An Asp7Gly substitution in PPARG is associated with decreased transcriptional activation activity

PLoS One. 2014 Jan 23;9(1):e86954. doi: 10.1371/journal.pone.0086954. eCollection 2014.

Abstract

As the master regulator of adipogenesis, peroxisome proliferator-activated receptor gamma (PPARG) is required for the accumulation of adipose tissue and hence contributes to obesity. A previous study showed that the substitution of +20A>G in PPARG changed the 7(th) amino acid from Asp to Gly, creating a mutant referred to as PPARG Asp7Gly. In this study, association analysis indicated that PPARG Asp7Gly was associated with lower body height, body weight and heart girth in cattle (P<0.05). Overexpression of PPARG in NIH3T3-L1 cells showed that the Asp7Gly substitution may cause a decrease in its adipogenic ability and the mRNA levels of CIDEC (cell death-inducing DFFA-like effector c) and aP2, which are all transcriptionally activated by PPARG during adipocyte differentiation. A dual-luciferase reporter assay was used to analyze the promoter activity of CIDEC. The results confirmed that the mutant PPARG exhibited weaker transcriptional activation activity than the wild type (P<0.05). These findings likely explain the associations between the Asp7Gly substitution and the body measurements. Additionally, the Asp7Gly mutation may be used in molecular marker assisted selection (MAS) of cattle breeding in the future.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / cytology*
  • Adipocytes / metabolism
  • Adipogenesis / physiology*
  • Adipose Tissue
  • Animals
  • Body Height
  • Body Weight
  • Cattle
  • Cell Differentiation*
  • Humans
  • Luciferases
  • Mice
  • Mutation / genetics*
  • NIH 3T3 Cells
  • PPAR gamma / genetics*
  • Promoter Regions, Genetic / genetics*
  • Proteins / genetics
  • Transcription, Genetic*

Substances

  • PPAR gamma
  • Proteins
  • fat-specific protein 27, mouse
  • Luciferases

Grants and funding

This study was supported by the National Natural Science Foundation of China (Grant No. 31272408), URL: http://www.nsfc.gov.cn/; National 863 Program of China (Grant No. 2013AA102505), URL: http://www.863.gov.cn/; Program of National Beef Cattle and Yak Industrial Technology System (Grant No. CARS-38), URL: http://www.beefsys.com/; College Industrialization Project of Jiangsu Province (JHB2012-32), URL: http://www.ec.js.edu.cn/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.