Proinflammatory and lipid biomarkers mediate metabolically healthy obesity: A proteomics study.
The metabolically healthy obesity (MHO) phenotype is an important obesity subtype in which obesity is not accompanied by any metabolic comorbidity. However, the underlying molecular mechanisms remain elusive. In this study, a shotgun proteomics approach to identify circulating biomolecules and pathways associated with MHO was used.



The subjects were 20 African-American women: 10 MHO cases and 10 metabolically abnormal individuals with obesity (MAO) controls. Serum proteins were detected and quantified using label-free proteomics. Differential expression of proteins between the two groups was analyzed, and the list of differentially expressed proteins was analyzed to determine enriched biological pathways.



Twenty proteins were differentially expressed between MHO and controls. These proteins included: hemoglobin subunits (HBA1, P = 6.00 × 10(-18) ), haptoglobin-related protein (HPR, P = 1.2 × 10(-15) ), apolipoproteins (APOB-100, P = 1.50 × 10(-40) ; APOA4, P = 1.1 × 10(-14) ), retinol-binding protein 4 (RBP4, P = 7.1 × 10(-08) ), and CRP (P = 2.0 × 10(-04) ). MHO was associated with lower levels of proinflammatory and higher levels of anti-inflammatory biomarkers when compared with MAO. Pathway analysis showed enrichment of lipids and inflammatory pathways, including LXR/RXR and FXR/RXR activation, and acute phase response signaling.



These findings suggested that protection from dysregulated inflammatory and lipid processes were primary molecular hallmarks of MHO. The candidate biomarkers (AHSG, RBP4, and APOA4) identified in this study are potential prognostic markers for MHO.
Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
Ayo Priscille
AP
Doumatey
Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
Jie
J
Zhou
Laboratory of Proteomics and Analytical Technologies (LPAT) Leidos Biomedical Research Inc, National Cancer Institute, National Institutes of Health, Frederick, Maryland, USA.
Ming
M
Zhou
Laboratory of Proteomics and Analytical Technologies (LPAT) Leidos Biomedical Research Inc, National Cancer Institute, National Institutes of Health, Frederick, Maryland, USA.
DaRue
D
Prieto
Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
Charles N
CN
Rotimi
Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
Adebowale
A
Adeyemo
D000328:Adult; D001741:Black or African American; D053299:Apolipoprotein B-100 / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D015992:Body Mass Index; D016022:Case-Control Studies; D005260:Female; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000378:metabolism*; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism; D000067329:Obesity, Metabolically Benign / Q000150:complications / Q000378:metabolism*; D010641:Phenotype; D040901:Proteomics
C569471:APOB protein, human; D053299:Apolipoprotein B-100; D015415:Biomarkers; D008055:Lipids; D006710:Homocysteine