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Metabolomics Reveals Metabolically Healthy and Unhealthy Obese Individuals Differ in their Response to a Caloric Challenge.

ABSTRACT: OBJECTIVE:To determine if metabolically healthy obese (MHO) individuals have a different metabolic response to a standardized diet compared to lean healthy (LH) and metabolically unhealthy obese (MUO) individuals. METHODS:Thirty adults (35-70 yrs) were classified as LH, MHO, and MUO according to anthropometric and clinical measurements. Participants consumed a standardized high calorie meal (~1330 kcal). Blood glucose and insulin were measured at fasting, and 15, 30, 60, 90 and 120 min postprandially. Additional blood samples were collected for the targeted analysis of amino acids (AAs) and derivatives, and fatty acids (FAs). RESULTS:The postprandial response (i.e., area under the curve, AUC) for serum glucose and insulin were similar between MHO and LH individuals, and significantly lower than MUO individuals (p < 0.05). Minor differences were found in postprandial responses for AAs between MHO and MUO individuals, while three polyunsaturated FAs (linoleic acid, ?-linolenic acid, arachidonic acid) showed smaller changes in serum after the meal in MHO individuals compared to MUO. Fasting levels for various AAs (notably branched-chain AA) and FAs (e.g., saturated myristic and palmitic acids) were found to correlate with glucose and insulin AUC. CONCLUSION:MHO individuals show preserved insulin sensitivity and a greater ability to adapt to a caloric challenge compared to MUO individuals.

SUBMITTER: Badoud F

PROVIDER: S-EPMC4537251 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Metabolomics Reveals Metabolically Healthy and Unhealthy Obese Individuals Differ in their Response to a Caloric Challenge.

Badoud Flavia F Lam Karen P KP Perreault Maude M Zulyniak Michael A MA Britz-McKibbin Philip P Mutch David M DM

PloS one 20150814 8

<h4>Objective</h4>To determine if metabolically healthy obese (MHO) individuals have a different metabolic response to a standardized diet compared to lean healthy (LH) and metabolically unhealthy obese (MUO) individuals.<h4>Methods</h4>Thirty adults (35-70 yrs) were classified as LH, MHO, and MUO according to anthropometric and clinical measurements. Participants consumed a standardized high calorie meal (~1330 kcal). Blood glucose and insulin were measured at fasting, and 15, 30, 60, 90 and 12 ...[more]

PMID: 26274804

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Project description:BackgroundObesity is associated with severe co-morbidities such as type 2 diabetes and nonalcoholic steatohepatitis. However, studies have shown that 10-25 percent of the severely obese individuals are metabolically healthy. To date, the identification of genetic factors underlying the metabolically healthy obese (MHO) state is limited. Systems genetics approaches have led to the identification of genes and pathways in complex diseases. Here, we have used such approaches across tissues to detect genes and pathways involved in obesity-induced disease development.MethodsExpression data of 60 severely obese individuals was accessible, of which 28 individuals were MHO and 32 were metabolically unhealthy obese (MUO). A whole genome expression profile of four tissues was available: liver, muscle, subcutaneous adipose tissue and visceral adipose tissue. Using insulin-related genes, we used the weighted gene co-expression network analysis (WGCNA) method to build within- and inter-tissue gene networks. We identified genes that were differentially connected between MHO and MUO individuals, which were further investigated by homing in on the modules they were active in. To identify potentially causal genes, we integrated genomic and transcriptomic data using an eQTL mapping approach.ResultsBoth IL-6 and IL1B were identified as highly differentially co-expressed genes across tissues between MHO and MUO individuals, showing their potential role in obesity-induced disease development. WGCNA showed that those genes were clustering together within tissues, and further analysis showed different co-expression patterns between MHO and MUO subnetworks. A potential causal role for metabolic differences under similar obesity state was detected for PTPRE, IL-6R and SLC6A5.ConclusionsWe used a novel integrative approach by integration of co-expression networks across tissues to elucidate genetic factors related to obesity-induced metabolic disease development. The identified genes and their interactions give more insight into the genetic architecture of obesity and the association with co-morbidities.

Dataset Information

Metabolomics Reveals Metabolically Healthy and Unhealthy Obese Individuals Differ in their Response to a Caloric Challenge.

Publications

Metabolomics Reveals Metabolically Healthy and Unhealthy Obese Individuals Differ in their Response to a Caloric Challenge.

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