ACE gene titration in mice uncovers a new mechanism for ACE on the control of body weight

A. S. Heimann, M. H. Favarato, F. C. Gozzo, V. Rioli, F. R. Carreño, M. N. Eberlin, E. S. Ferro, J. H. Krege, J. E. Krieger

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


Mice harboring 1, 2, or 3 copies of the ansiotensin-converting enzyme (ACE) gene were used to evaluate the quantitative role of the ACE locus on obesity. Three-copy mice fed with a high-fat diet had lower body weight and peri-epididymal adipose tissue than did 1- and 2-copy mice (P < 0.05). On regular diet, 3-copy mice had to eat more to maintain the same body weight; on a high-fat diet, they ate the same but weighed less than 1- and 2-copy mice (P < 0.05), indicating a higher metabolic rate in 3-copy mice that was not affected by ANG II AT1 blocker treatment. A catalytically inactive form of thimet oligopeptidase (EC; EP24.15) was used to isolate ACE substrates from adipose tissue. Liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) identified 162 peptide peaks; 16 peptides were present in both groups (1-and 3-copy mice fed with a high-fat diet), whereas 58 of the 72 unique peptides were found only in the 3-copy mice. Peptide size distribution was shifted to lower molecular weight in 3-copy mice. Two of the identified peptides, LVVYPWTQRY and VVYPWTQRY, which are ACE substrates, inhibited in vitro protein kinase C phosphorylation in a concentration-dependent manner. In addition, neurolysin (EC; EP24.16) activity was lower in fat tissue from 3- vs. 1-copy mice (P < 0.05). Taken together, these results provide evidence that ACE is associated with body weight and peri-epididymal fat accumulation. This response may involve the generation of oligopeptides that inhibit the activity of EP24.16 and other oligopeptidases within the adipose tissue.

Original languageEnglish (US)
Pages (from-to)173-182
Number of pages10
JournalPhysiological Genomics
StatePublished - Apr 2005
Externally publishedYes


  • Angiotensin converting enzyme
  • EP24.16
  • Insulin resistance
  • Oligopeptides
  • Peptides

ASJC Scopus subject areas

  • Genetics
  • Physiology


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