title: Obesity, inflammation and resting energy expenditure: possible mechanism of progranulin in this pathway.
abstract: OBJECTIVE
  The aim of the study was to measure circulating PGRN levels and to investigate its potential correlation with resting metabolic rate and obesity related complications. Moreover, to investigate on the PGRN and some important gene expressions in energy expenditure in vitro in samples of PBMCs derived from all participants of our study in a cellular model.
  
  
  METHODS
  Of the 163 participants who were recruited for the current cross-sectional study, 37 (22.69%) were normal weight (18.5≤BMI<25), 53 (32.51%) were overweight (25≤BMI<30), 48 (29.44%) were categorized as class I obese (BMI 30 -34.9) and 25 (15.33%) were classified as class II and III obese (BMI≥35). All participants were assessed for the measurement of RMR by means of indirect calorimetry following an overnight fasting. Body composition was analyzed with the Bioelectrical Impedance technique by the BODY COMPOSITION ANALYZER BC-418M -Tanita. The PBMCs were separated from whole blood by Ficoll-hypaque technique. Total cellular RNA was extracted and the cDNA was synthesized. This process was followed by real-time PCR using specific primer pairs for PGRN, AKT, MAPK and mRNA, and beta actin mRNA was used as the internal control. Circulating PGRN was measured with the use of ELISA method.
  
  
  RESULTS
  The circulating levels and gene expressions of PGRN rose in parallel with the increase of body weight. However, there was significant difference in the strength of association between circulating PGRN as well as PGRN gene expression and obesity-related variables. Moreover, PGRN gene expression had significant correlation with BMI, visceral fat, MAPK and AKT gene expression. The increased mass of visceral fat in correlation with the increased PGRN levels was more pronounced in high or normal resting metabolic rate group compared with the group with low resting metabolic rate. After adjusting for BMI and gender, we found that circulating PGRN can predict the RMR/kg independent of other variables such as TG, HDL, and hs-CRP (P=0.03).
  
  
  CONCLUSIONS
  PGRN associated with obesity and glucose homeostasis and may predict the resting metabolic rate levels independent of confounder factors. Experimental study may clarify the PGRN role in obesity etiology through metabolism regulation.
authors: Endocrinology and Metabolism Research Institute, Tehran University of Medical SciencesTehran, Iran. ahosseinnezhad@sina.tums.ac.ir
authors: A
authors: A
authors: Hossein-Nezhad
authors: K
authors: K
authors: Mirzaei
authors: H
authors: H
authors: Ansar
authors: S
authors: S
authors: Emam-Gholipour
authors: A
authors: A
authors: Tootee
authors: S A
authors: SA
authors: Keshavarz
mesh_terms: D000328:Adult; D000465:Algorithms; D001481:Basal Metabolism; D015415:Biomarkers / Q000097:blood; D001823:Body Composition; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D017097:Electric Impedance; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020929:Mitogen-Activated Protein Kinase Kinases / Q000097:blood; D009765:Obesity / Q000097:blood / Q000378:metabolism*; D050177:Overweight / Q000378:metabolism; D000077153:Progranulins; D051057:Proto-Oncogene Proteins c-akt / Q000097:blood; D012333:RNA, Messenger / Q000097:blood; D012494:Sampling Studies
chemical_list: D015415:Biomarkers; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins; D012333:RNA, Messenger; D051057:Proto-Oncogene Proteins c-akt; D020929:Mitogen-Activated Protein Kinase Kinases