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/ m 2) or normal weight (NW) (BMI ≤ 25 kg/m 2) 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).

Our cells use the food we eat to produce the energy needed to do work. This amazing process is called metabolism and it is necessary for survival. If we eat more than we need, we will gain weight and may become obese. Obesity affects how cells and organs perform work and also increases the risk of metabolic diseases, which include type 2 diabetes and cardiovascular diseases. Metabolic diseases are the most common diseases of our time. National and global health authorities are working hard to prevent and treat obesity and obesity-related diseases. However, some people with obesity appear to have normal metabolism. Why do some obese people develop metabolic diseases while others do not? In this article, we discuss how metabolism may differ in people with obesity. We also describe some key reasons why some people with obesity may be healthier than others.