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

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.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.The search found 5754 articles, with 48 matching the eligibility criteria, comprising of 1033 animals. 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.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.