Adipose Tissue Hypoxia Correlates with Adipokine Hypomethylation and Vascular Dysfunction

Obesity is characterized by the accumulation of dysfunctional adipose tissues, which predisposes to cardiometabolic diseases. Our previous in vitro studies demonstrated a role of hypoxia in inducing adipokine hypomethylation in adipocytes. We sought to examine this mechanism in visceral adipose tissues (VATs) from obese individuals and its correlation with cardiometabolic risk factors. We propose an involvement of the hypoxia-inducible factor, HIF1α, and the DNA hydroxymethylase, TET1. Blood samples and VAT biopsies were obtained from obese and non-obese subjects (n = 60 each) having bariatric and elective surgeries, respectively. The analyses of VAT showed lower vascularity, and higher levels of HIF1α and TET1 proteins in the obese subjects than controls. Global hypomethylation and hydroxymethylation were observed in VAT from obese subjects along with promoter hypomethylation of several pro-inflammatory adipokines. TET1 protein was enriched near the promotor of the hypomethylated adipokines. The average levels of adipokine methylation correlated positively with vascularity and arteriolar vasoreactivity and negatively with protein levels of HIF1α and TET1 in corresponding VAT samples, serum and tissue inflammatory markers, and other cardiometabolic risk factors. These findings suggest a role for adipose tissue hypoxia in causing epigenetic alterations, which could explain the increased production of adipocytokines and ultimately, vascular dysfunction in obesity.

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Increased Cardiometabolic Risk Factors and Inflammation in Adipose Tissue in Obese Subjects Classified as Metabolically Healthy

Diabetes Care ◽

10.2337/dc14-0937 ◽

2014 ◽

Vol 37 (10) ◽

pp. 2813-2821 ◽

Cited By ~ 82

Author(s):

Javier Gómez-Ambrosi ◽

Victoria Catalán ◽

Amaia Rodríguez ◽

Patricia Andrada ◽

Beatriz Ramírez ◽

...

Keyword(s):

Risk Factors ◽

Adipose Tissue ◽

Cardiometabolic Risk ◽

Cardiometabolic Risk Factors ◽

Obese Subjects ◽

Metabolically Healthy

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Increased Cardiometabolic Risk Factors and Inflammation in Adipose Tissue in Obese Subjects Classified as Metabolically Healthy. Diabetes Care 2014;37:2813–2821

Diabetes Care ◽

10.2337/dc14-er11 ◽

2014 ◽

Vol 37 (11) ◽

pp. 3132-3132

Author(s):

Javier Gómez-Ambrosi ◽

Victoria Catalán ◽

Amaia Rodríguez ◽

Patricia Andrada ◽

Beatriz Ramírez ◽

...

Keyword(s):

Risk Factors ◽

Adipose Tissue ◽

Diabetes Care ◽

Cardiometabolic Risk ◽

Cardiometabolic Risk Factors ◽

Obese Subjects ◽

Metabolically Healthy

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Relationship Between Meeting 24-Hour Movement Guidelines and Cardiometabolic Risk Factors in Children

Journal of Physical Activity and Health ◽

10.1123/jpah.2017-0090 ◽

2017 ◽

Vol 14 (10) ◽

pp. 779-784 ◽

Cited By ~ 19

Author(s):

Peter T. Katzmarzyk ◽

Amanda E. Staiano

Keyword(s):

Physical Activity ◽

Risk Factors ◽

Blood Pressure ◽

Adipose Tissue ◽

Subcutaneous Adipose Tissue ◽

Cardiometabolic Risk ◽

Vigorous Physical Activity ◽

Density Lipoprotein ◽

Cardiometabolic Risk Factors ◽

Subcutaneous Adipose

Background:The purpose of this study was to evaluate the relationship between adherence to pediatric 24-hour movement guidelines (moderate to vigorous physical activity, sedentary behavior, and sleep) and cardiometabolic risk factors.Methods:The sample included 357 white and African American children aged 5–18 years. Physical activity, television viewing, and sleep duration were measured using questionnaires, and the 24-hour movement guidelines were defined as ≥60 minutes per day of moderate to vigorous physical activity on ≥5 days per week, ≤ 2 hours per day of television, and sleeping 9–11 hours per night (ages 5–13 y) or 8–10 hours per night (ages 14–18 y). Waist circumference, body fat, abdominal visceral and subcutaneous adipose tissue, blood pressure, fasting triglycerides, high-density lipoprotein cholesterol, and glucose were measured in a clinical setting.Results:A total of 26.9% of the sample met none of the guidelines, whereas 36.4%, 28.3%, and 8.4% of the sample met 1, 2, or all 3 guidelines, respectively. There were significant associations between the number of guidelines met and body mass index, visceral and subcutaneous adipose tissue, triglycerides, and glucose. There were no associations with blood pressure or high-density lipoprotein cholesterol.Conclusions:Meeting more components of the 24-hour movement guidelines was associated with lower levels of obesity and several cardiometabolic risk factors. Future efforts should consider novel strategies to simultaneously improve physical activity, sedentary time, and sleep in children.

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Abdominal visceral and subcutaneous adipose tissue and associations with cardiometabolic risk in Inuit, Africans and Europeans: a cross-sectional study

BMJ Open ◽

10.1136/bmjopen-2020-038071 ◽

2020 ◽

Vol 10 (9) ◽

pp. e038071 ◽

Cited By ~ 1

Author(s):

Pernille Falberg Rønn ◽

Gregers Stig Andersen ◽

Torsten Lauritzen ◽

Dirk Lund Christensen ◽

Mette Aadahl ◽

...

Keyword(s):

Risk Factors ◽

Insulin Resistance ◽

Adipose Tissue ◽

Subcutaneous Adipose Tissue ◽

Cardiometabolic Risk ◽

Abdominal Fat ◽

Cardiometabolic Risk Factors ◽

Hepatic Insulin Resistance ◽

Cross Sectional ◽

Subcutaneous Adipose

ObjectivesAbdominal fat has been identified as a risk marker of cardiometabolic disease independent of overall adiposity. However, it is not clear whether there are ethnic disparities in this risk. We investigated the associations of visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (SAT) with cardiometabolic risk factors in three ethnic diverse populations of Inuit, Africans and Europeans.DesignCross-sectional pooled study.SettingGreenland, Kenya and Denmark.MethodsA total of 5113 participants (2933 Inuit, 1397 Africans and 783 Europeans) from three studies in Greenland, Kenya and Denmark were included. Measurements included abdominal fat distribution assessed by ultrasound, oral glucose tolerance test, hepatic insulin resistance, blood pressure and lipids. The associations were analysed using multiple linear regressions.ResultsAcross ethnic group and gender, an increase in VAT of 1 SD was associated with higher levels of hepatic insulin resistance (ranging from 14% to 28%), triglycerides (8% to 16%) and lower high-density lipoprotein cholesterol (HDL-C, −1.0 to −0.05 mmol/L) independent of body mass index. VAT showed positive associations with most of the other cardiometabolic risk factors in Inuit and Europeans, but not in Africans. In contrast, SAT was mainly associated with the outcomes in Inuit and Africans. Of notice was that higher SAT was associated with higher HDL-C in African men (0.11 mmol/L, 95% CI: 0.03 to 0.18) and with lower HDL-C in Inuit (−0.07 mmol/L, 95% CI: -0.12 to –0.02), but not in European men (−0.02 mmol/L, 95% CI: −0.09 to 0.05). Generally weaker associations were observed for women. Furthermore, the absolute levels of several of the cardiometabolic outcomes differed between the ethnic groups.ConclusionsVAT and SAT were associated with several of the cardiometabolic risk factors beyond overall adiposity. Some of these associations were specific to ethnicity, suggesting that ethnicity plays a role in the pathway from abdominal fat to selected cardiometabolic risk factors.

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Epicardial adipose tissue and cardiometabolic risk factors in overweight and obese children and adolescents

Pediatric Obesity ◽

10.1111/j.2047-6310.2012.00134.x ◽

2013 ◽

Vol 9 (1) ◽

pp. 63-70 ◽

Cited By ~ 22

Author(s):

I. Schusterova ◽

F. H. H. Leenen ◽

A. Jurko ◽

F. Sabol ◽

J. Takacova

Keyword(s):

Risk Factors ◽

Adipose Tissue ◽

Children And Adolescents ◽

Cardiometabolic Risk ◽

Epicardial Adipose Tissue ◽

Cardiometabolic Risk Factors ◽

Obese Children

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The Visceral Adiposity Index: Relationship with cardiometabolic risk factors in obese and overweight postmenopausal women – A MONET group study

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2012-0307 ◽

2013 ◽

Vol 38 (8) ◽

pp. 892-899 ◽

Cited By ~ 22

Author(s):

Belinda Elisha ◽

Virginie Messier ◽

Antony Karelis ◽

Lise Coderre ◽

Sophie Bernard ◽

...

Keyword(s):

Risk Factors ◽

Weight Loss ◽

Adipose Tissue ◽

Postmenopausal Women ◽

Cardiometabolic Risk ◽

Area Under The Curve ◽

Weight Loss Program ◽

Cardiometabolic Risk Factors ◽

Visceral Adiposity Index ◽

Visceral Adipose

A recent study suggested visceral adipose index (VAI) as an indicator of adipose tissue distribution and function associated with cardiometabolic risk. We aim to examine the association between VAI and visceral adipose tissue (VAT), insulin sensitivity, and a large panel of associated cardiometabolic risk factors, and to determine if changes in VAI after weight loss intervention will reflect changes in VAT. We performed a secondary analysis using the data of 99 overweight and postmenopausal women that completed a 6-month weight loss program (Montreal Ottawa New Emerging Team Study). VAI was calculated according to the equation by Amato et al. (2010; Diabetes Care, 33(4):920–922). At baseline, VAI was associated with VAT (r = 0.284, p < 0.01) but not with subcutaneous adipose tissue (SAT) while body mass index (BMI) and waist circumference (WC) were significantly related to both. BMI and WC demonstrated significantly stronger predictive value of VAT accumulation (area under the curve = 0.84 and 0.86, respectively) than VAI (area under the curve = 0.61; p < 0.01). However, VAT, BMI, WC, and VAI were similarly related to fasting insulin and glucose disposal rates. After a 6-month weight loss program, VAI decreased significantly and similarly in both intervention groups (p < 0.01). In addition, the percentage of change in VAI showed the significantly weakest correlation (r = 0.25) with the percentage of change in VAT than BMI (r = 0.56; p < 0.01 for r comparisons) and was not a significant predictor of interindividual percentage of change in VAT while BMI accounted for 33.7%. VAI is a weak indicator of VAT function and did not predict changes in VAT after weight loss. Furthermore, this index was not superior to BMI or WC. However, VAI is a good indicator of metabolic syndrome.

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