Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/54090
Type: Artigo de periódico
Title: ACE gene titration in mice uncovers a new mechanism for ACE on the control of body weight
Author: Heimann, AS
Favarato, MH
Gozzo, FC
Rioli, V
Carreno, FR
Eberlin, MN
Ferro, ES
Krege, JH
Krieger, JE
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.
Subject: insulin resistance
peptides
oligopeptides
EP24.16
angiotensin converting enzyme
Country: EUA
Editor: Amer Physiological Soc
Rights: fechado
Identifier DOI: 10.1152/physiolgenomics.00145.2004
Date Issue: 2005
Appears in Collections:Unicamp - Artigos e Outros Documentos

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