Obesity, inflammation and resting energy expenditure: possible mechanism of progranulin in this pathway

Minerva Endocrinol. 2012 Sep;37(3):255-66.

Abstract

Aim: 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).

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Algorithms
  • Basal Metabolism*
  • Biomarkers / blood
  • Body Composition
  • Body Mass Index
  • Cross-Sectional Studies
  • Electric Impedance
  • Female
  • Gene Expression Regulation
  • Humans
  • Inflammation / blood
  • Inflammation / metabolism*
  • Intercellular Signaling Peptides and Proteins / blood*
  • Intercellular Signaling Peptides and Proteins / genetics
  • Male
  • Middle Aged
  • Mitogen-Activated Protein Kinase Kinases / blood
  • Obesity / blood
  • Obesity / metabolism*
  • Overweight / metabolism
  • Progranulins
  • Proto-Oncogene Proteins c-akt / blood
  • RNA, Messenger / blood
  • Sampling Studies

Substances

  • Biomarkers
  • GRN protein, human
  • Intercellular Signaling Peptides and Proteins
  • Progranulins
  • RNA, Messenger
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinase Kinases