scholarly journals Rosiglitazone Elicits an Adiponectin-Mediated Insulin-Sensitizing Action at the Adipose Tissue-Liver Axis in Otsuka Long-Evans Tokushima Fatty Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Jia Li ◽  
Yao-Ming Xue ◽  
Bo Zhu ◽  
Yong-Hua Pan ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Protein Expression ◽  
Inflammatory Responses ◽  
Oral Glucose ◽  
Model Assessment ◽  
Insulin Sensitizer ◽  
Nonesterified Fatty Acids ◽  
Fasting Plasma ◽  
Long Evans

Rosiglitazone is an agonist of peroxisome proliferator-activated receptor- (PPAR-) γ that is principally associated with insulin action. The exact mechanisms underlying its insulin-sensitizing action are still not fully elucidated. It is well known that adiponectin mostly secreted in adipose tissue is an insulin sensitizer. Here, we found that treatment of Otsuka Long-Evans Tokushima Fatty (OLETF) rats with rosiglitazone (3 mg/kg, once daily, by oral gavage for 33 weeks) attenuated the increase in fasting plasma insulin concentrations and the index of the homeostasis model assessment of insulin resistance along with the age growth and glucose concentrations during an oral glucose tolerance test. In addition, the increase in plasma alanine aminotransferase activity, concentrations of fasting plasma nonesterified fatty acids and triglyceride, and hepatic triglyceride content was also suppressed. The hepatic protein expression profile revealed that rosiglitazone increased the downregulated total protein expression of insulin receptor substrate 1 (IRS-1) and IRS-2. Furthermore, the treatment suppressed the upregulated phosphorylation of IRS-1 at Ser307 and IRS-2 at Ser731. The results indicate that rosiglitazone ameliorates hepatic and systemic insulin resistance, hepatic inflammation, and fatty liver. Mechanistically, rosiglitazone suppressed hepatic protein overexpression of both phosphorylated nuclear factor- (NF-) κBp65 and inhibitory-κB kinase-α/β, a transcription factor that primarily regulates chronic inflammatory responses and the upstream NF-κB signal transduction cascades which are necessary for activating NF-κB, respectively. More importantly, rosiglitazone attenuated the decreases in adipose adiponectin mRNA level, plasma adiponectin concentrations, and hepatic protein expression of adiponectin receptor-1 and receptor-2. Thus, we can draw the conclusion that rosiglitazone elicits an adiponectin-mediated insulin-sensitizing action at the adipose tissue-liver axis in obese rats. Our findings may provide new insights into the mechanisms of action of rosiglitazone.

Targeted inhibition of CD74 attenuates adipose COX-2-MIF-mediated M1 macrophage polarization and retards obesity-related adipose tissue inflammation and insulin resistance

2018 ◽  
Vol 132 (14) ◽  
pp. 1581-1596 ◽  
Author(s):  
Pei-Chi Chan ◽  
Ting-Ni Wu ◽  
Ying-Chuan Chen ◽  
Chieh-Hua Lu ◽  
Martin Wabitsch ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Inflammatory Responses ◽  
Macrophage Polarization ◽  
Mrna Levels ◽  
Model Assessment ◽  
M1 Macrophage ◽  
Cox 2 ◽  
Highly Correlated ◽  
Targeted Inhibition

Adipose tissue (AT) inflammation is crucial to the development of obesity-associated insulin resistance. Our aim was to investigate the contribution of cyclooxygenase-2 (COX-2)/macrophage migration inhibitory factor (MIF)-mediated cross-talk between hypertrophic adipocytes and macrophages to the etiology of AT inflammation and the involvement of CD74 using human SGBS adipocytes, THP-1 macrophages and mice fed a high-fat (HF) diet. The MIF and CD74 mRNA levels in the adipocytes and stromal vascular cells (SVCs) of white fat were highly correlated with body weight (BW), homeostatic model assessment for insulin resistance (HOMA-IR), and adipose macrophage marker expression levels, especially those in SVCs. COX-2 inhibition suppressed the elevation of MIF production in HF white adipocytes as well as palmitate and hypoxic-treated SGBS adipocytes. Treatment of adipocytes transfected with shCOX-2 and siMIF or subjected to MIF depletion in the medium reversed the pro-inflammatory responses in co-incubated THP-1 cells. Inhibition of NF-κB activation reversed the COX2-dependent MIF secretion from treated adipocytes. The targeted inhibition of macrophage CD74 prevented M1 macrophage polarization in the above co-culture model. The COX-2-dependent increases in CD74 gene expression and MIF release in M1-polarized macrophages facilitated the expression of COX-2 and MIF in co-cultured SGBS adipocytes. CD74 shRNA intravenous injection suppressed HF-induced AT M1 macrophage polarization and inflammation as well as insulin resistance in mice. The present study suggested that COX-2-mediated MIF secretion through NF-κB activation from hypertrophic and hypoxic adipocytes as well as M1 macrophages might substantially contribute to the phenotypic switch of AT macrophages through CD74 in obesity. Inhibition of CD74 could attenuate AT inflammation and insulin resistance in the development of HF diet-induced obesity.

scholarly journals The Effect of Tianmai Xiaoke Pian on Insulin Resistance through PI3-K/AKT Signal Pathway

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Nana Wang ◽  
Tiegang Li ◽  
Ping Han
Keyword(s):  
Insulin Resistance ◽  
Fasting Blood Glucose ◽  
Area Under The Curve ◽  
Diabetic Rats ◽  
Signal Pathway ◽  
Chromium Picolinate ◽  
Oral Glucose ◽  
Model Assessment ◽  
Insulin Sensitizer ◽  
Type 2 Diabetic Mellitus

In the clinical setting, given the potential adverse effects of thiazolidinediones and biguanides, we often have difficulty in treatment that no other insulin sensitizers are available for use in type 2 diabetic mellitus (T2DM) patients. Tianmai Xiaoke Pian (TMXKP) is a traditional Chinese medicine tablet, which is comprised of chromium picolinate, Tianhuafen, Maidong, and Wuweizi. To understand its mechanism of action on insulin resistance, TMXKP (50 mg/kg orally) was tested in T2DM rats (induced by a high-fat diet and streptozotocin). Eight weeks later, fasting blood glucose (FBG) and oral glucose tolerance tests (OGTT) were performed. Area under the curve (AUC) and homeostatic model assessment of insulin resistance (HOMA-IR) were calculated, and PI3-K/AKT signal pathway-related genes and proteins were tested by reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis in muscle, adipose, and liver tissues, respectively. TMXKP significantly reduced FBG, OGTT, AUC, and HOMA-IR in diabetic ratsP<0.05. Furthermore, we also observed that TMXKP could significantly decreaseIRS-1,IRS-2,PI3-K p85α, andAKT2gene expression and also IRS-1, IRS-2, PI3-K, AKT2, and p-AKT2 protein expression levelsP<0.05in diabetic rats. These findings confirm that TMXKP can alleviate insulin resistance in T2DM rats through the PI3K/AKT pathway. Thus TMXKP appears to be a promising insulin sensitizer.

scholarly journals Anti-diabetic Activity of Triphala Fruit Extracts, Individually and in Combination, in a Rat Model of Insulin Resistance

2008 ◽  
Vol 3 (2) ◽  
pp. 1934578X0800300
Author(s):  
Venkateshan S. Prativadibhayankaram ◽  
Samir Malhotra ◽  
Promila Pandhi ◽  
Amritpal Singh
Keyword(s):  
Insulin Resistance ◽  
Rat Model ◽  
Hypoglycemic Activity ◽  
Oral Glucose ◽  
Model Assessment ◽  
Emblica Officinalis ◽  
High Fructose Diet ◽  
Fruit Extracts ◽  
Fasting Plasma ◽  
High Fructose

We have investigated the possible antidiabetic properties of fruit extracts of Emblica officinalis Gaertn., Terminalia chebula Retz. and T. bellirica Roxb., individually and in combination (Triphala) in a high fructose diet induced rat model of insulin resistance. In the first part of the study, normal animals were studied for hypoglycemic activity. In the second part, animals were given a high fructose diet (HFD) for 40 days, for the last 20 days of which fruit extracts were also given. Body weight, fasting plasma glucose (FPG), and area under the curve (AUC) of the oral glucose tolerance test (OGTT) were assessed at the baseline, and at days 20 and 40. Fasting plasma insulin levels and the homeostasis model assessment (HOMA) resistance index were also assessed at baseline, 20 and 40 days. Fasting lipid levels were measured at the end of the study. During the first part of the investigation, in which extracts were given to normal animals, T. chebula showed significant hypoglycemic activity. During the second part of the study, in which the extracts were given to HFD fed rats, T. chebula caused a significant decrease in FPG and AUC. Emblica officinalis and Triphala caused a normalization of FPG. T. bellirica caused a reduction in AUC levels, but had no effect on FPG levels. T. bellirica caused a reduction in serum total cholesterol, triglyceride and low density lipoprotein levels. In conclusion, all three components of Triphala showed significant antidiabetic properties. T. bellirica, in addition, showed hypolipidemic activity.

scholarly journals Disruption of GIP/GIPR Axis in Human Adipose Tissue Is Linked to Obesity and Insulin Resistance

2014 ◽  
Vol 99 (5) ◽  
pp. E908-E919 ◽  
Author(s):  
Victòria Ceperuelo-Mallafré ◽  
Xavier Duran ◽  
Gisela Pachón ◽  
Kelly Roche ◽  
Lourdes Garrido-Sánchez ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Stem Cells ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Human Adipose Tissue ◽  
Fat Cells ◽  
Model Assessment ◽  
Adipose Derived Stem Cells ◽  
Obese Patients ◽  
Insulin Sensitizer

Context: Glucose-dependent insulinotropic peptide (GIP) has a central role in glucose homeostasis through its amplification of insulin secretion; however, its physiological role in adipose tissue is unclear. Objective: Our objective was to define the function of GIP in human adipose tissue in relation to obesity and insulin resistance. Design: GIP receptor (GIPR) expression was analyzed in human sc adipose tissue (SAT) and visceral adipose (VAT) from lean and obese subjects in 3 independent cohorts. GIPR expression was associated with anthropometric and biochemical variables. GIP responsiveness on insulin sensitivity was analyzed in human adipocyte cell lines in normoxic and hypoxic environments as well as in adipose-derived stem cells obtained from lean and obese patients. Results: GIPR expression was downregulated in SAT from obese patients and correlated negatively with body mass index, waist circumference, systolic blood pressure, and glucose and triglyceride levels. Furthermore, homeostasis model assessment of insulin resistance, glucose, and G protein-coupled receptor kinase 2 (GRK2) emerged as variables strongly associated with GIPR expression in SAT. Glucose uptake studies and insulin signaling in human adipocytes revealed GIP as an insulin-sensitizer incretin. Immunoprecipitation experiments suggested that GIP promotes the interaction of GRK2 with GIPR and decreases the association of GRK2 to insulin receptor substrate 1. These effects of GIP observed under normoxia were lost in human fat cells cultured in hypoxia. In support of this, GIP increased insulin sensitivity in human adipose-derived stem cells from lean patients. GIP also induced GIPR expression, which was concomitant with a downregulation of the incretin-degrading enzyme dipeptidyl peptidase 4. None of the physiological effects of GIP were detected in human fat cells obtained from an obese environment with reduced levels of GIPR. Conclusions: GIP/GIPR signaling is disrupted in insulin-resistant states, such as obesity, and normalizing this function might represent a potential therapy in the treatment of obesity-associated metabolic disorders.

scholarly journals Improvement of Liquid Fructose-Induced Adipose Tissue Insulin Resistance by Ginger Treatment in Rats Is Associated with Suppression of Adipose Macrophage-Related Proinflammatory Cytokines

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Jianwei Wang ◽  
Huanqing Gao ◽  
Dazhi Ke ◽  
Guowei Zuo ◽  
Yifan Yang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Proinflammatory Cytokines ◽  
Expression Profiles ◽  
Tolerance Test ◽  
Nonesterified Fatty Acid ◽  
Oral Glucose ◽  
Alcoholic Extract ◽  
Model Assessment ◽  
Necrosis Factor Alpha

Adipose tissue insulin resistance (Adipo-IR) results in excessive release of free fatty acids from adipose tissue, which plays a key role in the development of “lipotoxicity.” Therefore, amelioration of Adipo-IR may benefit the treatment of other metabolic abnormalities. Here we found that treatment with the alcoholic extract of ginger (50 mg/kg/day, by oral gavage) for five weeks attenuated liquid fructose-induced hyperinsulinemia and an increase in the homeostasis model assessment of insulin resistance (HOMA-IR) index in rats. More importantly, ginger reversed the increases in the Adipo-IR index and plasma nonesterified fatty acid concentrations during the oral glucose tolerance test assessment. Adipose gene/protein expression profiles revealed that ginger treatment suppressed CD68 and F4/80, two important macrophage accumulation markers. Consistently, the macrophage-associated cytokines tissue necrosis factor alpha and interleukin-6 were also downregulated. In contrast, insulin receptor substrate (IRS)-1, but not IRS-2, was upregulated. Moreover, monocyte chemotactic protein (MCP)-1 and its receptor chemokine (C-C motif) receptor-2 were also suppressed. Thus these results suggest that amelioration of fructose-induced Adipo-IR by ginger treatment in rats is associated with suppression of adipose macrophage-related proinflammatory cytokines.

Follistatin-like 1 as a Novel Adipomyokine Related to Insulin Resistance and Physical Activity

2020 ◽  
Vol 105 (12) ◽  
pp. e4499-e4509 ◽  
Author(s):  
Xiaohui Xu ◽  
Tingran Zhang ◽  
Mani Mokou ◽  
Ling Li ◽  
Peng Li ◽  
...  
Keyword(s):  
Physical Activity ◽  
Insulin Resistance ◽  
Adipose Tissue ◽  
Protein Expression ◽  
Cold Exposure ◽  
Enzyme Linked Immunosorbent Assay ◽  
Oral Glucose ◽  
Exposure Test ◽  
Western Blots ◽  
Lipid Infusion

Abstract Background and Aims Follistatin-like protein-1 (FSTL-1) is considered to be an adipokine or myokine that could be a potential regulator of metabolism. Our purpose is to investigate the relationship between circulating FSTL-1 levels and insulin resistance (IR) in type 2 diabetes mellitus (T2DM) and to identify the regulatory factors. Methods FSTL-1 expression in C57BL/6J and db/db mice was examined by quantitative reverse transcriptase–polymerase chain reaction (qRT-PCR) and Western blots. Serum FSTL-1 levels were measured by enzyme-linked immunosorbent assay in 298 T2DM patients and 202 healthy controls. Changes in the circulating FSTL-1 level were observed during the oral glucose tolerance test, EHC (euglycemic-hyperinsulinemic clamp), lipid infusion, acute exercise, and cold-exposure test. Results We found that FSTL-1 protein expression in the adipose tissue of db/db mice was significantly higher than that of wild-type mice. Importantly, circulating FSTL-1 levels in T2DM and overweight/obese participants were higher than those in healthy and lean individuals, and was related to HOMA-IR, adiponectin, and obesity- and metabolism-related parameters. In the intervention study, 45 minutes of physical activity was found to significantly increase the circulating FSTL-1 concentration in young, healthy participants. Further, FSTL-1 protein expression in adipose tissue rose dramatically in response to physical activity in mice. Hyperinsulinemia during EHC and acute elevated FFA induced by lipid infusion resulted in a significant decrease in the circulating FSTL-1 levels. However, no change was found in the circulating FSTL-1 levels in response to the oral glucose challenge or cold-exposure test. Conclusions FSTL-1 may be an adipomyokine associated with insulin resistance and physical activity, and circulating FSTL-1 levels are increased in patients with T2DM.

scholarly journals Comparison of Frequency and Severity of Sleep-Related Breathing Disorders in Children with Simple Obesity and Paediatric Patients with Prader–Willi Syndrome

2021 ◽  
Vol 11 (2) ◽  
pp. 141
Author(s):  
Agnieszka Lecka-Ambroziak ◽  
Marta Wysocka-Mincewicz ◽  
Anna Świercz ◽  
Małgorzata Jędrzejczak ◽  
Mieczysław Szalecki
Keyword(s):  
Insulin Resistance ◽  
Apnea Hypopnea Index ◽  
Oral Glucose ◽  
Prader Willi Syndrome ◽  
Model Assessment ◽  
Sleep Related Breathing Disorders ◽  
Breathing Disorders ◽  
Simple Obesity ◽  
Rhgh Treatment ◽  
Group 1

Sleep-related breathing disorders (SRBDs) can be present in children with simple obesity and with Prader–Willi syndrome (PWS) and influence an individual diagnostic and treatment approach. We compared frequency and severity of SRBDs in children with simple obesity and with PWS, both without and on recombinant human growth hormone (rhGH) treatment, and correlation of SRBDs with insulin resistance tests. A screening polysomnography-polygraphy (PSG), the oral glucose tolerance test (OGTT) and homeostasis model assessment of insulin resistance (HOMA-IR) were analysed in three groups of patients—with simple obesity (group 1, n = 30, mean age 14.2 years), patients with PWS without the rhGH therapy (group 2, n = 8, mean age 13.0 years) and during the rhGH treatment (group 3, n = 17, mean age 8.9 years). The oxygen desaturation index (ODI) was significantly higher in groups 2 and 3, compared to group 1 (p = 0.00), and hypopnea index (HI) was higher in group 1 (p = 0.03). Apnea–hypopnea index (AHI) and apnea index (AI) results positively correlated with the insulin resistance parameters in groups 1 and 3. The PSG values worsened along with the increasing insulin resistance in children with simple obesity and patients with PWS treated with rhGH that may lead to a change in the patients’ care.

Investigating the relationship between insulin resistance and adipose tissue in a randomized Tehrani population

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Jalaledin Mirzay Razzaz ◽  
Hossein Moameri ◽  
Zahra Akbarzadeh ◽  
Mohammad Ariya ◽  
Seyed ali Hosseini ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Body Fat ◽  
Odds Ratio ◽  
Cross Sectional Study ◽  
Model Assessment ◽  
Fasting Insulin ◽  
Cross Sectional ◽  
Body Fat Percent ◽  
The Relationship

Abstract Objectives Insulin resistance is the most common metabolic change associated with obesity. The present study aimed to investigate the relationship between insulin resistance and body composition especially adipose tissue in a randomized Tehrani population. Methods This study used data of 2,160 individuals registered in a cross-sectional study on were randomly selected from among subjects who were referred to nutrition counseling clinic in Tehran, from April 2016 to September 2017. Insulin resistance was calculated by homeostasis model assessment formula. The odds ratio (95% CI) was calculated using logistic regression models. Results The mean age of the men was 39 (±10) and women were 41 (±11) (the age ranged from 20 to 50 years). The risk of increased HOMA-IR was 1.03 (95% CI: 1.01–1.04) for an increase in one percent of Body fat, and 1.03 (95% CI: 1.00–1.05) for an increase in one percent of Trunk fat. Moreover, the odds ratio of FBS for an increase in one unit of Body fat percent and Trunk fat percent increased by 1.05 (adjusted odds ratio [95% CI: 1.03, 1.06]) and 1.05 (95% CI: 1.02, 1.08). Also, the risk of increased Fasting Insulin was 1.05 (95% CI: 1.03–1.07) for an increase in one unit of Body fat percent, and 1.05 (95% CI: 1.02–1.08) for an increase in one unit of Trunk fat percent. Conclusions The findings of the present study showed that there was a significant relationship between HOMA-IR, Fasting blood sugar, Fasting Insulin, and 2 h Insulin with percent of Body fat, percent of Trunk fat.

scholarly journals Plasma resistin, adiponectin and leptin levels in lean and obese subjects: correlations with insulin resistance

2003 ◽  
Vol 149 (4) ◽  
pp. 331-335 ◽  
Author(s):  
JV Silha ◽  
M Krsek ◽  
JV Skrha ◽  
P Sucharda ◽  
BL Nyomba ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Mass Index ◽  
Adipose Tissue ◽  
Statistical Significance ◽  
Model Assessment ◽  
Fasting Insulin ◽  
Homeostasis Model Assessment ◽  
Glucose Levels ◽  
Obese Subjects ◽  
The Relationship

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.

scholarly journals The Relationship between Insulin Resistance and the Cardiovascular Biomarker Growth Differentiation Factor-15 in Obese Patients

2011 ◽  
Vol 57 (2) ◽  
pp. 309-316 ◽  
Author(s):  
Greisa Vila ◽  
Michaela Riedl ◽  
Christian Anderwald ◽  
Michael Resl ◽  
Ammon Handisurya ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Gastric Bypass ◽  
Insulin Sensitivity ◽  
Oral Glucose ◽  
Model Assessment ◽  
Obese Patients ◽  
Growth Differentiation Factor 15 ◽  
Homeostatic Model Assessment ◽  
Homeostatic Model ◽  
The Relationship

BACKGROUND Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine linked to obesity comorbidities such as cardiovascular disease, inflammation, and cancer. GDF-15 also has adipokine properties and recently emerged as a prognostic biomarker for cardiovascular events. METHODS We evaluated the relationship of plasma GDF-15 concentrations with parameters of obesity, inflammation, and glucose and lipid metabolism in a cohort of 118 morbidly obese patients [mean (SD) age 37.2 (12) years, 89 females, 29 males] and 30 age- and sex-matched healthy lean individuals. All study participants underwent a 75-g oral glucose tolerance test; 28 patients were studied before and 1 year after Roux-en-Y gastric bypass surgery. RESULTS Obese individuals displayed increased plasma GDF-15 concentrations (P &lt; 0.001), with highest concentrations observed in patients with type 2 diabetes. GDF-15 was positively correlated with age, waist-to-height ratio, mean arterial blood pressure, triglycerides, creatinine, glucose, insulin, C-peptide, hemoglobin A1c, and homeostatic model assessment insulin resistance index and negatively correlated with oral glucose insulin sensitivity. Age, homeostatic model assessment index, oral glucose insulin sensitivity, and creatinine were independent predictors of GDF-15 concentrations. Roux-en-Y gastric bypass led to a significant reduction in weight, leptin, insulin, and insulin resistance, but further increased GDF-15 concentrations (P &lt; 0.001). CONCLUSIONS The associations between circulating GDF-15 concentrations and age, insulin resistance, and creatinine might account for the additional cardiovascular predictive information of GDF-15 compared to traditional risk factors. Nevertheless, GDF-15 changes following bariatric surgery suggest an indirect relationship between GDF-15 and insulin resistance. The clinical utility of GDF-15 as a biomarker might be limited until the pathways directly controlling GDF-15 concentrations are better understood.

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