Advanced search
Start date
Betweenand
Related content
(Reference retrieved automatically from Google Scholar through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

Full text
Author(s):
Heimann‚ AS ; Favarato‚ MH ; Gozzo‚ FC ; Rioli‚ V. ; Carreno‚ FR ; Eberlin‚ MN ; Ferro‚ ES ; Krege‚ JH ; Krieger‚ JE
Total Authors: 9
Document type: Journal article
Source: Physiological Genomics; v. 20, n. 2, p. 173-182, 2005.
Abstract

Mice harboring 1, 2, or 3 copies of the angiotensin-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 AT(1) blocker treatment. A catalytically inactive form of thimet oligopeptidase (EC 3.4.24.15; 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 3.4.24.16; 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. (AU)

FAPESP's process: 00/11176-2 - Modern techniques in mass spectrometry and their applications in chemistry and biochemistry
Grantee:Marcos Nogueira Eberlin
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 01/00009-0 - An integrated approach for the dissection of primary hypertension: molecular and functional characterization of the cardiovascular system
Grantee:Eduardo Moacyr Krieger
Support Opportunities: Research Projects - Thematic Grants