Adipose and Circulating CCL18 Levels Associate With Metabolic Risk Factors in Women

Context: Cardiometabolic complications in obesity may be linked to white adipose tissue (WAT) dysfunction. Transcriptomic studies of Sc WAT have reported that CCL18, encoding the CC chemokine ligand 18 (CCL18), is increased in obesity/insulin resistance but its functional role is unknown. Objective: Our objectives were to determine if CCL18 is secreted from Sc WAT and if secreted and/or serum levels associate with metabolic phenotypes. We also planned to define the primary cellular source and if CCL18 exerts effects on adipocytes. Design: This is a cohort study. Setting: The study took place in an outpatient academic clinic. Participants: A total of 130 obese women scheduled for bariatric surgery and 35 nonobese controls were included. Methods: Insulin sensitivity was assessed by hyperinsulinemic euglycemic clamp or homeostasis model assessment. CCL18 was analyzed in serum/WAT incubates by ELISA. Effects of recombinant CCL18 was determined in cultures of primary human adipocytes and the monocyte cell line THP-1 differentiated into M0/M1/M2 macrophages. Main Outcome Measure: Association with metabolic risk factors was measured. Results: CCL18 was secreted from WAT and the levels correlated positively with insulin resistance, Adult Treatment Panel III risk score and plasma triglycerides, independent of body mass index and better than other established adipocytokines. In 80 obese women, S-CCL18 levels were significantly higher in insulin resistant compared with insulin sensitive subjects. In WAT CCL18 mRNA was expressed in macrophages and correlated positively with immune-related genes, particularly those enriched in M2 macrophages. While CCL18 increased cyto-/chemokine expression in M0/M2-THP-1 cells, human adipocytes showed no responses in vitro. Conclusions: Circulating and WAT-secreted CCL18 correlates with insulin resistance and metabolic risk score. Because CCL18 is macrophage-specific and associates with adipose immune gene expression, it may constitute a marker of WAT inflammation.

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Associations between Sleep-Disordered Breathing and Metabolic Risk Factors beyond Obesity

Journal of Diabetes Research ◽

10.1155/2018/1567683 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 3

Author(s):

Yusuke Wakabayashi ◽

Rie Oka ◽

Masako Nakaya ◽

Shigehiro Karashima ◽

Mitsuhiro Kometani ◽

...

Keyword(s):

Risk Factors ◽

Insulin Resistance ◽

Sleep Disordered Breathing ◽

Metabolic Risk Factors ◽

Sensitivity Index ◽

Metabolic Risk ◽

Model Assessment ◽

Obstructive Sleep ◽

Low Hdl ◽

Disordered Breathing

Objective. Individuals with multiple metabolic risk factors often experience concomitant sleep-disordered breathing (SDB). We aimed to determine the associations of SDB with individual components of metabolic syndrome independent of obesity.Methods. A cross-sectional study was conducted in 1137 employees aged 30–64 years. Apnea-hypopnea index (AHI) was assessed using a portable monitor for obstructive sleep apnea by admission. Of these, 451 participants took an oral glucose tolerance test to assess homeostatic model assessment of insulin resistance (HOMA-IR) and Matsuda insulin sensitivity index (ISI).Results. The odds ratio (OR) of the highest category of the AHI (≥15 episodes per hour) compared to the lowest one (<5 episodes per hour) was significantly elevated for hypertension, for hypertriglyceridemia, and for low HDL-cholesterolemia when adjusted for age, sex, and alcohol and smoking status (p<0.05). After further adjustment for body mass index (BMI) or waist circumference, the associations for hypertension still remained statistically significant (p<0.05) while those for hypertriglyceridemia and low HDL-cholesterolemia were no longer significant. The association between higher insulin resistance as assessed by HOMA-IR and Matsuda ISI and higher categories of the AHI was also lost after adjustment for BMI.Conclusion. Obesity was a strong confounding factor in the association between SDB and most metabolic risk factors including insulin resistance, except for hypertension. Further longitudinal study is needed to examine the temporal or causal relationships between SDB and metabolic risk factors. This trial is registered with UMIN-CTRUMIN000028067.

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Association between Leptin, Adiponectin, and Leptin/Adiponectin Ratio with Clustered Metabolic Risk Factors in Portuguese Adolescents: The LabMed Physical Activity Study

Annals of Nutrition and Metabolism ◽

10.1159/000477328 ◽

2017 ◽

Vol 70 (4) ◽

pp. 321-328 ◽

Cited By ~ 10

Author(s):

César A. Agostinis-Sobrinho ◽

Edmar Lacerda Mendes ◽

Carla Moreira ◽

Sandra Abreu ◽

Luís Lopes ◽

...

Keyword(s):

Risk Factors ◽

Insulin Resistance ◽

Socioeconomic Status ◽

Mediterranean Diet ◽

Metabolic Risk Factors ◽

Metabolic Risk ◽

Model Assessment ◽

Pubertal Stage ◽

The Mediterranean ◽

Portuguese Adolescents

Introduction: Circulating leptin and adiponectin levels have been associated with impaired vascular function, insulin resistance, and acute cardiovascular evens. This study aimed to evaluate the associations of leptin, adiponectin, and the leptin/adiponectin (L/A) ratio with a clustering of metabolic risk factors (MRF) in adolescents aged 12-18 years. Methods: This is a cross-sectional analysis with 529 Portuguese adolescents aged 12-18 years. Blood samples were taken to analyze total cholesterol (TC) and high-density lipoprotein (HDL) cholesterol (HDL-c), triglycerides glucose, insulin, leptin, and adiponectin levels. A continuous variable of clustered MRF score (sum of Z-scores of body fat percentage, systolic blood pressure, ratio TC/HDL, triglycerides, homeostatic model assessment insulin resistance, and cardiorespiratory fitness*[-1]) was computed. Results: Regression analyses showed that adiponectin was a significant and negative predictor of MRF score (boys: β = -0.199; p < 0.001; girls: β = -0.200; p < 0.001); whereas leptin was a significant positive predictor of MRF score (boys: β = 0.553; p < 0.001; girls: β = 0.399; p < 0.001). The L/A ratio was also a significant positive predictor of MRF score in both sexes (boys: β = 0.593; p < 0.001; girls: β = 0.461; p < 0.001), after adjustments for age, pubertal stage, adherence to the Mediterranean diet, and socioeconomic status. In addition, adiponectin, leptin, and L/A ratio were accurate to predict MRF among adolescents, but L/A ratio showed the highest area under receiver operating characteristic curve. Conclusion: Leptin, adiponectin, and L/A ratio are associated with the clustering of MRF in adolescents after adjustments for age, sex, pubertal stage, adherence to the Mediterranean diet, and socioeconomic status. L/A ratio was more strongly associated with MRF score than adiponectin or leptin.

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Androgens and Glucuronidated Androgen Metabolites Are Associated with Metabolic Risk Factors in Men

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2007-0252 ◽

2007 ◽

Vol 92 (11) ◽

pp. 4130-4137 ◽

Cited By ~ 31

Author(s):

Liesbeth Vandenput ◽

Dan Mellström ◽

Mattias Lorentzon ◽

Charlotte Swanson ◽

Magnus K. Karlsson ◽

...

Keyword(s):

Risk Factors ◽

Insulin Resistance ◽

Young Adult ◽

Fat Mass ◽

Fat Distribution ◽

Metabolic Risk Factors ◽

Metabolic Risk ◽

Model Assessment ◽

Elderly Men ◽

Negatively Associated

Abstract Context: Androgens are associated with metabolic risk factors in men. However, the independent impact of androgens and androgen metabolites on metabolic risk factors in men is unclear. Objective: Our objective was to determine the predictive value of serum levels of androgens and glucuronidated androgen metabolites for metabolic risk factors. Design and Study Subjects: We conducted a population-based study of two Swedish cohorts (1068 young adult and 1001 elderly men). Main Outcome Measures: We measured correlation of serum dihydrotestosterone (DHT), testosterone (T), and glucuronidated androgen metabolites with fat mass, fat distribution, serum lipids, and insulin resistance. Results: Both DHT and T were negatively associated with different measures of fat mass in both cohorts (P < 0.001). Further statistical analysis indicated that DHT, but not T, was independently negatively associated with different measures of fat mass and insulin resistance (P < 0.001). The glucuronidated androgen metabolite androstane-3α,17β-diol-17glucuronide (17G) was independently positively associated with fat mass (P < 0.001). Most importantly, the 17G to DHT ratio was strongly correlated, not only with fat mass but also with central fat distribution, intrahepatic fat, disturbed lipid profile, insulin resistance, and diabetes, explaining a substantial part of the total variance in total body fat (12% in young adult men, 15% in elderly men), the homeostasis model assessment index (10%), and high-density lipoprotein cholesterol (7%). Conclusion: Our findings demonstrate that 17-glucuronidation of the DHT metabolite androstane-3α,17β-diol is strongly associated with several metabolic risk factors in men. Future longitudinal studies are required to determine the possible impact of the 17G to DHT ratio as a metabolic risk factor in men.

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Interleukin-6 G-174C gene polymorphism and serum resistin levels in North Indian women: Potential risk of metabolic syndrome

Human & Experimental Toxicology ◽

10.1177/0960327110393763 ◽

2010 ◽

Vol 30 (10) ◽

pp. 1445-1453 ◽

Cited By ~ 9

Author(s):

A Gupta ◽

V Gupta ◽

AK Singh ◽

S Tiwari ◽

S Agrawal ◽

...

Keyword(s):

Risk Factors ◽

Metabolic Syndrome ◽

Genetic Polymorphism ◽

Interleukin 6 ◽

Metabolic Risk Factors ◽

Metabolic Risk ◽

Obese Women ◽

Resistin Level ◽

Indian Women ◽

Mutant Genotype

The present investigations were aimed to identify the possible association between genetic polymorphism in interleukin-6 (IL-6) G-174C gene, which confers susceptibility to metabolic syndrome, and serum level of resistin in North Indian women. The study population comprised 370 unrelated Indian women (192 having abdominal obesity and 178 controls). Polymorphism in genotype (CC+GC) of IL-6 G-174C gene was determined using a combination of polymerase chain reaction (PCR) and sequence-specific primer with restriction fragment length polymorphism (RFLP) technology. Insulin resistance (IR) and serum resistin level were also analyzed along with metabolic risk factors. Of 192 abdominal obese women, 147 (76.56%) were found to have mutant CC+GC ( p = 0.001) genotype and allele frequency ( p = 0.001), which was significantly higher 45 (23.44%) than non-obese and their respective wild type. The mutant genotype (CC+GC) of IL-6 gene was found to be associated significantly with high triglyceride ( p = 0.025) and resistin level ( p < 0.001), when compared with respective wild genotype (GG) in obese women. Non-obese women with no signs of metabolic risk factors were found to have significantly low level of serum resistin and IR in comparison to obese women having genetic polymorphism for IL-6 G-174C gene. Study suggests that IL-6 G-174C gene is one among the susceptibility loci for metabolic syndrome in North Indian women. Genotype for this polymorphism may prove informative for prediction of genetic risk for metabolic syndrome. Further, high level of serum resistin molecules may be targeted to correlate with metabolic syndrome risk factors and could be used as early prediction marker.

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Treating insulin resistance in hypertension with metformin reduces both blood pressure and metabolic risk factors

Journal of Internal Medicine ◽

10.1111/j.1365-2796.1991.tb00328.x ◽

1991 ◽

Vol 229 (2) ◽

pp. 181-187 ◽

Cited By ~ 158

Author(s):

K. LANDIN ◽

L. TENGBORN ◽

U. SMITH

Keyword(s):

Risk Factors ◽

Insulin Resistance ◽

Blood Pressure ◽

Metabolic Risk Factors ◽

Metabolic Risk

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Multinutrient supplement containing ephedra and caffeine causes weight loss and improves metabolic risk factors in obese women: a randomized controlled trial

International Journal of Obesity ◽

10.1038/sj.ijo.0803283 ◽

2006 ◽

Vol 30 (10) ◽

pp. 1545-1556 ◽

Cited By ~ 46

Author(s):

R M Hackman ◽

P J Havel ◽

H J Schwartz ◽

J C Rutledge ◽

M R Watnik ◽

...

Keyword(s):

Risk Factors ◽

Weight Loss ◽

Randomized Controlled Trial ◽

Controlled Trial ◽

Metabolic Risk Factors ◽

Metabolic Risk ◽

Obese Women ◽

Randomized Controlled

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Randomized Controlled Trial of A 12-Week Yoga-Based (Including Diet) Lifestyle vs. Dietary Intervention on Cardio-Metabolic Risk Factors and Continuous Risk Score in Indian Adults with Metabolic Syndrome

Behavioral Medicine ◽

10.1080/08964289.2018.1538098 ◽

2019 ◽

Vol 46 (1) ◽

pp. 9-20 ◽

Cited By ~ 1

Author(s):

Rashmi Yadav ◽

Raj Kumar Yadav ◽

Rajesh Khadgawat ◽

Ravindra Mohan Pandey ◽

Ashish Datt Upadhyay ◽

...

Keyword(s):

Risk Factors ◽

Metabolic Syndrome ◽

Randomized Controlled Trial ◽

Risk Score ◽

Dietary Intervention ◽

Controlled Trial ◽

Metabolic Risk Factors ◽

Metabolic Risk ◽

Randomized Controlled

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Vitamin D in relation to metabolic risk factors, insulin sensitivity and adiponectin in a young Middle-Eastern population

Acta Endocrinologica ◽

10.1530/eje-08-0952 ◽

2009 ◽

Vol 160 (6) ◽

pp. 965-971 ◽

Cited By ~ 108

Author(s):

Marie-Hélène Gannagé-Yared ◽

Rima Chedid ◽

Simon Khalife ◽

Emmanuel Azzi ◽

Fernand Zoghbi ◽

...

Keyword(s):

Risk Factors ◽

Blood Pressure ◽

Ldl Cholesterol ◽

Middle Eastern ◽

Density Lipoprotein ◽

Multivariate Regression Analysis ◽

Metabolic Risk Factors ◽

Metabolic Risk ◽

Model Assessment ◽

Homa Index

ObjectivesSeveral studies suggest a link between circulating 25-hydroxyvitamin D (25(OH)D) and metabolic risk factors. However, this relation has been mainly studied in elderly and/or obese subjects. In addition, the relation between 25(OH)D and adiponectin is unclear. The purpose of this study is to look at these relations in non-obese young individuals.DesignWe investigated the relation between serum 25(OH)D and adiposity, blood pressure, glucose metabolism, lipid profile, and adiponectin in 381 randomly selected university students (201 males and 180 females, mean age 23.9±3.9).ResultsIn the overall population, 25(OH)D is significantly inversely correlated with body mass index (BMI), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), insulin levels, and homeostasis model assessment of insulin resistance (HOMA index) and positively correlated with adiponectin and high density lipoprotein-cholesterol (P<0.01 for all variables). In males, these correlations are still significant for BMI, SBP, WC, and adiponectin (P=0.02,P=0.01,P=0.04 andP=0.01 respectively); also, 25(OH)D is inversely correlated with low density lipoprotein (LDL)-cholesterol (P=0.007). In females, 25(OH)D is only inversely correlated with FPG and HOMA index (P<0.001 andP=0.03 respectively). In multivariate regression analysis models, after adjustment for sex and BMI, 25(OH)D is an independent predictor of FPG and SBP (P=0.032 andP=0.05 respectively) in the overall population, while in males 25(OH)D is a predictor of LDL-cholesterol and SBP independently of BMI (P=0.007 andP=0.035 respectively).ConclusionIn non-obese young subjects, we observe new relationships between 25(OH)D and several metabolic risk factors and adiponectin. Further research is needed to elucidate the gender differences and to look at the relation between 25(OH)D and adiponectin.

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