title: Proteomics reveals the effects of sustained weight loss on the human plasma proteome.
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.
authors.affiliation: Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.|NNF Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Philipp E
authors.initials: PE
authors.lastname: Geyer
authors.affiliation: NNF Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.|Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.|NNF Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Nicolai J
authors.initials: NJ
authors.lastname: Wewer Albrechtsen
authors.affiliation: Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: Stefka
authors.initials: S
authors.lastname: Tyanova
authors.affiliation: Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: Niklas
authors.initials: N
authors.lastname: Grassl
authors.affiliation: Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.|NNF Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Eva W
authors.initials: EW
authors.lastname: Iepsen
authors.affiliation: Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.|NNF Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Julie
authors.initials: J
authors.lastname: Lundgren
authors.affiliation: NNF Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.|Department of Endocrinology, Hvidovre University Hospital, Hvidovre, Denmark.
authors.forename: Sten
authors.initials: S
authors.lastname: Madsbad
authors.affiliation: Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.|NNF Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.affiliation: Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.|NNF Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Signe S
authors.initials: SS
authors.lastname: Torekov
authors.affiliation: Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany mmann@biochem.mpg.de.|NNF Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Matthias
authors.identifier: http://orcid.org/0000-0003-1292-4799
authors.initials: M
authors.lastname: Mann
mesh_terms: D000328:Adult; D001053:Apolipoproteins / Q000097:blood; D031204:Caloric Restriction; D005136:Eye Proteins / Q000097:blood; D005786:Gene Expression Regulation; D006801:Humans; D007333:Insulin Resistance; D008137:Longitudinal Studies; D013058:Mass Spectrometry / Q000379:methods*; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000097:blood; D009765:Obesity / Q000178:diet therapy* / Q000378:metabolism; D010949:Plasma / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D015843:Serpins / Q000097:blood; D015431:Weight Loss; D055815:Young Adult; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D001053:Apolipoproteins; D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor
keywords: diabetes; mass spectrometry; metabolic syndrome; obesity; plasma proteome profiling