title: Mature adipocyte proteome reveals differentially altered protein abundances between lean, overweight and morbidly obese human subjects.
abstract: Overweight (OW) and obese individuals are considered to be graded parts of the scale having increasing weight as a common feature. They may not, however, be part of the same continuum and may differ metabolically. In this study we applied an untargeted proteomic approach to compare protein abundances in mature adipocytes derived from the subcutaneous adipose tissue of overweight and morbidly obese female subjects to those of lean age matched controls. Mature adipocytes were isolated from liposuction samples of abdominal subcutaneous adipose tissue collected from both lean (L; n = 7, 23.3 ± 0.4 kg/m(2); mean BMI ± SD), overweight (OW; n = 8, 27.9 ± 0.6 kg/m(2); mean BMI ± SD) and morbidly obese (MOB; n = 7, 44.8 ± 3.8 kg/m(2); mean BMI ± SD) individuals. Total protein extracts were then compared by two-dimensional difference in gel electrophoresis (2D DIGE). One hundred and ten differentially expressed protein spots (i.e., fitting the statistical criteria ANOVA test, p < 0.05; fold-change ≥1.5) were detected, and of these, 89 were identified by MALDI-TOF mass spectrometry. Of these, 66 protein spots were common to both groups whereas 23 were unique to the MOB group. Significant differences were evident in the abundances of key proteins involved in glucose and lipid metabolism, energy regulation, cytoskeletal structure and redox control signaling pathways. Differences in the abundance of some chaperones were also evident. The differentially abundant proteins were investigated using Ingenuity Pathway Analysis (IPA) to establish their associations with known biological functions. The network identified in the OW group with the highest score relates to-: cell-to-cell signaling and interaction; in contrast, in the MOB group the major interacting pathways are associated with lipid metabolism, small molecule biochemistry and cancer. The differences in abundance of the differentially regulated proteins were validated by immunoblotting. These findings provide insights into metabolic differences in OW and MOB individuals.
authors.affiliation: Obesity Research Center, College of Medicine, King Saud University, P.O. Box 2925 (98), Riyadh 11461, Saudi Arabia.
authors.forename: Hicham
authors.initials: H
authors.lastname: Benabdelkamel
authors.affiliation: Obesity Research Center, College of Medicine, King Saud University, P.O. Box 2925 (98), Riyadh 11461, Saudi Arabia.
authors.forename: Afshan
authors.initials: A
authors.lastname: Masood
authors.affiliation: Obesity Research Center, College of Medicine, King Saud University, P.O. Box 2925 (98), Riyadh 11461, Saudi Arabia.
authors.forename: Ghaith M
authors.initials: GM
authors.lastname: Almidani
authors.affiliation: Obesity Research Center, College of Medicine, King Saud University, P.O. Box 2925 (98), Riyadh 11461, Saudi Arabia.
authors.forename: Abdulmajeed A
authors.initials: AA
authors.lastname: Alsadhan
authors.affiliation: Department of Surgery, Security Forces Hospital, P.O. Box 3643, Riyadh 11481, Saudi Arabia.
authors.forename: Abdulelah F
authors.initials: AF
authors.lastname: Bassas
authors.affiliation: Obesity Research Center, College of Medicine, King Saud University, P.O. Box 2925 (98), Riyadh 11461, Saudi Arabia; Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, School of Medicine, MS8106, E. 19th Avenue, Anschutz Medical Campus, University of Colorado Denver, Aurora, CO 80045, USA.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Duncan
authors.affiliation: Obesity Research Center, College of Medicine, King Saud University, P.O. Box 2925 (98), Riyadh 11461, Saudi Arabia; Department of Medicine, College of Medicine, King Saud University, P.O. Box 2925 (38), Riyadh 11461, Saudi Arabia. Electronic address: aalfadda@ksu.edu.sa.
authors.forename: Assim A
authors.initials: AA
authors.lastname: Alfadda
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D015992:Body Mass Index; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D050356:Lipid Metabolism; D009767:Obesity, Morbid / Q000378:metabolism* / Q000473:pathology; D060066:Protein Interaction Maps; D020543:Proteome / Q000302:isolation & purification*; D040901:Proteomics / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D050507:Subcutaneous Fat, Abdominal / Q000166:cytology* / Q000378:metabolism / Q000473:pathology
chemical_list: D020543:Proteome
keywords: Human adipocytes; Lean; Obese; Obesity; Overweight; Proteomics