Abstract
BackgroundThe 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.MethodsIn 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.ResultsThe 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.ConclusionsComprehensive metabolic profiling supports that MHO subjects have intermediate-stage cardiovascular disease risk marker profile compared with NW and MUO subjects.Clinical trial registration numberNCT01034436, Fatty acid quality and overweight (FO-study).Graphical abstract
Highlights
The ever-increasing prevalence of obesity constitutes a major health problem worldwide
Principal component analysis First, we analyzed the variability among the groups using principal component analyses (PCA) by either clinical data, different metabolites, as well as plasma fatty acid composition and dietary intake (Additional file 1)
The three groups were fairly well separated for the two former data types; metabolically unhealthy obese (MUO) and metabolically healthy obese” (MHO) groups were well separated by fatty acids but not by dietary intake
Summary
The ever-increasing prevalence of obesity constitutes a major health problem worldwide. In contrast to metabolically unhealthy obese (MUO), the MHO phenotype has a favorable risk profile. Our aim was to increase the understanding of metabolic alterations associated with healthy and unhealthy obesity. Even though individuals with MHO will shift towards an MUO profile with time, a more profound understanding of the underlying metabolic regulation in MHO and MUO is necessary to enhance our understanding of the development of metabolic dysfunction associated with obesity, and how to prevent it with lifestyle changes. Differences between subgroups of individuals with obesity, like MHO and MUO, are less investigated. A detailed study of lipoprotein metabolism and the detection of subtle differences in the distribution of lipoproteins between MHO and MUO may increase our understanding of the lipid metabolism in obesity, to target prevention and treatment more precisely among MUO and MHO
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