title: Oral Angiotensin-(1-7) prevented obesity and hepatic inflammation by inhibition of resistin/TLR4/MAPK/NF-κB in rats fed with high-fat diet.
abstract: Obesity is characterized by a pro-inflammatory state commonly associated with type 2 diabetes and fat-liver disease. In the last few years, different studies pointed out the role of Angiotensin (Ang)-(1-7) in the metabolic regulation. The aim of the present study was to evaluate the effect of oral-administration of Ang-(1-7) in metabolism and inflammatory state of high-fat feed rats. Twenty-four male Sprague Dawley rats were randomized into three groups: High Fat Diet (HFD); Standard Diet (ST); High Fat Diet+Angiotensin-(1-7) [HFD+Ang-(1-7)]. Glycemic profile was evaluated by glucose tolerance and insulin sensitivity tests, plasmatic glucose and insulin. Cholesterol, HDL and triglycerides analyses presented lipidic profile. RT-PCR evaluated mRNA expression to ACE, ACE2, resistin, TLR4, IL-6, TNF-α and NF-κB genes. The main results showed that oral Ang-(1-7) decreased body weight and abdominal fat-mass. In addition, HFD+Ang-(1-7) treated rats presented enhanced glucose tolerance, insulin-sensitivity and decreased plasma-insulin levels, as well as a significant decrease in circulating lipid levels. These alterations were accompanied by a marked decreased expression of resistin, TLR4, ACE and increased ACE2 expression in liver. Furthermore, Ang-(1-7) decreases phosphorylation of MAPK and increases NF-κB expression. These alterations diminished expression of interleukin-6 and TNF-α, ameliorate inflammatory state in liver. In summary, the present study showed that oral-treatment with Ang-(1-7) in high-fat feed rats improved metabolism down-regulating resistin/TLR4/NF-κB-pathway.
authors.affiliation: Laboratory of Health Science, Postgraduate Program in Health Sciences, Universidade Estadual de Montes Claros-UNIMONTES, Montes Claros, MG, Brazil. sergiosousas@hotmail.com
authors.forename: Sérgio Henrique Sousa
authors.initials: SH
authors.lastname: Santos
authors.forename: João Marcus Oliveira
authors.initials: JM
authors.lastname: Andrade
authors.forename: Luciana Rodrigues
authors.initials: LR
authors.lastname: Fernandes
authors.forename: Ruben D M
authors.initials: RD
authors.lastname: Sinisterra
authors.forename: Frederico B
authors.initials: FB
authors.lastname: Sousa
authors.forename: John David
authors.initials: JD
authors.lastname: Feltenberger
authors.forename: Jaqueline Izaura
authors.initials: JI
authors.lastname: Alvarez-Leite
authors.forename: Robson Augusto Souza
authors.initials: RA
authors.lastname: Santos
mesh_terms: D000803:Angiotensin I / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D059305:Diet, High-Fat; D005951:Glucose Tolerance Test; D007249:Inflammation / Q000188:drug therapy / Q000517:prevention & control*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008075:Lipoproteins, HDL / Q000097:blood; D008099:Liver / Q000187:drug effects*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009765:Obesity / Q000188:drug therapy / Q000517:prevention & control*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D052243:Resistin / Q000037:antagonists & inhibitors; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D007328:Insulin; D008075:Lipoproteins, HDL; D016328:NF-kappa B; D010446:Peptide Fragments; D052243:Resistin; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D014280:Triglycerides; D000803:Angiotensin I; D002784:Cholesterol; D020928:Mitogen-Activated Protein Kinases; C118790:angiotensin I (1-7)