Abstract
Method Associations between different biomarkers (proteomics, lipidomics, and metabolomics) coupled to either MHO or metabolically unhealthy obese (MUO) individuals were analyzed through principal component analysis (PCA). Subjects were identified from a subsample of 416 obese individuals, selected from the Malmö Diet and Cancer study—Cardiovascular arm (MDCS-CV, n = 3,443). They were further divided into MHO (n = 143) and MUO (n = 273) defined by a history of hospitalization, or not, at baseline inclusion, and nonobese subjects (NOC, n = 3,027). Two distinctive principle components (PL2, PP5) were discovered with a significant difference and thus further investigated through their main loadings. Results MHO individuals had a more metabolically favorable lipid and glucose profile than MUO subjects, that is, lower levels of traditional blood glucose and triglycerides, as well as a trend of lower metabolically unfavorable lipid biomarkers. PL2 (lipidomics, p=0.02) showed stronger associations of triacylglycerides with MUO, whereas phospholipids correlated with MHO. PP5 (proteomics, p=0.01) included interleukin-1 receptor antagonist (IL-1ra) and leptin with positive relations to MUO and galanin that correlated positively to MHO. The group differences in metabolite profiles were to a large extent explained by factors included in the metabolic syndrome. Conclusion Compared to MUO individuals, corresponding MHO individuals present with a more favorable lipid metabolic profile, accompanied by a downregulation of potentially harmful proteomic biomarkers. This unique and extensive biomarker profiling presents novel data on potentially differentiating traits between these two obese phenotypes.
Highlights
Obesity is a well-established risk factor for the development of endemic modern Western public health problems, including cardiovascular disease (CVD) and type 2 diabetes (DM2) [1], accumulating evidence is suggesting that there is a small proportion of individuals with excess weight (body mass index (BMI) ≥ 30 kg/m2) that seem to escape these aforementioned conditions—a concept known as Metabolically Healthy Obesity (MHO) [2, 3]
In a recent paper [9], we defined MHO as obese individuals (BMI ≥ 30 kg/m2) who had never been hospitalized for a somatic disease before study baseline and described the prognosis regarding incident CVD and mortality risk of MHO subjects compared to Metabolically Unhealthy Obesity (MUO) and nonobese controls (NOC) in a Swedish cohort from the 1990s—the Malmo Diet and Cancer Study (MDCS; n 28,098)
Our findings suggested that MHO individuals had a significantly lower risk of total mortality and developing CVD during a 20-year follow-up period, compared to MUO individuals
Summary
Obesity is a well-established risk factor for the development of endemic modern Western public health problems, including cardiovascular disease (CVD) and type 2 diabetes (DM2) [1], accumulating evidence is suggesting that there is a small proportion of individuals with excess weight (body mass index (BMI) ≥ 30 kg/m2) that seem to escape these aforementioned conditions—a concept known as Metabolically Healthy Obesity (MHO) [2, 3] Along with this phenomenon, there has been a debate concerning the heterogeneity of obesity, and the negative consequences of excess fat seem to be more complex and individually patterned than previously thought [2, 4]. Descriptive data from the study showed that MHO individuals presented with a less sedentary lifestyle, held a higher educational level, and displayed a more favorable glucose and lipid blood profile [9]. ese descriptive findings were in line with earlier publications [10, 11], our definition of MHO was novel and differed from previous ones [9]
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