Effects of high-fat diet-induced diabetes on autophagy in the murine liver: A systematic review and meta-analysis

Autor(es)

da Cruz, Larissa Lopes ; Vesentini, Giovana ; Sinzato, Yuri Karen ; Villaverde, Ana Izabel Silva Balbin ; Volpato, Gustavo Tadeu ; Damasceno, Debora Cristina

• Tipo de documento: Artigo Científico
• Fonte: Life Sciences; v. 309, p. 13-pg., 2022-10-02.

Resumo

Aims: We conducted a meta-analysis to investigate whether diabetes induced by a high-fat diet (HFD) has the potential to alter the process of autophagy in the murine liver.Methods: A systematic literature search was performed with electronic databases (PubMed, EMBASE, Web of Science). Study design, population, intervention, outcome, and risk of bias were analyzed. Given the availability of studies, a quantitative meta-analysis including 23 studies was performed.Key findings: The search found 5754 articles, with 48 matching the eligibility criteria, comprising of 1033 ani-mals. The meta-analysis showed that diabetic murines fed with HFD presented an absence of p62 degradation (SMD 4.63, 95 % CI 2.02 to 7.24, p = 0.0005; I2 = 77 %), higher expression of p-mTOR/mTOR (SMD 5.20, 95 % CI 1.00 to 9.39, p = 0.01; I2 = 78 %), and a decreased p-AMPK/AMPK ratio (SMD-2.02, 95 % CI-3.96 to-0.09, p = 0.04; I2 = 85 %) when compared to nondiabetic murines. When associated with streptozotocin, the animals presented decreased ATG-7 and LC3-II. The meta-regression results showed a decrease in autophagy responses due to increased glycemic levels, fat content, and long-term exposure to HFD, and advanced animal age. The common and species-specific protein responses were also consistent with the inhibition of autophagy. Significance: The normal process of autophagy mechanisms in the liver is less competent after HFD consumption. The destabilization of (auto)phagolysosomes contributes to the perpetuation of diabetes, metabolic dysfunction -associated fatty liver disease, and cell death. (AU)

• Processo FAPESP: 16/25207-5 - Avaliação de descendentes expostas ao diabete moderado intrautero, submetidas à dieta hiperlipídica no período pós-natal e tratadas com mistura de cálcio e vitamina D durante a prenhez
• Beneficiário: Débora Cristina Damasceno
• Modalidade de apoio: Auxílio à Pesquisa - Regular