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A comprehensive metabolic profiling of the metabolically healthy obesity phenotype.

ABSTRACT: BACKGROUND:The ever-increasing prevalence of obesity constitutes a major health problem worldwide. A subgroup of obese individuals has been described as "metabolically healthy obese" (MHO). In contrast to metabolically unhealthy obese (MUO), the MHO phenotype has a favorable risk profile. Despite this, the MHO phenotype is still sub-optimally characterized with respect to a comprehensive risk assessment. Our aim was to increase the understanding of metabolic alterations associated with healthy and unhealthy obesity. METHODS:In this cross-sectional study, men and women (18-70?years) with obesity (body mass index (BMI)???30?kg/m2) or normal weight (NW) (BMI???25?kg/m2) were classified with MHO (n?=?9), MUO (n?=?10) or NW (n?=?11) according to weight, lipid profile and glycemic regulation. We characterized individuals by comprehensive metabolic profiling using a commercial available high-throughput proton NMR metabolomics platform. Plasma fatty acid profile, including short chain fatty acids, was measured using gas chromatography. RESULTS:The concentrations of very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and low density lipoprotein (LDL) subclasses were overall significantly higher, and high density lipoprotein (HDL) subclasses lower in MUO compared with MHO. VLDL and IDL subclasses were significantly lower and HDL subclasses were higher in NW compared with MHO. The concentration of isoleucine, leucine and valine was significantly higher in MUO compared with MHO, and the concentration phenylalanine was lower in NW subjects compared with MHO. The fatty acid profile in MHO was overall more favorable compared with MUO. CONCLUSIONS:Comprehensive metabolic profiling supports that MHO subjects have intermediate-stage cardiovascular disease risk marker profile compared with NW and MUO subjects. CLINICAL TRIAL REGISTRATION NUMBER:NCT01034436, Fatty acid quality and overweight (FO-study).

SUBMITTER: Telle-Hansen VH

PROVIDER: S-EPMC7211343 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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A comprehensive metabolic profiling of the metabolically healthy obesity phenotype.

Telle-Hansen Vibeke H VH Christensen Jacob J JJ Formo Gulla Aase GA Holven Kirsten B KB Ulven Stine M SM

Lipids in health and disease 20200509 1

<h4>Background</h4>The ever-increasing prevalence of obesity constitutes a major health problem worldwide. A subgroup of obese individuals has been described as "metabolically healthy obese" (MHO). In contrast to metabolically unhealthy obese (MUO), the MHO phenotype has a favorable risk profile. Despite this, the MHO phenotype is still sub-optimally characterized with respect to a comprehensive risk assessment. Our aim was to increase the understanding of metabolic alterations associated with h ...[more]

PMID: 32386512

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Project description:Obesity and obesity-related low-grade inflammation are common findings in polycystic ovary syndrome (PCOS), the most common endocrine-metabolic disorder-affecting women in reproductive age. The terms metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO) have been introduced to define individuals with obesity in whom cardio-metabolic risk factors are absent or present, respectively. To date, evidence investigating differences in body composition and adherence to the Mediterranean diet (MD) between MHO and MUO-PCOS women are lacking. Aim of this study was to better characterize the determinants of the metabolic health status in PCOS patients with obesity according to MHO and MUO phenotypes by evaluating endocrine-metabolic profile, inflammatory status, adherence to the MD, and body composition. The study population consisted of 94 treatment-naïve women with PCOS and obesity (BMI = 38.23 ± 6.62 kg/m2 and age = 24.12 ± 3.68 years). Compared PCOS MHO with PCOS MUO patients, the latter had higher levels of high-sensitivity C-reactive protein (hs-CRP) (p < 0.001), testosterone (p < 0.001), and insulin (p < 0.001), worse metabolic parameters, and higher Homeostatic Model Assessment of Insulin Resistance (HoMA-IR), Visceral Adiposity Index (VAI), and Fatty liver Index (FLI) (p < 0.001). Furthermore, PCOS MUO patients had lower adherence to the MD (p < 0.001) in spite of the same total energy intake (p = 0.102) as compared to PCOS MHO. The presence of MUO was associated with highest hs-CRP levels (OR = 1.49, p < 0.001), more severe hyperandrogenism and cardio-metabolic indices (p < 0.001). On the contrary, being PCOS MUO was associated with lower adherence to the MD (OR = 0.28, p < 0.001), and smaller PhAs (OR = 0.04, p < 0.001). Using a regression linear analysis model PREDIMED score entered at the first step (p < 0.001), followed by VAI (p < 0.001), and FLI (p = 0.032) in this analysis. At ROC analysis, a PREDIMED score of ≤4 (p < 0.001, AUC 0.926) could serve as a threshold for a significantly increased risk of presence the MUO-PCOS phenotype. To the best of our knowledge, this is the first study that characterized MHO and MUO-PCOS women on the basis of their adherence to the MD, body composition, and cardio-metabolic indices, providing evidence of the usefulness of adjunctive diagnostic parameters to better differentiate the MHO/MHO phenotypes in this cohort of PCOS patients with obesity.

Project description:Inflammation occurs as an immediate protective response of the immune system to a harmful stimulus, whether locally confined or systemic. In contrast, a persisting, i.e., chronic, inflammatory state, even at a low-grade, is a well-known risk factor in the development of common diseases like diabetes or atherosclerosis. In clinical practice, laboratory markers like high-sensitivity C-reactive protein (hsCRP), white blood cell count (WBC), and fibrinogen, are used to reveal inflammatory processes. In order to gain a deeper insight regarding inflammation-related changes in metabolism, the present study assessed the metabolic patterns associated with alterations in inflammatory markers.Based on mass spectrometry and nuclear magnetic resonance spectroscopy we determined a comprehensive panel of 613 plasma and 587 urine metabolites among 925 apparently healthy individuals. Associations between inflammatory markers, namely hsCRP, WBC, and fibrinogen, and metabolite levels were tested by linear regression analyses controlling for common confounders. Additionally, we tested for a discriminative signature of an advanced inflammatory state using random forest analysis.HsCRP, WBC, and fibrinogen were significantly associated with 71, 20, and 19 plasma and 22, 3, and 16 urine metabolites, respectively. Identified metabolites were related to the bradykinin system, involved in oxidative stress (e.g., glutamine or pipecolate) or linked to the urea cycle (e.g., ornithine or citrulline). In particular, urine 3'-sialyllactose was found as a novel metabolite related to inflammation. Prediction of an advanced inflammatory state based solely on 10 metabolites was well feasible (median AUC: 0.83).Comprehensive metabolic profiling confirmed the far-reaching impact of inflammatory processes on human metabolism. The identified metabolites included not only those already described as immune-modulatory but also completely novel patterns. Moreover, the observed alterations provide molecular links to inflammation-associated diseases like diabetes or cardiovascular disorders.

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A comprehensive metabolic profiling of the metabolically healthy obesity phenotype.

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A comprehensive metabolic profiling of the metabolically healthy obesity phenotype.

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