Circulating IL-6, clusterin and irisin in obese subjects with different grades of obesity: association with insulin resistance and sexual dimorphism

OBJECTIVE: Adipose tIssue regulates insulin sensitivity via the circulating adipocytokines, leptin, resistin and adiponectin. The objective of this study was to compare the levels of resistin, adiponectin and leptin in lean and obese subjects and determine the relationship between circulating adipocytokines and insulin resistance. METHODS: We examined plasma levels of resistin, adiponectin and leptin in 17 lean subjects with a mean body mass index (BMI) of approximately 23 and 34 non-diabetic obese individuals with a mean BMI approximately 33. Insulin resistance was assessed using the homeostasis model assessment ratio (HOMA-R) formula derived from fasting insulin and glucose levels. RESULTS: Resistin levels were not significantly different between the two groups but were significantly higher in women compared with men, 35.4+/-6.5 (s.e.) vs 15.4+/-2.9 microg/L, P<0.01. Resistin did not correlate with BMI but did significantly correlate with HOMA-R, P<0.01, and this correlation remained significant after adjustment for gender and BMI. Adiponectin levels were significantly lower in obese compared with lean subjects, P<0.005, and higher in women, P<0.001, but showed no significant correlation with HOMA-R. Leptin levels were significantly higher in obese subjects and women and correlated with HOMA-R and resistin. DISCUSSION: In this small group of patients we demonstrated that insulin resistance correlated most strongly with leptin levels. A significant correlation between resistin levels and insulin resistance was also observed. Although a similar trend was apparent for adiponectin, the correlation with insulin resistance did not achieve statistical significance.

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NF-κB-Inducing Kinase (NIK) Mediates Skeletal Muscle Insulin Resistance: Blockade by Adiponectin

Endocrinology ◽

10.1210/en.2011-1343 ◽

2011 ◽

Vol 152 (10) ◽

pp. 3622-3627 ◽

Cited By ~ 26

Author(s):

Sanjeev Choudhary ◽

Sandeep Sinha ◽

Yanhua Zhao ◽

Srijita Banerjee ◽

Padma Sathyanarayana ◽

...

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Glucose Uptake ◽

Kinase Activity ◽

Pi3 Kinase ◽

Dominant Negative ◽

Muscle Insulin Resistance ◽

Akt Phosphorylation ◽

Skeletal Muscle Insulin Resistance ◽

Obese Subjects

Enhanced levels of nuclear factor (NF)-κB-inducing kinase (NIK), an upstream kinase in the NF-κB pathway, have been implicated in the pathogenesis of chronic inflammation in diabetes. We investigated whether increased levels of NIK could induce skeletal muscle insulin resistance. Six obese subjects with metabolic syndrome underwent skeletal muscle biopsies before and six months after gastric bypass surgery to quantitate NIK protein levels. L6 skeletal myotubes, transfected with NIK wild-type or NIK kinase-dead dominant negative plasmids, were treated with insulin alone or with adiponectin and insulin. Effects of NIK overexpression on insulin-stimulated glucose uptake were estimated using tritiated 2-deoxyglucose uptake. NF-κB activation (EMSA), phosphatidylinositol 3 (PI3) kinase activity, and phosphorylation of inhibitor κB kinase β and serine-threonine kinase (Akt) were measured. After weight loss, skeletal muscle NIK protein was significantly reduced in association with increased plasma adiponectin and enhanced AMP kinase phosphorylation and insulin sensitivity in obese subjects. Enhanced NIK expression in cultured L6 myotubes induced a dose-dependent decrease in insulin-stimulated glucose uptake. The decrease in insulin-stimulated glucose uptake was associated with a significant decrease in PI3 kinase activity and protein kinase B/Akt phosphorylation. Overexpression of NIK kinase-dead dominant negative did not affect insulin-stimulated glucose uptake. Adiponectin treatment inhibited NIK-induced NF-κB activation and restored insulin sensitivity by restoring PI3 kinase activation and subsequent Akt phosphorylation. These results indicate that NIK induces insulin resistance and further indicate that adiponectin exerts its insulin-sensitizing effect by suppressing NIK-induced skeletal muscle inflammation. These observations suggest that NIK could be an important therapeutic target for the treatment of insulin resistance associated with inflammation in obesity and type 2 diabetes.

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Improvement in Glucose Tolerance and Insulin Resistance in Obese Subjects Treated with Troglitazone

New England Journal of Medicine ◽

10.1056/nejm199411033311803 ◽

1994 ◽

Vol 331 (18) ◽

pp. 1188-1193 ◽

Cited By ~ 615

Author(s):

John J. Nolan ◽

Bernhard Ludvik ◽

Patricia Beerdsen ◽

Mary Joyce ◽

Jerrold Olefsky

Keyword(s):

Insulin Resistance ◽

Glucose Tolerance ◽

Obese Subjects

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Brain Iron Overload, Insulin Resistance, and Cognitive Performance in Obese Subjects: A Preliminary MRI Case-Control Study

Diabetes Care ◽

10.2337/dc14-0664 ◽

2014 ◽

Vol 37 (11) ◽

pp. 3076-3083 ◽

Cited By ~ 30

Author(s):

Gerard Blasco ◽

Josep Puig ◽

Josep Daunis-i-Estadella ◽

Xavier Molina ◽

Gemma Xifra ◽

...

Keyword(s):

Insulin Resistance ◽

Iron Overload ◽

Cognitive Performance ◽

Case Control Study ◽

Case Control ◽

Brain Iron ◽

Obese Subjects ◽

Control Study

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The apelinergic system: Sexual dimorphism and tissue-specific modulations by obesity and insulin resistance in female mice

Peptides ◽

10.1016/j.peptides.2013.05.013 ◽

2013 ◽

Vol 46 ◽

pp. 94-101 ◽

Cited By ~ 14

Author(s):

Laura Butruille ◽

Anne Drougard ◽

Claude Knauf ◽

Emmanuelle Moitrot ◽

Philippe Valet ◽

...

Keyword(s):

Insulin Resistance ◽

Sexual Dimorphism ◽

Tissue Specific ◽

Female Mice

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Circulating Level of Soluble Leptin Receptor and its Association with Cardiometabolic Risk Factors among Obese Subjects in Kerala, South India

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i28b31557 ◽

2021 ◽

pp. 232-239

Author(s):

K. S. Manju ◽

K. B. Leena ◽

L. Vijayalekshmi ◽

K. T. Shenoy

Keyword(s):

Risk Factors ◽

Insulin Resistance ◽

Cardiometabolic Risk ◽

Leptin Receptor ◽

Obese Group ◽

Serum Leptin ◽

Control Subjects ◽

Soluble Leptin Receptor ◽

Significant Difference ◽

Obese Subjects

Background and Aims: Leptin, the peptide hormone secreted mainly by adipose tissue is reported to play the central role in the pathogenesis of obesity. Leptin exerts its biological effects through specific receptor molecules present in target tissues. Among the different isoforms of leptin receptor, the Soluble Leptin Receptor (SLR) is the major leptin binding protein seen in circulation which modulates the bioavailability of leptin. Our objectives were to analyse the level of circulating SLR among obese subjects and its association with biomarkers of obesity, serum leptin, insulin and cardiometabolic risk factors in comparison with healthy age and sex matched control subjects. Methods: About 173 study participants of both genders were selected and grouped as case (n=102) and control (n=71) with a cut off point of BMI 25kg/m2. Waist to hip ratio (WHR) and body fat percentage (BF%) were calculated from anthropometric measurements. Leptin, insulin, soluble leptin receptor were estimated in fasting blood samples by sandwich ELISA method. Fasting plasma glucose and lipid profile were measured by standard enzymatic methods in autoanalyzer. Homeostasis Model Assessment of Insulin resistance (HOMA-IR) was calculated. Comparison between groups was done by independent sample ‘t’ test. P values <.05 were considered statistically significant. Results: The SLR level was found to be increased in obese group in comparison with control group(P =.001). A significant increase in serum leptin and insulin level was observed in obese group when compared to control (P =.001). Obese group showed more than two fold increase in insulin resistance expressed as HOMA-IR when compared to control subjects (P =.001). But no significant difference in the synthesis of insulin expressed as HOMA-beta between the groups. No significant difference in serum lipoprotein levels was observed between the two groups. Conclusion: Increased level of circulating soluble leptin receptor has been observed in obese subjects in comparison with control subjects and is associated with hyperleptinemia, hypertension and insulin resistance.

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Changes of Insulin Resistance and Adipokines Following Supplementation with Glycyrrhiza Glabra L. Extract in Combination with a Low-Calorie Diet in Overweight and Obese Subjects: a Randomized Double Blind Clinical Trial

Advanced Pharmaceutical Bulletin ◽

10.15171/apb.2018.015 ◽

2018 ◽

Vol 8 (1) ◽

pp. 123-130 ◽

Cited By ~ 3

Author(s):

Mohammad Alizadeh ◽

Nazli Namazi ◽

Elham Mirtaheri ◽

Nafiseh Sargheini ◽

Sorayya Kheirouri

Keyword(s):

Insulin Resistance ◽

Clinical Trial ◽

Glycyrrhiza Glabra ◽

Double Blind ◽

Low Calorie ◽

Low Calorie Diet ◽

Double Blind Clinical Trial ◽

Calorie Diet ◽

Obese Subjects ◽

Glycyrrhiza Glabra L

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Biochemical and clinical characterization of metabolic phenotypes: a cross-sectional study from Maracaibo city, Venezuela

F1000Research ◽

10.12688/f1000research.13897.2 ◽

2019 ◽

Vol 7 ◽

pp. 230

Author(s):

Valmore Bermudez ◽

Joselyn Rojas ◽

Juan Salazar ◽

Maria Sofia Martinez ◽

Luis Carlos Olivar ◽

...

Keyword(s):

Insulin Resistance ◽

Coronary Event ◽

Cross Sectional Study ◽

Normal Weight ◽

Related Factors ◽

Cross Sectional ◽

Metabolic Phenotypes ◽

Event Risk ◽

Obese Subjects ◽

Healthy Obese

Background: In 1980, Reuben Andresen observed that in certain individuals, obesity did not increase mortality, introducing an atypical phenotype called “healthy obese”. Other studies reported that 10-15 % of lean individuals presented insulin resistance, hyperglycemia and dyslipidemia. The objective of this study was to evaluate biochemical and clinical characteristics of metabolic phenotypes in Maracaibo city. Methods: A descriptive, cross-sectional sub-analysis of The Maracaibo City Metabolic Syndrome Prevalence Study, with a randomized multistage sampling was performed including 1226 non diabetic individuals from both sexes. For phenotype definition, the subjects were first classified according to their BMI into Normal-Weight, Overweight and Obese; then divided in metabolically healthy and unhealthy using a two-step analysis cluster being predictive variables: HOMA2-IR, HOMA2-βcell, triglycerides. To evaluate the relationship with coronary risk, a multiple logistic regression model was performed. Results: In the studied population, 43.9% (n=538) were healthy normal weight, 5.2% (n=64) unhealthy normal weight, 17.4% (n=217) healthy obese and 33.5% (n=411) unhealthy obese subjects. Atypical phenotypes, Metabolically Unhealthy Normal-Weight (MUNW) was more frequent in males (56.3%), whereas Metabolically Unhealthy Obese (MUO) was more frequent in females (51.3%). This phenotypes had a higher coronary event risk, especially for obese individuals (MHO: OR=1.85 CI95%: 1.11-3.09; p=0.02 and MUO: OR=2.09 CI95%: 1.34-3.28; p<0.01). Conclusion: Individuals with atypical metabolic phenotypes are common in Maracaibo city. Related factors may include insulin resistance, basal glucose, and triglycerides levels. Lastly, obese subjects show a higher coronary event risk even those with normal metabolic status.

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