Metabolic Role of Autophagy in the Pathogenesis and Development of NAFLD

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver disease, ranging from simple steatosis to hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Liver fibrosis, which portends a poor prognosis in NAFLD, is characterized by the excessive accumulation of extracellular matrix (ECM) proteins resulting from abnormal wound repair response and metabolic disorders. Various metabolic factors play crucial roles in the progression of NAFLD, including abnormal lipid, bile acid, and endotoxin metabolism, leading to chronic inflammation and hepatic stellate cell (HSC) activation. Autophagy is a conserved process within cells that removes unnecessary or dysfunctional components through a lysosome-dependent regulated mechanism. Accumulating evidence has shown the importance of autophagy in NAFLD and its close relation to NAFLD progression. Thus, regulation of autophagy appears to be beneficial in treating NAFLD and could become an important therapeutic target.

Bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate Enhances foxo1-Mediated Lipophagy to Remodel Lipid Metabolism in Zebrafish Liver

“…As the primary enzyme involved in cellular response to oxidative damage, SOD may be more sensitive to toxic substances than CAT and GSH. , Thus, due to the compensation mechanism of organisms, the initial perturbations of TBPH on CAT and GSH can be compensated at 0.1 μg/L, while those on SOD are not sufficient to be offset . These results confirmed that embryonic exposure to TBPH led to hepatic lipid metabolism disorders and oxidative stress, the most prominent features of NAFLD . Consistently, a previous study found that TBPH aggregated hepatic lipid metabolic disorders induced by diet and caused oxidative stress, leading to the promotion of NAFLD progression .…”

“…62 These results confirmed that embryonic exposure to TBPH led to hepatic lipid metabolism disorders and oxidative stress, the most prominent features of NAFLD. 63 Consistently, a previous study found that TBPH aggregated hepatic lipid metabolic disorders induced by diet and caused oxidative stress, leading to the promotion of NAFLD progression. 16 In addition, the administration of DEHP, a homologue of TBPH, was shown to disrupt lipid metabolic homeostasis in mouse livers and induce hepatic inflammation, as seen in NAFLD.…”

Probing Deposit-Driven Age-Related Macular Degeneration Via Thicknesses of Outer Retinal Bands and Choroid: ALSTAR2 Baseline

“…Details of the study protocol and baseline demographic characteristics have been described. 29 , 30 To ensure good fixation, one eye from each recruited patient, that is, the eye with better acuity, was chosen for the study. All subjects underwent complete eye examination, multimodal imaging (i.e.…”

Bacteroides and NAFLD: pathophysiology and therapy

“…Lipopolysaccharide (LPS), a typical pathogen-associated molecular pattern, mediates inflammatory injury in hepatocytes and has been found to induce inflammatory liver injury through the downstream toll-like receptor 4 (TLR4) signaling pathway (Qi et al, 2020;An et al, 2022). LPS is a crucial factor in the induction of inflammatory responses in the liver and is expressed abundantly in patients with NASH (Carpino et al, 2020).…”