Steatosis in metabolic diseases: A focus on lipolysis and lipophagy

Fatty acids (FAs), as part of lipids, are involved in cell membrane composition, cellular energy storage, and cell signaling. FAs can also be toxic when their concentrations inside and/or outside the cell exceed physiological levels, which is called lipotoxicity, and steatosis is a form of lipotoxity. To facilitate the storage of large quantities of FAs in cells, they undergo a process called lipolysis or lipophagy. This review focuses on the effects of lipolytic enzymes including cytoplasmic neutral lipolysis, lysosomal acid lipolysis, and lipophagy. Moreover, the impact of related lipolytic enzymes on lipid metabolism homeostasis and energy conservation, as well as their role in lipid-related metabolic diseases. In addition, we describe how they affect lipid metabolism homeostasis and energy conservation in lipid-related metabolic diseases with a focus on hepatic steatosis and cancer and the pathogenesis and therapeutic targets of AMPK/SIRTs/FOXOs, PI3K/Akt, PPARs/PGC-1 alpha, MAPK/ ERK1/2, TLR4/NF-cB, AMPK/mTOR/TFEB, Wnt/beta-catenin through immune inflammation, oxidative stress and autophagy-related pathways. As well as the current application of lipolytic enzyme inhibitors (especially Monoacylglycerol lipase (MGL) inhibitors) to provide new strategies for future exploration of metabolic programming in metabolic diseases.

Automated summary

This review focuses on the effects of lipolytic enzymes on lipid metabolism homeostasis and energy conservation, as well as their role in lipid-related metabolic diseases. It also explores the impact of these enzymes on hepatic steatosis and cancer through immune inflammation, oxidative stress, and autophagy-related pathways. Additionally, it examines the current application of lipolytic enzyme inhibitors, especially Monoacylglycerol lipase (MGL) inhibitors, as potential strategies for future exploration of metabolic programming in metabolic diseases.