Antioxidant Effects of Oral Ang-(1-7) Restore Insulin Pathway and RAS Components Ameliorating Cardiometabolic Disturbances in Rats

Autor: Aline Cruz Zacarias, Renata Guerra de Sá, Andréia Carvalho Alzamora, Vivian Paulino Figueiredo, Robson A.S. Santos, Frank Silva Bezerra, Wanderson Geraldo de Lima, Maria Andrea Barbosa, Uberdan Guilherme Mendes de Castro
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Aging
Administration
Oral
medicine.disease_cause
Biochemistry
Antioxidants
Renin-Angiotensin System
0302 clinical medicine
Insulin receptor substrate
Insulin
Metabolic Syndrome
biology
lcsh:Cytology
General Medicine
Catalase
Liver
Angiotensin-Converting Enzyme 2
Research Article
Signal Transduction
Bioquímica
Síndrome Metabólica
medicine.medical_specialty
Article Subject
Peptidyl-Dipeptidase A
Diet
High-Fat
Receptor
Angiotensin
Type 1
03 medical and health sciences
Dieta Hiperlipidica
Internal medicine
TBARS
medicine
Animals
lcsh:QH573-671
Muscle
Skeletal
Cyclodextrins
Sistema Renina Angiotensina
business.industry
Superoxide Dismutase
Lipid metabolism
Cell Biology
medicine.disease
Peptide Fragments
Rats
Insulin receptor
Oxidative Stress
030104 developmental biology
Endocrinology
Gene Expression Regulation
biology.protein
Liver function
Metabolic syndrome
Angiotensin I
business
030217 neurology & neurosurgery
GLUT4
Oxidative stress
Zdroj: Oxidative Medicine and Cellular Longevity
Repositório Institucional da UFMG
Universidade Federal de Minas Gerais (UFMG)
instacron:UFMG
Repositório Institucional da UFOP
Universidade Federal de Ouro Preto (UFOP)
instacron:UFOP
Oxidative Medicine and Cellular Longevity, Vol 2019 (2019)
ISSN: 1942-0994
1942-0900
Popis: In prevention studies of metabolic syndrome (MetS), Ang-(1-7) has shown to improve the insulin signaling. We evaluated the HPβCD/Ang-(1-7) treatment on lipid metabolism, renin-angiotensin system (RAS) components, oxidative stress, and insulin pathway in the liver and gastrocnemius muscle and hepatic steatosis in rats with established MetS. After 7 weeks of high-fat (FAT) or control (CT) diets, rats were treated with cyclodextrin (HPβCD) or HPβCD/Ang-(1-7) in the last 6 weeks. FATHPβCD/empty rats showed increased adiposity index and body mass, gene expression of ACE/ANG II/AT1R axis, and oxidative stress. These results were accompanied by imbalances in the insulin pathway, worsening of liver function, hyperglycemia, and dyslipidemia. Oral HPβCD/Ang-(1-7) treatment decreased ACE and AT1R, increased ACE2 gene expression in the liver, and restored thiobarbituric acid reactive substances (TBARS), catalase (CAT), superoxide dismutase (SOD), insulin receptor substrate (Irs-1), glucose transporter type 4 (GLUT4), and serine/threonine kinase 2 (AKT-2) gene expression in the liver and gastrocnemius muscle improving hepatic function, cholesterol levels, and hyperglycemia in MetS rats. Overall, HPβCD/Ang-(1-7) treatment restored the RAS components, oxidative stress, and insulin signaling in the liver and gastrocnemius muscle contributing to the establishment of blood glucose and lipid homeostasis in MetS rats. Em estudos de prevenção da síndrome metabólica (MetS), a Ang-(1-7) demonstrou melhorar a sinalização da insulina. Nós avaliamos o Tratamento HPβCD/Ang-(1-7) no metabolismo lipídico, componentes do sistema renina-angiotensina (RAS), estresse oxidativo e insulina no fígado e músculo gastrocnêmio e esteatose hepática em ratos com SM estabelecida. Após 7 semanas de alto teor de gordura (FAT) ou controle (CT), os ratos foram tratados com ciclodextrina (HPβCD) ou HPβCD/Ang-(1-7) nas últimas 6 semanas. FATHPβCD/ratos vazios apresentaram aumento do índice de adiposidade e massa corporal, expressão gênica do eixo ACE/ANG II/AT1R e estresse oxidativo. Esses resultados foram acompanhados por desequilíbrios na via da insulina, piora da função hepática, hiperglicemia e dislipidemia. O tratamento oral com HPβCD/Ang-(1-7) diminuiu ACE e AT1R, aumentou a expressão do gene ACE2 no fígado e substâncias reativas ao ácido tiobarbitúrico (TBARS), catalase (CAT), superóxido dismutase (SOD), insulina substrato do receptor (Irs-1), transportador de glicose tipo 4 (GLUT4) e expressão gênica de serina/treonina quinase 2 (AKT-2) no fígado e músculo gastrocnêmio melhorando a função hepática, níveis de colesterol e hiperglicemia em ratos MetS. No geral, O tratamento com HPβCD/Ang-(1-7) restaurou os componentes RAS, estresse oxidativo e sinalização de insulina no fígado e músculo gastrocnêmio contribuindo para o estabelecimento da glicemia e homeostase lipídica em ratos MetS.
Databáze: OpenAIRE
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