics. In women the threshold was significantly higher than previously proposed for South and Central Americans.

Lipids in the Wrong Place: Visceral Fat and Nonalcoholic Steatohepatitis

There is substantial evidence in both animal (1,2) and human models of lipodystrophy (3) that the accumulation of excessive fat in ectopic sites that normally lack adipose tissue, such as the skeletal muscle and the liver, may trigger whole-body insulin resistance. This article will review the evidence showing the condition of fatty liver as an independent and perhaps better indicator of disease than excessive accumulation of visceral adipose tissue. On the basis of the hypothesis that a fatty liver may increase the risk of cardiovascular disease (CVD), this article will not only focus on the metabolic-related features, but also on the cardiovascular risk factors affecting individuals with fatty liver. The biomarkers of CVD will therefore be analyzed in patients with fatty livers. Finally, epidemiological evidence linking fatty liver to the development of type 2 diabetes and CVD will be given. ### Metabolic features of individuals with insulin impairment: what contributes more, fatty liver or visceral adipose tissue? Nonalcoholic fatty liver disease (NAFLD) is often found together with insulin resistance syndrome (4,5) and is commonly found in those suffering from visceral adiposity (3,4). Multiple insulin-related metabolic abnormalities in both organs and tissues have been reported, including impaired insulin-mediated inhibition of hepatic glucose production in livers (4–8), impaired insulin-stimulated glucose metabolism in skeletal muscle tissue (4–9), and impaired insulin-dependent control of lipolysis in adipose tissue (4–10). These metabolic abnormalities are often present along with the increased visceral adipose tissue and a fatty liver. It is very difficult to determine the biological relevance of each anthropometric feature because they are so commonly found together in humans. Recent studies have shown that of these two indicators, i.e., intrahepatic fat content (IHF) and excess visceral adipose tissue, IHF is statistically a more relevant indicator than excess visceral adipose tissue. In insulin-treated type 2 diabetic patients, the IHF content was more …

Abstract 3407: Human omental-derived adipose stem cells support growth of intra-peritoneal ovarian cancer xenografts and increase in-vitro proliferation and migration of ovarian cancer cells

Abstract Introduction: Adipose tissue retains a population of multipotent mesenchymal stromal cells (ASC) which exhibit tumor tropism, similar to bone marrow derived mesenchymal stem cells (MSC); both augment tumor initiation, growth and metastasis. Excess visceral adipose tissue increases the risk of ovarian cancer and the omentum is a frequent site of ovarian cancer metastasis. We hypothesize omentum is a source of ASC which promote ovarian cancer progression. Methods: ASC were isolated from the omentum (O-ASC) of 5 patients with endometrial or ovarian cancer (1-3: early stage/low grade, 4 and 5: IIIC serous ovarian). O-ASC were characterized with flow cytometry and multi-lineage differentiation assays. Luciferase-labeled ovarian cancer cell lines (OVCA433 and OVCA429) were co-cultured with O-ASC and tumor cell proliferation was quantitated using luciferase imaging. Transwell migration assays were performed with OVCA433 and OVCA429 with conditioned media from OSC, MSC, and subcutaneous adipose derived ASC. 9 female NOD.CB17-Prkdc SCID/j mice (age 14 weeks) received: (1) Intraperitoneal (IP) injection of luciferase labeled SCOV3 human ovarian cancer cells or (2) IP injection of luciferase labeled SCOV3 human ovarian cancer cells mixed directly with RFP-labeled hOSC on day 1 and 28. Tumor burden was measured with luciferase imaging and magnetic resonance imaging. Results: O-ASC exhibited mesenchymal morphology, cell surface marker expression similar to MSC (CD45, 0.4%; CD 90, 84.6%;CD44,77.8%;CD 105, 38.5%), osteogenic and adipogenic differentiation. OVCA433 proliferation was significantly increased when co-cultured with O-ASC as compared to control, with a non-significant increase in OVCA429 proliferation observed (average luminescence of 1348.4 vs. 2558.6 p&amp;lt;0.01, 3094.2 vs. 2298.6 p = 0.19 respectively). Migration of OVCA433 was significantly increased compared to tumor cells alone for all 5 OSC lines and MSC line (average absorbance reflecting number of migrated cells 0.15, 0.29. 0.32, 0.45, 0.56 for OSC1-5 and 0.50 MSC respectively, p&amp;lt;0.05 in all cases). Similar trends were seen with OVCA429, with an increase in ovarian cancer cell migration relative to controls in O-ASC 2-5 and MSC. Media from O-ASC 4 and 5, derived from patients with stage III serous ovarian cancer, had the most potent effects on in-vitro migration of OVCA429 and 433 cells. Of the mice bearing IP SKOV3 ovarian tumors, those receiving O-ASC on day 1 and 28 developed larger tumor burden (mean photons/cm2 on day 32 of 1.1 × 107 vs 6.0 × 107, p=0.04). Conclusions: ASC from the omentum can promote proliferation and migration of ovarian cancers. Future studies will determine if patients with advanced cancers have functionally distinct adipose stem cells due to exposure to tumor secreted factors or inherent underlying differences in normal tissue biology. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3407. doi:10.1158/1538-7445.AM2011-3407

Contributions of Cardiorespiratory Fitness and Visceral Adiposity to Six-Year Changes in Cardiometabolic Risk Markers in Apparently Healthy Men and Women

Both excess visceral adipose tissue (VAT) and low cardiorespiratory fitness (CRF) levels are associated with a deteriorated cardiometabolic risk profile. The aim of the study was to examine the respective contributions of changes in VAT accumulation vs. changes in CRF to 6-yr longitudinal changes in cardiometabolic risk markers. We conducted a prospective, population-based study with an average follow-up of 5.9 ± 0.8 yr. We followed 132 middle-aged participants from the Quebec Family Study (mean age, 35.3 ± 13.9 yr). VAT was measured by computed tomography, whereas the level of CRF was assessed by a submaximal physical working capacity test at baseline and at follow-up. A complete cardiometabolic risk profile, including systolic and diastolic blood pressure, fasting glucose and insulin levels, C-reactive protein (n = 72), as well as a standard lipoprotein-lipid profile, was obtained at baseline and at follow-up. We measured changes in CRF, VAT, and cardiometabolic risk profile over 6 yr. After adjusting for age and sex, 6-yr changes in VAT were negatively correlated with changes in CRF (r = -0.38; P < 0.001). In a multivariate model that included age, sex, changes in VAT, changes in CRF, as well as baseline levels of the above cardiometabolic risk factors, 6-yr changes in VAT were the most important predictor of the change in the metabolic syndrome score (R(2) = 13.2%; P < 0.001). Adding 6-yr changes in CRF levels significantly improved the predictability of the model (R(2) = 19.7%; P = 0.002). Changes in both VAT and CRF levels observed over 6 yr are associated with changes in parameters of the lipoprotein-lipid profile, glucose-insulin homeostasis, and inflammatory markers. Thus, maintaining a low level of VAT and a high level of CRF are important targets for maintenance of cardiometabolic health.

Obesity in School Children with Intellectual Disabilities in France

Background The aims of this study were to assess the prevalence of obesity in school children with intellectual disabilities and to determine the most appropriate indicators of obesity measurement. Materials and Methods The weight, height, body mass index (BMI), waist circumference, waist-to-height ratio and body fat percentage as measured by bio-impedance were evaluated in 192 children with intellectual disabilities. Results According to the BMI, 26% of the children were overweight or obese. An excess of body fat was measured in 44.9% of the boys and 47% of the girls. Excess visceral adipose tissue (a high waist-to-height ratio) was identified in 26.4% of the boys and 36.5% of the girls. Conclusions The results indicate the high prevalence of obesity in these children and the heightened risk of developing comorbidities due to visceral adipose tissue. Professional staff should be warned of these potential health problems: early identification and management of excess body fat is the best strategy for preventing obesity and comorbidities in adulthood.