The ménage à trois of autophagy, lipid droplets and liver disease

Abstract

Autophagic pathways cross with lipid homeostasis and thus provide energy and essential building blocks that are indispensable for liver functions. Energy deficiencies are compensated by breaking down lipid droplets (LDs), intracellular organelles that store neutral lipids, in part by a selective type of autophagy, referred to as lipophagy. The process of lipophagy does not appear to be properly regulated in fatty liver diseases (FLDs), an important risk factor for the development of hepatocellular carcinomas (HCC). Here we provide an overview on our current knowledge of the biogenesis and functions of LDs, and the mechanisms underlying their lysosomal turnover by autophagic processes. This review also focuses on nonalcoholic steatohepatitis (NASH), a specific type of FLD characterized by steatosis, chronic inflammation and cell death. Particular attention is paid to the role of macroautophagy and macrolipophagy in relation to the parenchymal and non-parenchymal cells of the liver in NASH, as this disease has been associated with inappropriate lipophagy in various cell types of the liver.

Angelica Polysaccharide Antagonizes 5-FU-Induced Oxidative Stress Injury to Reduce Apoptosis in the Liver Through Nrf2 Pathway

“…Ppargc1a promotes mitochondrial biogenesis, oxidation capacity and fatty acid b oxidation by increasing the expression and activation of various transcription factors (such as PPAR-alpha) (47). In terms of fatty acid decomposition, the key TG hydrolase in the liver is Pnpla2, and Sirt1 can regulate fat mobilization through Foxo1mediated Pnpla2 expression (48)(49)(50). Therefore, we focused on verifying the expression of five lipid-metabolism-related genes in vitro, and the results obtained were consistent with those of the in vivo experiments.…”

An Autophagy Modulator Peptide Prevents Lung Function Decrease and Corrects Established Inflammation in Murine Models of Airway Allergy

“…Hence, autophagy participates in the immunopathology of inflammatory diseases. Some alterations—either upregulation or downregulation—in several autophagy pathways, have thus been implicated in numerous (auto)immune and inflammatory disorders, such as systemic lupus erythematosus, Sjögren’s syndrome (SS), rheumatoid arthritis, psoriasis, some neuroinflammatory and neurodegenerative diseases including multiple sclerosis, chronic inflammatory demyelinating polyneuropathies, amyotrophic lateral sclerosis, and Huntington’s, Alzheimer’s, and Parkinson’s diseases [ 9 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ] and also in metabolic diseases, cancer, infection and ageing. In asthma, results are still scarce and interrelationships between asthma and autophagy remain poorly established [ 26 , 27 , 28 ].…”

Therapeutic Targeting of Nonalcoholic Fatty Liver Disease by Downregulating SREBP-1C Expression via AMPK-KLF10 Axis

“…NAFLD encompasses a spectrum of diseases including simple steatosis or nonalcoholic fatty liver (NAFL), the nonalcoholic steatohepatitis (NASH) which is a more progressive and severe stage of NAFLD and is often accompanied by fibrosis that can progress to cirrhosis or hepatocellular carcinoma (HCC) ( Huang et al, 2021 ). The development of NAFLD and the following NASH is a complex process that accumulation of lipid droplets within hepatocytes occurs as a result of a dysregulated lipid metabolism, which is closely associated with a metabolic syndrome including obesity, insulin resistance, dyslipidemia and hypertension ( Filali-Mouncef et al, 2021 ). So far, the molecular basis of this disease entity is still unclear and the effective preventive or therapeutic agents for NAFLD is still lacking.…”