P15.04: Maternal total adipose tissue (TAT) measured by ultrasound and correlations with fasting glucose during first half of pregnancy

Abstract Glucocorticoids play a critical role in metabolic homeostasis. Chronic or excessive activation of the glucocorticoid receptor (GR) in adipose tissue contributes to metabolic disorders such as glucose intolerance and insulin resistance. Steroid-metabolising enzymes in adipose, such as 11β-HSD1 or 5α-reductase, modulate the activation of GR by converting primary glucocorticoids into more or less potent ligands. Carbonyl reductase 1 (CBR1) is a novel regulator of glucocorticoid metabolism, converting corticosterone/cortisol to 20β-dihydrocorticosterone/cortisol (20β-DHB/F); a metabolite which retains GR activity. CBR1 is abundant in adipose tissue and increased in obese adipose of mice and humans1 and increased Cbr1 expression is associated with increased fasting glucose1. We hypothesised that increased Cbr1/20β-DHB in obese adipose contributes to excessive GR activation and worsens glucose tolerance. We generated a novel murine model of adipose-specific Cbr1 over-expression (R26-Cbr1Adpq) by crossing conditional knock-in mice with Adiponectin-Cre mice. CBR1 protein and activity were doubled in subcutaneous adipose tissue of male and female R26-Cbr1Adpq mice compared with floxed controls; corresponding to a two-fold increase 20β-DHB (1.6 vs. 4.2ng/g adipose; P=0.0003; n=5-7/group). There were no differences in plasma 20β-DHB or corticosterone. Bodyweight, lean or fat mass, did not differ between male or female R26-Cbr1Adpq mice and floxed controls. Lean male R26-Cbr1Adpq mice had higher fasting glucose (9.5±0.3 vs. 8.4±0.3mmol/L; P=0.04) and worsened glucose tolerance (AUC 1819±66 vs. 1392±14; P=0.03). Female R26-Cbr1Adpq mice also had a worsened glucose tolerance but fasting glucose was not altered with genotype. There were no differences in fasting insulin or non-esterified fatty acid between genotypes in either sex. Expression of GR-induced genes Pnpla2, Gilz and Per1, were increased in adipose of R26-Cbr1Adpq mice. Following high-fat diet induced obesity, no differences in bodyweight, lean or fat mass, with genotype were observed in male and female mice, and genotype differences in fasting glucose and glucose tolerance were abolished. In conclusion, adipose-specific over-expression of Cbr1 in lean male and female mice led to increased levels of 20β-DHB in adipose but not plasma, and both sexes having worsened glucose tolerance. The influence of adipose CBR1/20β-DHB on glucose tolerance was not associated with altered fat mass or bodyweight and was attenuated by high-fat diet-induced obesity. These metabolic consequences of Cbr1 manipulation require careful consideration given the wide variation in CBR1 expression in the human population, the presence of inhibitors and enhancers in many foodstuffs and the proposed use of inhibitors as an adjunct for cancer treatment regimens. Reference: Morgan et al., Scientific Reports. 2017; 7.

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Abstract 17023: Adipose Tissue Specific Temporal Deletion of Ager Induces Weight Loss in Diet Induced Obese Mice and Improves Glucose Homeostasis

Circulation ◽

10.1161/circ.142.suppl_3.17023 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Robin Wilson ◽

Lakshmi Arivazhagan ◽

Henry Ruiz ◽

Jay Pendse ◽

Laura Frye ◽

...

Keyword(s):

Weight Loss ◽

Body Weight ◽

Adipose Tissue ◽

Glucose Homeostasis ◽

Fasting Glucose ◽

Obese Mice ◽

Gene Encoding ◽

Low Fat Diet ◽

Insulin Tolerance ◽

Specific Deletion

Introduction: The incidence of obesity and its comorbidities is increasing at an alarming rate in US and around the globe. Our previous studies showed that the receptor for advanced glycation end products (RAGE) and its ligands contribute to the pathogenesis of obesity and insulin resistance (IR), as global Ager (gene encoding RAGE) and adipocyte-specific Ager- deleted mice fed a high fat diet (HFD) showed protection from weight gain and IR. However, the role of Ager deletion in mice with established obesity, switched to low fat diet has not been tested. We hypothesize that temporal adipocyte-specific deletion of Ager in obese mice could enhance weight loss and improves glucose homeostasis. Methods: Mice with conditional adipocyte-specific Ager deletion were generated by breeding Ager flox/flox mice with AdipoQ ERT2 Cre recombinase mice resulting in Ager flox/flox / AdipoQ ERT2 Cre (+) and Cre (-) animals. Mice were fed HFD (60% kcal/fat) for 20 weeks starting at 8 weeks of age to establish obesity and were then treated with tamoxifen (TAM) (75 mg/kg per day x 3 alternative days) to induce deletion of Ager . After 4 weeks of TAM treatment, mice were switched to standard chow for 7 weeks and body weight was monitored regularly. Fasting glucose, insulin and glucose tolerance was measured. Results: After 7 weeks of switching to standard chow following TAM, Cre (+) lost significantly more body weight whereas Cre (-) mice showed no significant weight loss over 7 weeks. Furthermore, Cre (+) mice exhibited significantly higher food intake, lower fasting glucose, lower epididymal and inguinal white adipose tissue weights, and improved glucose and insulin tolerance compared to Cre (-) mice. Conclusions: Temporal adipocyte-specific deletion of Ager in mice with established obesity promotes weight loss and improves glucose homeostasis. RAGE may act as a novel therapeutic target in obesity.

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Visceral adipose tissue is associated with poor diet quality and higher fasting glucose in adults with cystic fibrosis

Journal of Cystic Fibrosis ◽

10.1016/j.jcf.2019.01.002 ◽

2019 ◽

Vol 18 (3) ◽

pp. 430-435 ◽

Cited By ~ 5

Author(s):

Moriah P. Bellissimo ◽

Ivana Zhang ◽

Elizabeth A. Ivie ◽

Phong H. Tran ◽

Vin Tangpricha ◽

...

Keyword(s):

Cystic Fibrosis ◽

Adipose Tissue ◽

Visceral Adipose Tissue ◽

Diet Quality ◽

Fasting Glucose ◽

Poor Diet ◽

Visceral Adipose

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Association of PRDM16 rs12409277 and CtBP2 rs1561589 gene polymorphisms with lipid profile of adolescents

Archives of Medical Science ◽

10.5114/aoms/113174 ◽

2021 ◽

Author(s):

Nela Maksimovic ◽

Vanja Vidovic ◽

Tatjana Damnjanovic ◽

Biljana Jekic ◽

Nada Majkic Singh ◽

...

Keyword(s):

Adipose Tissue ◽

Lipid Profile ◽

Total Cholesterol ◽

Ldl Cholesterol ◽

Fasting Glucose ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Cholesterol Levels ◽

Brown Adipose

IntroductionPositive regulatory domain containing 16 (PRDM16) protein represents the key regulator of brown adipose tissue (BAT) development. It induces brown fat phenotype and represses white adipose tissue specific genes through the association with C-terminal binding co-repressor proteins (CtBP1 and CtBP2). In healthy adults presence of BAT has been associated with lower glucose, total cholesterol and LDL (low-density lipoprotein) cholesterol levels. Our aim was to analyze the association of PRDM16 gene (rs12409277) and CtBP2 gene (rs1561589) polymorphisms with body mass index (BMI), fasting glucose level and lipid profile of adolescents.Material and methodsOur study included 295 healthy school children, 145 boys (49.2%) and 150 girls (50.8%), 15 years of age. Genotypes for the selected polymorphisms were detected by the real-time PCR method. Age, gender, height, weight, lipid profile (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides) and fasting glucose levels were recorded.ResultsWe did not find a statistically significant association of rs12409277 and rs1561589 polymorphisms with BMI, fasting glucose and lipid profile of adolescents. We further analyzed the combined effect of the two SNPs and the statistical analysis showed that carriers of CT genotype of rs12409277 polymorphism and GG genotype of rs1561589 polymorphism had significantly lower total cholesterol (p = 0.001) and LDL cholesterol (p = 0.008) levels compared to all other groups of genotypes.ConclusionsOur study suggests that rs12409277 and rs1561589 polymorphism might have an influence on total and LDL cholesterol levels in adolescents. Larger studies should be performed in order to confirm our results.

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Visceral Adiposity Associates With Malnutrition Risk Determined by Royal Free Hospital-Nutritional Prioritizing Tool in Cirrhosis

Frontiers in Nutrition ◽

10.3389/fnut.2021.766350 ◽

2021 ◽

Vol 8 ◽

Author(s):

Xiaoyu Wang ◽

Yifan Li ◽

Mingyu Sun ◽

Gaoyue Guo ◽

Wanting Yang ◽

...

Keyword(s):

Adipose Tissue ◽

Subcutaneous Adipose Tissue ◽

Statistical Significance ◽

Visceral Adiposity ◽

Royal Free Hospital ◽

Significant Difference ◽

Total Adipose Tissue ◽

Male Patients ◽

Visceral Adipose ◽

Subcutaneous Adipose

Mounting evidence has suggested the clinical significance of body composition abnormalities in the context of cirrhosis. Herein, we aimed to investigate the association between visceral adiposity and malnutrition risk in 176 hospitalized patients with cirrhosis. The adiposity parameters were obtained by computed tomography (CT) as follows: total adipose tissue index (TATI), visceral adipose tissue index (VATI), subcutaneous adipose tissue index (SATI), and visceral to subcutaneous adipose tissue area ratio (VSR). Malnutrition risk was screened using Royal Free Hospital-Nutritional Prioritizing Tool (RFH-NPT). Visceral adiposity was determined given a higher VSR based on our previously established cutoffs. Multivariate analysis implicated that male gender (OR = 2.884, 95% CI: 1.360–6.115, p = 0.006), BMI (OR = 0.879, 95% CI: 0.812–0.951, P = 0.001), albumin (OR = 0.934, 95% CI: 0.882–0.989, P = 0.019), and visceral adiposity (OR = 3.413, 95% CI: 1.344–8.670, P = 0.010) were independent risk factors of malnutrition risk. No significant difference was observed regarding TATI, SATI, and VATI among patients with low or moderate and high risk of malnutrition. In contrast, the proportion of male patients embracing visceral adiposity was higher in high malnutrition risk group compared with that in low or moderate group (47.27 vs. 17.86%, p = 0.009). Moreover, this disparity was of borderline statistical significance in women (19.05 vs. 5.88%, p = 0.061). Assessing adipose tissue distribution might potentiate the estimation of malnutrition risk in cirrhotics. It is pivotal to recognize visceral adiposity and develop targeted therapeutic strategies.

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Subcutaneous adipose tissue measurements and better metabolic prediction

Open Medicine ◽

10.2478/s11536-012-0119-4 ◽

2013 ◽

Vol 8 (2) ◽

pp. 237-243 ◽

Cited By ~ 1

Author(s):

Petar Ristic ◽

Dubravko Bokonjic ◽

Vladimir Zivkovic ◽

Vladimir Jakovljevic ◽

Marija Zdravkovic ◽

...

Keyword(s):

Adipose Tissue ◽

Subcutaneous Adipose Tissue ◽

Fasting Glucose ◽

Normal Body Mass Index ◽

Obese Subjects ◽

Homeostatic Model ◽

Subcutaneous Adipose ◽

Anthropometric Markers ◽

Insight Into

AbstractThe aim of the study was to establish the importance of an additional measurement of subcutaneous adipose tissue thickness (SAT) on a predetermined position on the waistline, and its relation to waist measurements as an improvement of metabolic prediction in equally obese subjects. One hundred and forty two consecutive patients were enrolled in the study: stratified by weight as normal (body mass index — BMI 20–25 kg/m2), overweight (BMI 25–30 kg/m2) and obese (BMI >30 kg/m2); and by fasting glucose level as normoglycemic, impaired fasting glucose (IFG), or with type 2 diabetes mellitus (T2DM). SAT was measured in relaxed expiration, 3 cm left of the umbilicus, with ultrasound. Fasting blood samples for glucose, insulin and HbAlc were taken. Waist circumference was slightly higher in the IFG (112.8 cm) and normoglycemic groups (115.62 cm), compared to T2DM (108.15 cm). The T2DM group had a lower average SAT (2.7 cm) than both the IFG group (3.4 cm, p<0.01) and the normoglycemic group (4.2cm, p=0.001). The homeostatic model of assessment for insulin resistance (HOMA IR) was the lowest in normoglycemic and the highest in IFG group. Waistline radius to SAT ratio provides better insight into the deterioration of glucose metabolism than standard anthropometric markers of abdominal obesity in equally obese patients.

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Exenatide with Metformin Ameliorated Visceral Adiposity and Insulin Resistance

Journal of Diabetes Research ◽

10.1155/2018/4019248 ◽

2018 ◽

Vol 2018 ◽

pp. 1-6 ◽

Cited By ~ 3

Author(s):

Xuan Du ◽

Wen Lu ◽

Zijun Lu ◽

Xinyu Shao ◽

Chunhong Hu ◽

...

Keyword(s):

Adipose Tissue ◽

Insulin Sensitivity ◽

Low Income ◽

Sequential Treatment ◽

Diabetic Patients ◽

Type 2 Diabetic Patients ◽

Long Time ◽

Total Adipose Tissue ◽

Type 2 Diabetic

Background. To study the effectiveness of exenatide with metformin and sequential treatment with exenatide and glargine added to metformin and their influence on insulin sensitivity and adipose distribution. Methods. 20 newly diagnosed obese type 2 diabetic patients were enrolled, and 2-month washout treatment of metformin, 6-month exenatide treatment, and 6-month glargine treatment were administrated sequentially accompanied with previous metformin. Glucolipid metabolic parameters were compared among groups. Adipose distribution was quantified with computerized tomography according to anatomy, dividing into visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), adding up to total adipose tissue (TAT). Results. The 6-month exenatide treatment dramatically ameliorated the glucose and lipid profile, improved insulin sensitivity, and mainly decreased VAT and also the ratio of VAT/SAT (RVS). The following 6-month glargine treatment increased VAT. The whole 12-month sequential treatment with exenatide and glargine added to metformin basically improved the insulin sensitivity and glucolipid control though VAT rebounded at the end, however without deteriorating the other parameters. Conclusion. Exenatide is an ideal treatment for obese type 2 diabetic patients in the aspect of adipose tissue distribution. Sequential treatment of exenatide and glargine could be an alternative for low-income patients who cannot afford GLP-1 agonist for long time. This trial is registered with ChiCTR-OOC-17013679.

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Association of total adiposity and computed tomographic measures of regional adiposity with incident cancer risk: a prospective population-based study of older adults

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2013-0360 ◽

2014 ◽

Vol 39 (6) ◽

pp. 687-692 ◽

Cited By ~ 17

Author(s):

Rachel A. Murphy ◽

Taylor F. Bureyko ◽

Iva Miljkovic ◽

Jane A. Cauley ◽

Suzanne Satterfield ◽

...

Keyword(s):

Adipose Tissue ◽

Cancer Risk ◽

Fatty Infiltration ◽

Cox Proportional Hazards ◽

Thigh Muscle ◽

Intermuscular Adipose Tissue ◽

Incident Cancer ◽

Increased Risk ◽

Total Adipose Tissue ◽

Risk Of Cancer

Obesity is associated with increased risk of many types of cancer. Less is known regarding associations between adipose depots and cancer risk. We aimed to explore relationships between adipose depots, risk of cancer, and obesity-related cancer (per NCI definition) in participants initially aged 70–79 years without prevalent cancer (1179 men, 1340 women), and followed for incident cancer for 13 years. Measures included body mass index (BMI), total adipose tissue from dual-energy X-ray absorptiometry, and computed tomography measures of visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue, thigh intermuscular adipose tissue, and thigh muscle attenuation (Hounsfield unit, HU), where low HU indicates fatty infiltration. Hazard ratios (HR) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards models adjusted for demographics, lifestyle variables, and medical conditions. During follow-up, 617 participants developed cancer of which 224 were obesity-related cancers. Total adipose tissue and VAT were positively associated with cancer risk among women (HR 1.14, 95% CI 1.01–1.30 per SD increase; HR 1.15, 95% CI 1.02–1.30 per SD increase). There were no associations with cancer risk among men. Total adipose tissue was positively associated with obesity-related cancer risk among women (HR 1.23, 95% CI 1.03–1.46 per SD increase). VAT was positively associated with obesity-related cancer risk among men (HR 1.30, 95% CI 1.06–1.60 per SD increase) and remained associated even with adjustment for BMI (HR 1.40, 95% CI 1.08–1.82 per SD increase). These findings provide insight into relationships between specific adipose depots and cancer risk and suggest differential relationships among men and women.

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Heterogeneity of abdominal obesity in patients with cardiovascular diseases

Rational Pharmacotherapy in Cardiology ◽

10.20996/1819-6446-2021-12-17 ◽

2022 ◽

Vol 17 (6) ◽

pp. 867-872

Author(s):

S. V. Miklishanskaya ◽

L. V. Solomasova ◽

A. A. Orlovsky ◽

S. N. Nasonova ◽

N. A. Mazur

Keyword(s):

Adipose Tissue ◽

Abdominal Obesity ◽

Metabolic Disorders ◽

Fasting Blood Glucose ◽

Density Lipoprotein ◽

Anthropometric Parameters ◽

Weight Calculation ◽

Total Adipose Tissue ◽

Dimensional Echocardiography ◽

Visceral Adipose

Aim: To assess the content of visceral adipose tissue (VAT) in patients with abdominal obesity and its relationship with metabolic disorders.Material and methods. Patients with abdominal obesity (n=107) were included in the study. All participants had an assessment of anthropometric parameters (height, weight), calculation of body mass index (BMI), proportion of total adipose tissue and VAT (bioimpedance analyzer), high-density lipoprotein cholesterol (HDL-c) levels, triglycerides, fasting blood glucose, epicardial thickness adipose tissue (two-dimensional echocardiography).Results. The median share of VAT (bioimpedance method) was 13%. Patients with abdominal obesity are divided by VAT into 2 groups: ≥14% or ≤13%. Patients with VAT≥14% had significantly higher levels of triglycerides (1.76 [1.27; 2.38] mmol / L) and glucose (6.33 [5.78; 7.87] mmol / L), and below HDL-c levels (0.95 [0.85; 1.21] mmol / L) compared with patients with VAT≤13% (1.32 [1.02; 1.50], 5.59 [5, 11; 6.16] and 1.31 [1.07; 1.58] mmol / L, respectively; p<0.001 for all three comparisons). A significant correlation was found between VAT and triglyceride, glucose and HDL-c levels (r=0.40; r=0.40; r=-0.31, respectively; p<0.001).Conclusion. Persons with abdominal obesity are heterogeneous in the proportion of VAT. The proportion of VAT above the median is associated with metabolic disorders that are significant for the development and progression of atherosclerosis. An increase in BMI in obese individuals is not associated with an increase in VAT and an increase in the severity of metabolic disorders.

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