Abstract
Sustained weight loss is a preferred intervention in a wide range of metabolic conditions, but the effects on an individual's health state remain ill‐defined. Here, we investigate the plasma proteomes of a cohort of 43 obese individuals that had undergone 8 weeks of 12% body weight loss followed by a year of weight maintenance. Using mass spectrometry‐based plasma proteome profiling, we measured 1,294 plasma proteomes. Longitudinal monitoring of the cohort revealed individual‐specific protein levels with wide‐ranging effects of losing weight on the plasma proteome reflected in 93 significantly affected proteins. The adipocyte‐secreted SERPINF1 and apolipoprotein APOF1 were most significantly regulated with fold changes of −16% and +37%, respectively (P < 10−13), and the entire apolipoprotein family showed characteristic differential regulation. Clinical laboratory parameters are reflected in the plasma proteome, and eight plasma proteins correlated better with insulin resistance than the known marker adiponectin. Nearly all study participants benefited from weight loss regarding a ten‐protein inflammation panel defined from the proteomics data. We conclude that plasma proteome profiling broadly evaluates and monitors intervention in metabolic diseases.
Highlights
Obesity and the metabolic syndrome represent a major public health burden, predisposing to several diseases including type 2 diabetes and cardiovascular syndromes and increasing the overall likelihood of early death (Eckel et al, 2005; Grundy, 2015)
The metabolic state is reflected in the levels of lipid transport proteins in the blood, most prominently the apolipoprotein family that is involved in lipid turnover
We recently described a highly sensitive proteomics sample preparation method that can be performed with a minimum number of steps in a single reaction vial (Kulak et al, 2014)
Summary
Obesity and the metabolic syndrome represent a major public health burden, predisposing to several diseases including type 2 diabetes and cardiovascular syndromes and increasing the overall likelihood of early death (Eckel et al, 2005; Grundy, 2015). The chances of developing the metabolic syndrome can be reduced considerably by sustained weight loss in obese individuals, through its positive effects on a broad range of metabolic risk factors (Hansen & Bray, 2008). Obesity is associated with increased systemic low-grade inflammation, as indicated by plasma levels of specific markers such as C-reactive protein (Esser et al, 2014). These proteins are normally quantified individually by antibody-based assays, providing only a partial picture of changes in the entirety of proteins in this body fluid, the plasma proteome. In the case of weight loss, particular proteins like sex hormone-binding globulin are known to change (Azrad et al, 2012), but a global view of the dynamic changes in the plasma proteome is currently lacking
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