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A distinct fatty acid profile underlies the reduced inflammatory state of metabolically healthy obese individuals.

ABSTRACT: Obesity is associated with numerous health complications; however, a subgroup of obese individuals (termed the metabolically healthy obese or MHO) appear to have lower risk for complications such as type 2 diabetes and cardiovascular disease. Emerging evidence suggests that MHO individuals have reduced inflammation compared to their metabolically unhealthy obese (MUO) counterparts. As it is recognized that fatty acids (FAs) have a strong relationship with inflammation, the current study aimed to uncover if the reduced inflammation observed in MHO individuals is mirrored by a more favourable FA profile.Fasted serum samples were collected from lean healthy (LH), MHO, and MUO participants (n = 10/group) recruited from the Diabetes Risk Assessment study. A panel of pro- and anti-inflammatory markers were measured by immunoassay. Total serum FA profiling, as well as the FA composition of circulating phospholipids (PL) and triglycerides (TG), was measured by gas chromatography. ANOVA and Mann-Whitney-Wilcoxon tests were used to assess statistical significance between the groups (P<0.05).MHO and MUO individuals had similar BMI and body fat %; however, lipid parameters in MHO individuals more closely resembled that of LH individuals. MHO individuals had circulating levels of high sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) similar to LH individuals, while levels of platelet derived growth factor-?? (PDGF-??) were intermediate to that of LH and MUO individuals. FA profiling analysis combined with discriminant analysis modelling highlighted a panel of nine FAs (consisting of three saturated, three monounsaturated, and three polyunsaturated FAs) in PL and TG fractions that distinguished the three groups. Specifically, saturated FA (myristic and stearic acids) levels in MHO individuals resembled that of LH individuals.Our results suggest that the reduced inflammatory state of MHO individuals compared to MUO individuals may stem, in part, from a more favourable underlying FA profile.

SUBMITTER: Perreault M

PROVIDER: S-EPMC3919777 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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A distinct fatty acid profile underlies the reduced inflammatory state of metabolically healthy obese individuals.

Perreault Maude M Zulyniak Michael A MA Badoud Flavia F Stephenson Susan S Badawi Alaa A Buchholz Andrea A Mutch David M DM

PloS one 20140210 2

<h4>Background</h4>Obesity is associated with numerous health complications; however, a subgroup of obese individuals (termed the metabolically healthy obese or MHO) appear to have lower risk for complications such as type 2 diabetes and cardiovascular disease. Emerging evidence suggests that MHO individuals have reduced inflammation compared to their metabolically unhealthy obese (MUO) counterparts. As it is recognized that fatty acids (FAs) have a strong relationship with inflammation, the cur ...[more]

PMID: 24520395

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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.

Project description:ObjectivesThis study aimed to compare serum free fatty acids (FFAs) and lipopolysaccharide-binding protein (LBP) between metabolically healthy abdominally obese (MHAO) and metabolically unhealthy abdominally obese (MUAO) individuals. We also examined the association between serum FFAs and LBP in the participants.MethodsIn this age-matched and gender-matched case-control study, 164 abdominally obese subjects were recruited from June to November 2015 in the northwest of Iran. Demographic data, dietary intake, body composition, anthropometric indices and physical activity (PA) were assessed. Basal blood samples were collected to determine serum metabolic parameters, FFAs and LBP. Abdominal obesity was defined as having waist circumference ?95?cm. Those with three or more metabolic alterations were defined as MUAO and those having two or less were classified as MHAO. Data were analysed using SPSS V.17.0.ResultsThere were no significant differences in dietary intake, anthropometric indices, body composition and PA between the two groups. The odds of MUAO significantly increased by increments in serum fasting blood sugar (OR 3.79, 95% CI 2.25 to 6.40), triglycerides (OR 1.10, 95% CI 1.05 to 1.15), systolic blood pressure (OR 1.02, 95% CI 1.00 to 1.04) and diastolic blood pressure (OR 1.03, 95% CI 1.01 to 1.06) and decreased by increase in serum high-density lipoprotein cholesterol (OR 0.32, 95% CI 0.20 to 0.52). The levels of LBP and FFAs showed no significant differences between the two groups. However, significant correlations were found between LBP and FFAs in pooled population (r=0.712; p<0.001) as well as in cases (r=0.717; p<0.001) and controls (r=0.704; p<0.001). Neither FFAs nor LBP were significantly correlated with dietary intake or metabolic parameters (p>0.05).ConclusionThe results indicated that serum LBP and FFAs are highly correlated both in MHAO and MUAO states. In addition, the levels of LBP and FFAs seem to be more related to abdominal obesity than to the presence or absence of metabolic health.

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A distinct fatty acid profile underlies the reduced inflammatory state of metabolically healthy obese individuals.

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A distinct fatty acid profile underlies the reduced inflammatory state of metabolically healthy obese individuals.

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