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

Autor(es)

Heimann‚ AS ; Favarato‚ MH ; Gozzo‚ FC ; Rioli‚ V. ; Carreno‚ FR ; Eberlin‚ MN ; Ferro‚ ES ; Krege‚ JH ; Krieger‚ JE

• Tipo de documento: Artigo Científico
• Fonte: Physiological Genomics; v. 20, n. 2, p. 173-182, 2005.

Resumo

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)

• Processo FAPESP: 00/11176-2 - Técnicas modernas em espectrometria de massas e suas aplicações em química e bioquímica
• Beneficiário: Marcos Nogueira Eberlin
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 99/01983-9 - Bases moleculares e celulares da biologia da peptidases: projeto ii do laboratorio de comunicacao celular.
• Beneficiário: Emer Suavinho Ferro
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 01/00009-0 - Estudo integrado da hipertensão arterial: caracterização molecular e funcional do sistema cardiovascular
• Beneficiário: Eduardo Moacyr Krieger
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 01/11478-1 - O papel da enzima conversora de angiotensina I no controle do peso durante a mudança de hábito alimentar
• Beneficiário: Andrea Sterman Heimann
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 01/07544-9 - Projeto genoma estrutural.
• Beneficiário: Emer Suavinho Ferro
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 03/01062-8 - Mecanismos de acao do gene da enzima conversora de angiotensina i na modulacao do peso corporal-alteracoes no consumo alimentar e na regulacao metabolica.
• Beneficiário: Maria Helena Sampaio Favarato
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica