Programmed cell death and lipid metabolism of macrophages in NAFLD

Abstract

Non-alcoholic fatty liver disease (NAFLD) has now become the leading chronic liver disease worldwide with lifestyle changes. This may lead to NAFLD becoming the leading cause of end-stage liver disease in the future. To date, there are still no effective therapeutic drugs for NAFLD. An in-depth exploration of the pathogenesis of NAFLD can help to provide a basis for new therapeutic agents or strategies. As the most important immune cells of the liver, macrophages play an important role in the occurrence and development of liver inflammation and are expected to become effective targets for NAFLD treatment. Programmed cell death (PCD) of macrophages plays a regulatory role in phenotypic transformation, and there is also a certain connection between different types of PCD. However, how PCD regulates macrophage polarization has still not been systematically elucidated. Based on the role of lipid metabolic reprogramming in macrophage polarization, PCD may alter the phenotype by regulating lipid metabolism. We reviewed the effects of macrophages on inflammation in NAFLD and changes in their lipid metabolism, as well as the relationship between different types of PCD and lipid metabolism in macrophages. Furthermore, interactions between different types of PCD and potential therapeutic agents targeting of macrophages PCD are also explored.

Non-alcoholic fatty liver disease: Immunological mechanisms and current treatments

“…Liver resident KCs are a large population of macrophages as well as other subsets of macrophages such as monocyte-derived macrophages and liver capsular macrophages[ 45 ]. M1 macrophages have a pro-inflammatory phenotype and are induced by mediators such as LPS and interferon-γ (IFN-γ) and their activation causes secretion of pro-inflammatory cytokines such as IL-1β, IL-6 and TNF-α[ 46 , 47 ]. On the other hand, M2 macrophages have an anti-inflammatory phenotype and are induced by Th2 cytokines such as IL-4 and IL-13, causing secretion of anti-inflammatory factors such as IL-10 and transforming growth factor-β (TGF-β)[ 46 , 47 ].…”

“…M1 macrophages have a pro-inflammatory phenotype and are induced by mediators such as LPS and interferon-γ (IFN-γ) and their activation causes secretion of pro-inflammatory cytokines such as IL-1β, IL-6 and TNF-α[ 46 , 47 ]. On the other hand, M2 macrophages have an anti-inflammatory phenotype and are induced by Th2 cytokines such as IL-4 and IL-13, causing secretion of anti-inflammatory factors such as IL-10 and transforming growth factor-β (TGF-β)[ 46 , 47 ]. M2-type macrophages have also been reported to induce M1-type KCs apoptosis decreasing disease progression[ 48 ].…”

Foxa2 attenuates steatosis and inhibits the NF-κB/IKK signaling pathway in nonalcoholic fatty liver disease

“…Disorders of lipid metabolism contribute to the progression of NAFLD ( Xiao et al, 2023 ). Accelerated lipid consumption and/or inhibited lipid synthesis are considered effective strategies for reducing hepatic lipid accumulation ( Fang et al, 2019 ).…”

Multicolor Two-Photon Microscopy Imaging of Lipid Droplets and Liver Capsule Macrophages In Vivo

“…8−10 Dysregulated lipid metabolism in NAFLD may promote the progression of inflammation by affecting the function of macrophages. 11 Understanding liver disease requires the elucidation of the distribution and role of immune cells in NAFLD. Therefore, a specific tool is required to directly observe interactions between LDs, which is a representative hallmark of NAFLD, and hepatic macrophages.…”

“…Macrophages are abundant in the liver because they also serve as an immune organ. Excessive accumulation of lipids in the liver causes lipotoxicity, leading to liver damage, which promotes the expansion of hepatic macrophages. , Macrophages in the liver cause inflammation and differentiate into pro-inflammatory macrophages, further promoting the progression of NAFLD. − Dysregulated lipid metabolism in NAFLD may promote the progression of inflammation by affecting the function of macrophages . Understanding liver disease requires the elucidation of the distribution and role of immune cells in NAFLD.…”