Intra-abdominal Fat Accumulation Research Articles

The association between waist-to-hip ratio (WHR) with diabetes in the PERSIAN Guilan cohort study population

BackgroundWaist circumference (WC), or waist-to-hip ratio (WHR), potentially offers a more accurate reflection of intra-abdominal fat accumulation and could serve as a superior predictor of type 2 diabetes mellitus (T2DM) risk compared to BMI. The current study investigated the relationship between WHR and its influencing factors among diabetes patients enrolled in the Prospective Epidemiological Research Studies in Iran (PERSIAN) Guilan Cohort study (PGCS).MethodIn this cross-sectional study of 10,520 participants, 2,531 had T2DM. Waist and hip circumference, body mass index (BMI), underlying diseases, and demographical data of participants were recorded. Also, fasting blood sugar (FBS), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides (TG) were assessed. All data was analyzed using SPSS version 16; the significant level was < 0.05.ResultsThe mean age of participants was 51.52 ± 8.90 years, and 39.9% had a BMI between 25 and 30 kg/m2. The prevalence of diabetes was 24.1% (n = 2531). About 7628 (72.5%) individuals had abnormal WHR, and 2072 (19.7%) were diabetics. Among patients with diabetes, abnormal WHR was significantly associated with age over 50, female gender, higher BMI, and lower LDL (P < 0.05).ConclusionThe study showed a higher prevalence of abnormal WHR in diabetic patients. Abnormal WHR in patients with diabetes was significantly associated with age, gender, and BMI.

DXA Android-to-Gynoid Ratio and Cardiovascular Risk Assessment in Age and BMI Propensity-Matched Early Postmenopausal Women.

Background and Objectives: The literature suggests that physiological menopause (MP) seems linked with increased adiposity with a preference for intra-abdominal fat accumulation, greater than what can be attributed only by aging, which could magnify this period's increased cardiovascular risk. Materials and Methods: We retrospectively analyzed two age and body mass index (BMI) propensity-matched subgroups each formed of 90 clinically healthy, 40-60-year-old postmenopausal women, within the first 5 and 5-10 years of MP. The 10-year ASCVD risk was assessed using medical history, anthropometric data, and lipid profile blood tests. The android-to-gynoid (A/G) ratio was computed using Lunar osteodensitometry lumbar spine and hip scans. Results: The A/G ratio was significantly higher for the subgroup evaluated in years 5-10 of MP than in the first 5 years of MP, even after controlling for BMI (1.05 vs. 0.99, p = 0.005). While displaying a significant negative correlation with HDL cholesterol (r = 0.406), the A/G ratio also had positive correlations with systolic blood pressure (BP) values (r = 0.273), triglycerides (r = 0.367), and 10-year ASCVD risk (r = 0.277). After adjusting for smoking, hypertension treatment, and type 2 diabetes, the 10-year ASCVD risk became significantly different for women in the first 5 years (3.28%) compared to those in years 5-10 of MP (3.74%), p = 0.047. Conclusions: In women with similar age and BMI, the A/G ratio appears to vary based on the number of years since menopause onset and correlates with either independent cardiovascular risk parameters like BP, triglycerides, and HDL cholesterol or with composite scores, such as 10-year ASCVD risk.

Electro-acupuncture for central obesity: a patient-assessor blinded, randomized sham-controlled clinical trial

BackgroundCentral obesity is considered as a significant health threat to individuals. Scientific research has demonstrated that intra-abdominal fat accumulation is associated with higher metabolic and cardiovascular disease risks independent of Body Mass Index (BMI). This study aimed to evaluate the efficacy and safety of electro-acupuncture in treating central obesity compared with sham acupuncture.MethodThis was a patient-assessor blinded, randomized, sham-controlled clinical trial. One hundred sixty eight participants aged between 18 and 65 years old with BMI ≥ 25 kg/m2 and waist circumference (WC) of men ≥ 90 cm / women ≥ 80 cm were enrolled and allocated to the acupuncture or sham acupuncture group equally. For the acupuncture group, disposable acupuncture needles were inserted into eight body acupoints, including Tianshu (ST-25), Daheng (SP-15), Daimai (GB-26), Qihai (CV-6), Zhongwan (CV-12), Zusanli (ST-36), Fenglong (ST-40), and Sanyinjiao (SP-6) with electrical stimulation. For the control group, Streitberger’s non-invasive acupuncture needles were utilized at the same acupoints with identical stimulation modalities. The treatment duration was 8 weeks with 2 sessions per week and the follow-up period was 8 weeks. The primary outcome was the change in WC before and after the treatment. The secondary outcomes were the changes in hip circumference, waist-to-hip circumference ratio, BMI, and body fat percentage during the treatment and follow-up period.ResultsThe acupuncture group displayed a significant change in WC compared to the sham group both treatment and follow-up period (MD = -1.1 cm, 95% CI = -2.8 to 4.1). Significant change in body fat percentage was recorded for both groups after treatment but no significance was observed during the follow-up period (MD = -0.1%, 95% CI = -1.9 to 2.2). The changes in hip circumference were also significant both treatment and follow-up period for the acupuncture group (MD = -2.0 cm, 95% CI = -3.7 to -1.7). Compared with sham acupuncture, the body weight (MD = -1 kg, 95% CI = -3.3 to 5.3), BMI (MD = -0.5, 95% CI = -0.7 to 1.9) also decreased significantly within and between groups. The incidence of adverse events was similar in the two groups.ConclusionThis study provided evidence that electro-acupuncture could be effective in treating central obesity by reducing WC, hip circumference, body weight, BMI, and waist-to-hip circumference ratio.Trial registrationClinicalTrials.gov Identifier: NCT03815253, Registered 24 Jan 2019.

Effect of simultaneous intake of rare sugars allitol and D-allulose on intra-abdominal fat accumulation in rats

Allitol, one of the sugar alcohols, is a rare sugar produced by reducing d-allulose contained in Itea, a deciduous shrub belonging to the Saxifrageaceae family. We previously found that the long-term feeding of rats with a diet supplemented with Itea powder suppressed obesity. The present study aimed to further investigate whether this effect on body fat accumulation may be attributed to the simultaneous intake of allitol and d-allulose in Itea. Thirty-two male 3-week-old Wistar rats were randomly divided into four groups of eight. The rats had ad libitum access to the control (C), 3% allitol (A), 3% d-allulose (P), or 3% allitol + 3% d-allulose (AP) diet for 8 weeks, after which the rats were euthanized. d-Allulose significantly lowered the final body weight, weight gain, and quantities of perirenal, mesenteric, and total abdominal adipose tissue. Allitol significantly decreased the mesenteric adipose tissue weight. However, we found no combined effect between d-allulose and allitol on all abdominal fat. The liver glucose-6-phosphate dehydrogenase activity was significantly higher in the d-allulose-supplemented groups. Cecal weight, surface area, and content weight were found to be significantly higher in Groups A and AP than those in Groups C and P, suggesting a higher intestinal fermentability of allitol. Our results suggest that allitol and d-allulose have anti-obesity properties that are affected through different mechanisms but are non-synergistic.

Characterization of hepatic fatty acids using magnetic resonance spectroscopy for the assessment of treatment response to metformin in an eNOS-/- mouse model of metabolic nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease worldwide. Liver biopsy remains the gold standard for diagnosis and staging of disease. There is a clinical need for noninvasive diagnostic tools for risk stratification, follow-up, and monitoring treatment response that are currently lacking, as well as preclinical models that recapitulate the etiology of the human condition. We have characterized the progression of NAFLD in eNOS-/- mice fed a high fat diet (HFD) using noninvasive Dixon-based magnetic resonance imaging and single voxel STEAM spectroscopy-based protocols to measure liver fat fraction at 3T. After 8weeks of diet intervention, eNOS-/- mice exhibited significant accumulation of intra-abdominal and liver fat compared with control mice. Liver fat fraction measured by 1 H-MRS in vivo showed a good correlation with the NAFLD activity score measured by histology. Treatment of HFD-fed NOS3-/- mice with metformin showed significantly reduced liver fat fraction and altered hepatic lipidomic profile compared with untreated mice. Our results show the potential of in vivo liver MRI and 1 H-MRS to noninvasively diagnose and stage the progression of NAFLD and to monitor treatment response in an eNOS-/- murine model that represents the classic NAFLD phenotype associated with metabolic syndrome.

S976 Recent Trends and Mortality Outcomes Among Inflammatory Bowel Disease Patients With and Without Severe Obesity

Introduction: Inflammatory bowel disease (IBD) comprises crohn's disease and ulcerative colitis. Severe obesity (SO) is defined as body mass index (BMI) >40 kg/m2. Obesity is a known risk factor for developing IBD due to accumulation of intra-abdominal fat, cytokine production, alteration of gut microbiome contributing to mucosal inflammation. Using the National Inpatient Sample (NIS), our study examines trends and mortality outcomes among IBD patients with and without SO. Methods: The NIS database was used to identify patients (pts) aged ≥18 years with diagnosis of IBD using ICD-10 codes between 2016-2019. Chi square, ANOVA, and multivariate regression were used to compare significant associations with variables and primary outcome of mortality among pts with IBD stratified by BMI >40 (Severe Obesity-SO) and < 40kg/m2 (Non- severe obesity) . Propensity Score Matching was used to assess the effect of SO and history of bariatric surgery on the outcome of death. STATA MP 17 software was used for analysis. Results: Of the 222,203 pts meeting inclusion criteria, 13,931 (69.61% female; mean age: 54) had SO and 217,633 (55.85% female; mean age: 54) without SO (p=0.23). There was a positive temporal relationship in death rate over time and SO (p=0.00); but a significant negative relationship generally within the IBD population (p=0.02). There was a positive trend in bariatric surgery over time within the general IBD population (p=0.00) and among the IBD-SO subpopulation (p=0.00). Adjusted odds (aOR) of death were 46.73% higher among those with severe obesity compared to other BMI groups (95%CI 1.180-1.865, p=0.00). In propensity score matching analysis, there was a 2.40% higher risk of death in patients with SO compared to non-SO patients (p= 0.03). History of bariatric surgery was associated with 0.70% (p=.026) and 0.85%(p=.01) decreased risk of death in the IBD population and the SO subpopulation compared to those without a history of bariatric surgery, respectively. (Figure) Conclusion: Among IBD pts, severe obesity was associated with increased mortality compared non severe obesity. Nonetheless, bariatric surgery within the entirety of the population was associated with decreased mortality. There may be some mortality benefit associated with higher weights-possibly related to medication side effects or markers of well controlled disease as weight loss itself was associated with increased odds of mortality. More studies are warranted to analyze efficacy of bariatric surgery in other BMI groups.Figure 1.: Demographics and matched study results

PNPLA3 rs738409 C>G Variant Influences the Association Between Visceral Fat and Significant Fibrosis in Biopsy-proven Nonalcoholic Fatty Liver Disease.

Background and AimsIntra-abdominal visceral fat accumulation and patatin-like phospholipase domain containing 3 (PNPLA3) rs738409 G/C gene polymorphism confer a greater susceptibility to nonalcoholic fatty liver disease (NAFLD). We examined whether the relationship between visceral fat accumulation and liver disease severity may be influenced by PNPLA3 rs738409 polymorphism.MethodsThe variant of PNPLA3 rs738409 was genotyped within 523 Han individuals with biopsy-confirmed NAFLD. Visceral fat area (VFA) was measured by bioelectrical impedance. Significant liver fibrosis (SF), defined as stage F ≥2 on histology, was the outcome measure of interest.ResultsThe distribution of PNPLA3 genotypes was CC: 27.5%, CG: 48.2%, and GG: 24.3%. Higher VFA was associated with greater risk of having SF (adjusted-odds ratio [OR]: 1.03; 95% confidence interval [CI]: 1.02–1.04, p<0.05), independent of potential confounders. Among subjects with the same VFA level, the risk of SF was greater among carriers of the rs738409 G genotype than among those who did not. Stratified analysis showed that PNPLA3 rs738409 significantly influenced the association between VFA and SF. VFA remained significantly associated with SF only among the rs738409 G-allele carriers (adjusted-OR: 1.05; 95% CI: 1.03–1.08 for the GG group; and adjusted-OR:1.03; 95% CI: 1.01–1.04 for the GC group). There was a significant interaction between VFA and PNPLA3 rs738409 genotype (Pinteraction=0.004).ConclusionsPNPLA3 rs738409 G allele has a moderate effect on the association between VFA and risk of SF in adult individuals with biopsy-proven NAFLD. Existence of the PNPLA3 rs738409 G allele and VFA interact to increase risk of SF.

Lower High-Density Lipoprotein Cholesterol Concentration Is Independently Associated with Greater Future Accumulation of Intra-Abdominal Fat.

BackgroundBoth intra-abdominal fat (IAF) and high-density lipoprotein cholesterol (HDL-C) are known to be associated with cardiometabolic health. We evaluated whether the accumulation of computed tomography (CT)-measured IAF over 5 years was related to baseline HDL-C concentration in a prospective cohort study.MethodsAll participants were Japanese-Americans between the ages of 34 and 74 years. Plasma HDL-C concentration and CT measurements of IAF, abdominal subcutaneous fat (SCF), and thigh SCF cross-sectional areas were assessed at baseline and at 5-year follow-up visits.ResultsA total of 397 subjects without diabetes were included. The mean±standard deviation HDL-C concentration was 51.6±13.0 mg/dL in men and 66.0±17.0 mg/dL in women, and the IAF was 91.9±48.4 cm2 in men and 63.1±39.5 cm2 in women. The baseline plasma concentration of HDL-C was inversely associated with the change in IAF over 5 years using multivariable regression analysis with adjustment for age, sex, family history of diabetes, weight change over 5 years, and baseline measurements of body mass index, IAF, abdominal SCF, abdominal circumference, thigh SCF, and homeostatic model assessment for insulin resistance.ConclusionThese results demonstrate that HDL-C concentration significantly predicts future accumulation of IAF over 5 years independent of age, sex, insulin sensitivity, and body composition in Japanese-American men and women without diabetes.

Electro-acupuncture for central obesity: randomized, patient-assessor blinded, sham-controlled clinical trial protocol

BackgroundObesity is a common medical condition. Among all the classifications of obesity, central obesity is considered to be a significant threat on the health of individuals. Scientific researches have demonstrated that the accumulation of intra-abdominal fat is associated with higher metabolic and cardiovascular disease risks independently from Body Mass Index (BMI). Our previous research found that the combination of electro-acupuncture and auricular acupressure could significantly reduce the body weight and the BMI compared to sham control group.Methods/designThis is a patient-assessor blinded, randomized, sham-controlled clinical trial on electro-acupuncture for central obesity. One hundred sixty-eight participants with central obesity will be randomly assigned to two groups, which are the acupuncture group and the sham control group. The whole study duration will be 8-week treatment plus 8-week follow up. The primary outcome is the change in waist circumference before and after the treatment. The secondary outcomes include the changes in hip circumference, waist-to-hip circumference ratio, BMI and body fat percentage during the treatment and follow-up.ConclusionThe trial will evaluate the efficacy and safety of electro-acupuncture for central obesity compared with sham acupuncture. The study may provide the solid evidence of electro-acupuncture on central obesity in Hong Kong.Trial registrationClinicalTrials.gov Identifier: NCT03815253,Registered 24 Jan 2019.

Leptin and Adiponectin Concentrations Independently Predict Future Accumulation of Visceral Fat in Nondiabetic Japanese Americans.

Whether leptin and adiponectin are independently associated with regional body fat distribution was investigated in a prospective study of Japanese Americans. Nondiabetic participants 39 to 79 years of age were followed for 5 years to assess change in body composition. Leptin and adiponectin concentrations were evaluated at baseline and by single-slice computed tomography measurements of intra-abdominal fat (IAF), abdominal subcutaneous fat (SCF), and thigh SCF cross-sectional areas at baseline and at 5 years. Ninety-six men and ninety-five women without diabetes had the following baseline mean (SD) values: age 45.7 (3.5) years and 46.4 (3.9) years, IAF 78.7 (38.6) cm2 and 62.1 (39.0) cm2 , leptin concentration 4.5 (2.3) μg/L and 10.2 (5.2) μg/L, and adiponectin concentration 7.4 (3.2) μg/mL and 10.8 (4.7) μg/mL, respectively. Baseline leptin (β = 1.7722, P = 0.014) and adiponectin concentrations (β = -0.4162, P < 0.001) were significantly associated with IAF change over 5 years in multivariable models adjusting for age, sex, diabetes family history, weight change over 5 years, and baseline measurements of BMI, IAF, abdominal SCF, waist circumference, thigh fat, and homeostatic model assessment of insulin resistance. In nondiabetic Japanese Americans, a higher concentration of leptin was associated with greater accumulation of IAF and a higher concentration of adiponectin with lesser accumulation of IAF over 5 years.

Intra-abdominal fat accumulation is an important predictor of metabolic syndrome in young adults.

Metabolic syndrome (MetS), mainly caused by intra-abdominal fat (IAF) accumulation, is an important risk factor for cardiovascular disease. The prevalence of MetS increases rapidly after the age of 40 years, and it is presumed that there is a substantial proportion of MetS in younger age groups. However, the association of IAF with MetS in adults aged 20 to 30 years has not been fully investigated.This study aimed to determine the prevalence of MetS and to verify whether IAF accumulation is associated with other MetS-related metabolic disorders including dyslipidemia, high blood pressure, and high blood glucose among the Japanese population in their 20s.In this cross-sectional study, IAF area (IAFA) and MetS-related metabolic parameters were evaluated in university students in their 20s (n = 1822, 21.5 ± 1.5 years). IAFA was measured using a non-invasive device, DUALSCAN, which can be readily measured through the dual impedance method. The participants were divided into four groups according to IAFA: 0–49.9, 50–74.9, 75–99.9, and ≥100 cm2.MetS was prevalent in 3.3% and 0.0% of the males and females, respectively, according to the Japanese criteria of MetS. The sex- and lifestyle-adjusted odds ratios (ORs) for the three metabolic component levels of Mets were elevated in the larger IAFA groups compared to the smallest IAFA group, according to the level of IAFA. The levels particularly increased in participants with abdominal obesity, defined by both, IAFA and waist circumference rather than by waist circumference alone.IAF accumulation was significantly associated with MetS-related metabolic disorders in young adults. An evaluation of IAFA may contribute to the early prediction of the risk of developing MetS in the future.

Fecal Lipid Content, Serum Lipid Profile, and Intra-Abdominal Fat Accumulation in Normal Rats Supplemented with Rice Bran Oil

This study aimed to investigate the mechanism of rice bran oil on altering lipid absorption and blood lipid level in normal rat. Male Sprague Dawley rat age 3 months old, weighted 250–300 g were grouped into three groups: control (aquabidest 1 ml), orlistat (2.16 mg / 200 g body weight), and rice bran oil (1.04 mg γ-oryzanol / 200 g body weight). The intervention was given through oral gavage, daily for 28 days. Indicators observed were growth performance, total cholesterol and serum triglyceride levels, lipid levels in feces, and accumulation of intra-abdominal fat. The results showed that the treatment did not significantly affect body weight gain. Fecal lipid levels of orlistat, rice bran oil and control group respectively were 0.19g; 0.17g and 0.13 g (p 0.05). The intervention of rice bran oil was shown to reduce blood cholesterol and triglyceride levels in normal mice and did not accumulate intra-abdominal fat. The results suggest that rice bran oil might have an effect on blood lipid regulation but not by preventing lipid absorption.

Relation of visceral fat and haemodynamics in adults with Fontan circulation.

Being overweight is associated with reduced functional capacity in Fontan patients. Increased adiposity leads to accumulation of epicardial and intra-abdominal visceral fat, which produce proinflammatory cytokines and may affect endothelial function. This retrospective study to evaluate the association between visceral fat and Fontan haemodynamics included 23 Fontan patients >18 years old with MRI and catheterization data available. Epicardial fat volume indexed to body surface area was measured by cardiac MRI, and intra-abdominal visceral fat thickness and subcutaneous fat thickness were derived from abdominal MRI. Stepwise regression models were used to determine univariable and multivariable associations between fat measures and haemodynamics. Mean age was 28.2 ± 9.5 years and body mass index was 26 ± 4 kg/m2. Mean central venous pressure was 13 ± 3 mmHg and pulmonary vascular resistance index was 1.23WU·m2 (interquartile range: 0.95-1.56). Epicardial fat volume was associated with age (r2 = 0.37, p = 0.002), weight (r2 = 0.26, p = 0.013), body mass index (r2 = 0.27, p = 0.011), and intra-abdominal visceral fat (r2 = 0.30, p = 0.018). Subcutaneous fat thickness did not relate to these measures. There was modest correlation between epicardial fat volume and pulmonary vascular resistance (r2 = 0.27, p = 0.02) and a trend towards significant correlation between intra-abdominal fat thickness and pulmonary vascular resistance (r2 = 0.21, p = 0.06). Subcutaneous fat thickness was not associated with Fontan haemodynamics. In multivariable analysis, including age and visceral fat measures, epicardial fat was independently correlated with pulmonary vascular resistance (point estimate 0.13 ± 0.05 per 10 ml/m2 increase, p = 0.03). In conclusion, in adults with Fontan circulation, increased visceral fat is associated with higher pulmonary vascular resistance. Excess visceral fat may represent a therapeutic target to improve Fontan haemodynamics.

2057-P: HDL-Cholesterol Concentration Independently Predicts Future Accumulation of Intra-abdominal Fat in Japanese Americans

Background: Both intra-abdominal fat (IAF) and HDL cholesterol (HDL-C) are known to be associated with cardiometabolic health problems, with an inverse correlation between them. However, there is little information about the association between HDL-C concentration with future accumulation of IAF. We conducted a prospective study to evaluate whether baseline HDL-C concentration was associated with the accumulation of CT-measured intra-abdominal fat (IAF) over 5 years. Methods: All participants were Japanese-American men and women between the ages of 34 to 74 years. HDL-C concentration and CT-measurements of IAF, abdominal (SCF) and thigh (TF) subcutaneous fat cross-sectional areas were evaluated at baseline and 5 year follow-up visits. Data were analyzed to determine the association between HDL-C and future 5-year accumulation of IAF. Results: A total of 545 subjects with and without diabetes (296 men, 249 women, and mean age 53.6±11.4 and 54.0±12.0 years, respectively) were included. The mean (SD) HDL-C concentration was 1.3 mmol/L (0.4) in men and 1.7 mmol/L (0.4) in women and mean (SD) IAF was 102 cm2 (53.8) in men and 74.5 cm2 (46.8) in women. Baseline HDL-C concentration was inversely associated with Δ IAF over 5 years using multivariable regression analysis adjusting for age, sex, diabetes family history, weight change over 5 years, and baseline measurements of BMI, IAF, abdominal SCF, abdominal circumference, TF, and HOMA-IR. Conclusions: These results demonstrate that HDL-C concentration predicts significantly future accumulation of IAF over 5 years independent of age, sex, insulin sensitivity, and body composition in nondiabetic Japanese-American men and women. Disclosure S. Song: None. Y. Hwang: None. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk A/S. Consultant; Self; Neurimmune. Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk A/S. D.L. Leonetti: None. W.Y. Fujimoto: None. E.J. Boyko: None. Funding National Institutes of Health DK31170, HL49293); University of Washington (DK017047, DK035816, RR-000037); VA Puget Sound Health Care System (to E.J.B., S.E.K.)

2058-P: Leptin and Adiponectin Concentrations Independently Predict Future Accumulation of Visceral Adiposity in Nondiabetic Japanese Americans

Objectives: The adipokines leptin and adiponectin are associated with change in body composition and are highly correlated, raising questions about whether they exert independent effects. We investigated whether these two adipokines are independently associated with regional body fat accumulation in a prospective study of Japanese Americans. Methods: Nondiabetic participants between the ages of 34 to 74 years were followed for 5 years to assess change in body composition. Leptin and adiponectin concentrations and single slice CT-measurements of intra-abdominal fat (IAF), abdominal (SCF) and thigh (TF) subcutaneous fat cross-sectional areas were evaluated at baseline and 5 year follow-up study visits. Multiple linear regression analysis was used to estimate the association between leptin and adiponectin and future 5-year accumulation of IAF. Results: 96 men and 95 women without diabetes included in this analysis had the following baseline mean (SD) values: age 45.7 (3.5) years and 46.4 (3.9) years; BMI 25.5 (3.1) kg/m2 and 24.0 (3.9) kg/m2; IAF 78.7 (38.6) cm2 and 62.1 (39.0) cm2; leptin concentration 4.5 (2.3) μg/L and 10.2 (5.2) μg/L; and adiponectin concentration 7.4 (3.2) μg/mL and 10.8 (4.7) μg/mL, respectively. Baseline leptin (β = 1.7722, p=0.014) and adiponectin concentrations (β = -0.4162, p&amp;lt;0.001) were significantly associated with ΔIAF over 5 years in multivariable models adjusting for age, sex, diabetes family history, weight change over 5 years, and baseline measurements of BMI, IAF, abdominal SCF, abdominal circumference, TF, and HOMA-IR. Conclusions: In nondiabetic Japanese Americans, baseline concentrations of leptin and adiponectin were independent predictors of IAF accumulation at 5 years. Higher levels of leptin and adiponectin were associated with greater and lesser accumulation of IAF, respectively. These relationships were independent of age, sex, insulin sensitivity, and body composition. Disclosure S. Song: None. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk A/S. Consultant; Self; Neurimmune. Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk A/S. D.L. Leonetti: None. W.Y. Fujimoto: None. E.J. Boyko: None. Funding National Institutes of Health DK31170, HL49293); University of Washington (DK017047, DK035816, RR-000037); VA Puget Sound Health Care System (to E.J.B., S.E.K.)

Interactions of Omentin and Lactotransferrin in the Progression of Metastatic Ovarian Cancer

Advanced stage serous ovarian cancer metastasizes preferentially to the omentum, which is a major site of intra‐abdominal fat accumulation and is covered by a layer of mesothelial cells (mesothelium). Ovarian cancer cells first adhere to and then penetrate through the mesothelium. It was previously shown the expression of adipokine omentin (ITLN1) in mesothelial cells was down‐regulated when mesothelial cells were co‐cultured with ovarian cancer cells. Survival correlation studies demonstrated that patients with serum ITLN1 levels of &gt;350 ng/mL at the time of first treatment experienced longer survival times than those with lower levels of ITLN1. In addition, wound‐healing assay and invasion assay demonstrated that ovarian cancer cells (SKOV3 and A224) treated with physiological levels of ITLN1 showed a significant decrease in motility and invasion potential. However, the molecular mechanism by which ITLN1 modulates these malignant phenotypes remains unknown. Cancer cells migrate using cell‐matrix mechanocoupling mechanisms through paths generated by the degradation and remodeling of the extracellular matrix (ECM) and by force‐mediated deformation (powered by cell traction force from cancer cells). To explore whether omentin suppresses ovarian cancer invasion potential via inhibiting ECM proteolysis, RNA sequencing and pathway analyses were performed on ITLN1 treated cancer cells. Significantly lower levels of MMP1 (matrix metalloproteinase‐1) was found in cancer cells treated with ITLN1 than untreated cells, which was confirmed by qRT‐PCR analysis. Since ITLN1 has been shown to interact with LTF (lactotransferrin), and binding of LTF to its receptors LRP1 (low‐intensity lipoprotein‐receptor‐related protein 1) can transcriptionally upregulate MMP1, an in vitro pull‐down assay on purified LTF and recombinant ITLN1 in serum‐free media was first performed to confirm that ITLN1 interacts and binds with LTF. To determine whether ITLN1 can interfere with the binding of LTF to LRP1 on ovarian cancer cells, a Duolink proximity ligation assay was performed using both anti‐LTF and anti‐LRP1 antibodies. There was a significant decrease in fluorescent signals in cells that were treated with ITLN1 compared to the control. The results suggested that ITLN1 interacts with LTF and prevents LTF from binding to its receptor LRP1 on ovarian cancer cells. Furthermore, ITLN1 abrogated the effects of LTF on MMP1 expression in a dose‐dependent manner in ovarian cancer cells. LTF not only induced MMP1 expression, but also triggered an increase of cytosolic Ca2+ and cell traction force in ovarian cancer cells, which were attenuated by pre‐incubation with ITLN1. Taken together, these data suggest that ITLN1 suppressed LTF's effect on the motility and invasion potential of ovarian cancer cells by decreasing MMP1 expression and cell traction force generation through modulating a calcium dependent LTF‐LRP1 signaling pathway.Support or Funding InformationDepartment of Defense: grant W81XWH‐17‐1‐0146This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Estrogen replacement enhances insulin-induced AS160 activation and improves insulin sensitivity in ovariectomized rats.

Menopause predisposes women to impaired glucose metabolism, but the role of estrogen remains unclear. In this study, we examined the effects of chronic estrogen replacement on whole body insulin sensitivity and insulin signaling in ovariectomized rats. Female Wistar rats aged 9 wk were ovariectomized under anesthesia. After 4 wk, pellets containing either 17β-estradiol (E2) or placebo (Pla) were subcutaneously implanted in the rats. After 4 wk of treatment, the intra-abdominal fat accumulation was greater in the Pla group than that in the E2 group. Hyperinsulinemic-euglycemic clamp analysis and intravenous glucose tolerance test revealed that insulin sensitivity was significantly lower in the Pla group than in the E2 group. In addition, Western blotting showed that in vivo insulin stimulation increased protein kinase B (Akt) phosphorylation to a similar degree in the gastrocnemius and liver of both groups, but phosphorylated Akt2 Ser474 was enhanced in the muscle of the E2 group compared with the Pla group. Moreover, insulin-stimulated phosphorylation of Akt substrate of 160 kDa (AS160) Thr642 was observed only in the E2 group, resulting in the difference between the two groups. Additionally, AS160 protein and mRNA levels were higher in muscle of the E2 group than the Pla group. In contrast, E2 replacement had no effect on glucose transporter 4 protein levels in muscle and glycogen synthase kinase-3β in muscle and liver. These results suggest that estrogen replacement improves insulin sensitivity by activating the Akt2/AS160 pathway in the insulin-stimulated muscle of ovariectomized rats.

Central fat accretion and insulin sensitivity: differential relationships in parous and nulliparous women.

Background/ObjectivesChildbearing is associated with a disproportionate accumulation of visceral fat and an increased risk of metabolic disease. However, it is unknown whether the visceral fat accretion associated with pregnancy modifies a woman’s risk for metabolic disease. The purpose of this study was to test whether the association between abdominal fat and insulin sensitivity differs by parity status in healthy overweight women.Subjects/ MethodsIntra-abdominal adipose tissue (IAAT) via CT, body composition by DXA, insulin sensitivity via intravenous glucose tolerance test and minimal model (SI), HOMA-IR, and cardiorespiratory fitness (VO2max) were assessed in 212 non-diabetic, premenopausal, overweight non-Hispanic white and African American women.ResultsNulliparous women (n=98) were younger, had less IAAT and higher VO2max, but similar SI, HOMA-IR, and leg fat, compared to parous (n=114). In nulliparous women, IAAT was negatively associated with SI, controlling for age, race, and body fat mass (r=−0.40, p<0.001), but this relationship was attenuated in parous women (r=−0.15, p=0.16). In multiple linear regression analysis, leg fat and IAAT were significant predictors of SI in nulliparous, but not parous women.ConclusionsResults suggest that greater IAAT in parous women does not lead to greater insulin resistance; rather, transient insulin resistance during pregnancy may encourage intra-abdominal fat accumulation that is metabolically benign. This underscores the need to consider parity when assessing cardiometabolic risk.

Angiotensin II‐ mediated vasoconstriction of the visceral adipose tissue vasculature is linked to systemic hypertension in obesity

ObjectivesCentral adiposity, in particular the accumulation of intra‐abdominal visceral fat, has been linked to adipose tissue dysfunction and obesity‐related diseases including hypertension and atherosclerosis, however regulatory mechanisms are poorly understood. We hypothesized that increased micro‐vascular tone specifically in visceral fat may contribute to abnormal peripheral vascular resistance.MethodsIn 30 obese subjects(age 42±10 yr, BMI 42±3 kg/m2) undergoing elective bariatric surgery, we characterized vaso‐contractile responses of isolated subcutaneous (SC) and visceral (VIS) adipose tissue arterioles using videomicroscopy, and examined relevant depot‐specific gene expression using qPCR.ResultsVisceral arterioles exhibited significantly greater angiotensin II‐mediated vasoconstriction by 20% in obese hypertensives (OH, SBP 146±8 mmHg) compared to obese normotensives (O, SBP 118±5 mmHg) (p&lt;0.05). Additionally, VIS arterioles showed greater vasoconstriction in response to angiotensin II compared to SC in OH (by 25%, p&lt;0.05) but not in O. Angiotensin converting enzyme (ACE) mRNA expression was significantly increased in VIS compared to SC (2‐fold, p&lt;0.05) in OH but not O. In contrast, vasopressor responses to other agonists including endothelin‐1 and phenylephrine were not different between fat depots or subjects with or without hypertension.ConclusionThe findings demonstrate differential activation of the renin‐angiotensin system (RAS) in the visceral adipose tissue microvasculature that may contribute to mechanisms of systemic hypertension in obesity. RAS targeting, in particular, may provide incremental clinical benefit in treating obesity‐related hypertension.Support or Funding InformationNIH grants P01HL081587 and RO1 HL1145675

The Effect of Estrogen Replacement Therapy on Visceral Fat, Serum Glucose, Lipid Profiles and Apelin Level in Ovariectomized Rats.

ObjectivesOvarian hormones have been shown to regulate body weight, intra-abdominal fat accumulation and plasma level of cytokines. The aim of this study was to investigate the effect of estrogen replacement therapy on visceral adipose tissue, plasma level of apelin, lipid profiles, and glucose in ovariectomized (OVX) rats.MethodsThirty female Wistar rats were divided into OVX (n = 20) and sham (n = 10) groups. OVX rats were subdivided into estrogen replacement therapy (OVX+est; n = 10) receiving 17 β-estradiol valerates (30 µg/kg, s.c., 5 day/week, for eight weeks), and vehicle control group receiving sesame oil same as experiment group (OVX+ses oil; n = 10). After the treatments, all groups were sacrificed and blood samples were collected, visceral fats were taken from the abdominal cavity and weighed immediately. Apelin were measured using enzyme-linked immunosorbent assay kits. Lipid profiles and glucose were measured using the enzymatic colorimetric method. Data were analyzed with one-way analysis of variance and (P < 0.05) determined as the statistical significance level.ResultsAfter eight weeks, body weight, body mass index (BMI), visceral fat, apelin and lipid profiles (P < 0.01) were increased significantly in OVX rats compared to sham group. Treatment with estrogen leads to significant reduction in body weight and BMI (P < 0.05), there was no significant change in serum apelin level in OVX+est rats compared to OVX+ses.ConclusionsThese results suggest that estradiol replacement therapy successfully attenuated some of the metabolic syndrome components, and apelin does not probably stand as a mediator of these physiological functions.