Proteomics reveals the effects of sustained weight loss on the human plasma proteome

TY - JOUR

T1 - Proteomics reveals the effects of sustained weight loss on the human plasma proteome

AU - Geyer, Philipp E

AU - Wewer Albrechtsen, Nicolai J

AU - Tyanova, Stefka

AU - Grassl, Niklas

AU - Iepsen, Eva Pers Winning

AU - Lundgren, Julie

AU - Madsbad, Sten

AU - Holst, Jens J

AU - Torekov, Signe S

AU - Mann, Matthias

N1 - © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

PY - 2016/12/1

Y1 - 2016/12/1

N2 - 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.

AB - 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.

U2 - 10.15252/msb.20167357

DO - 10.15252/msb.20167357

M3 - Journal article

C2 - 28007936

SN - 1744-4292

VL - 12

JO - Molecular Systems Biology

JF - Molecular Systems Biology

M1 - 901

ER -