Targeting lipophagy as a potential therapeutic strategy for nonalcoholic fatty liver disease

Li, Hongying; Peng, Zong–Gen

doi:10.1016/j.bcp.2022.114933

Cited by 25 publications

(13 citation statements)

References 158 publications

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“…As such, the intracellularly accumulated TGs may lead to the occurrence of liver steatosis due to the fact that long-term over-accumulated TGs are one of the pathogenetic markers of early chronic liver diseases [ 46 , 47 ]. Furthermore, long-term redundant LDs commonly accompany liver injury and inflammation [ 47 , 48 ] and hence facilitate the progression of NAFLD [ 49 , 50 ]. We found that the high expression of HSD17B13 induced LD accumulation and directly caused liver injury as well as an increase in intracellular ALT and AST accompanied by the higher expression of inflammatory factors ( Figure 3 E–G).…”

Section: Discussionmentioning

confidence: 99%

Down-Regulating the High Level of 17-Beta-Hydroxysteroid Dehydrogenase 13 Plays a Therapeutic Role for Non-Alcoholic Fatty Liver Disease

Wang

et al. 2022

IJMS

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Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, and there is no specific drug to treat it. Recent results showed that 17-beta-hydroxysteroid dehydrogenase type 13 (HSD17B13) is associated with liver diseases, but these conclusions are controversial. Here, we showed that HSD17B13 was more highly expressed in the livers of NAFLD patients, and high expression was induced in the livers of murine NAFLD models and cultural hepatocytes treated using various etiologies. The high HSD17B13 expression in the hepatocytes facilitated the progression of NAFLD by directly stabilizing the intracellular lipid drops and by indirectly activating hepatic stellate cells. When HSD17B13 was overexpressed in the liver, it aggravated liver steatosis and fibrosis in mice fed with a high-fat diet, while down-regulated the high expression of HSD17B13 by short hairpin RNAs produced a therapeutic effect in the NAFLD mice. We concluded that high HSD17B13 expression is a good target for the development of drugs to treat NAFLD.

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Section: Discussionmentioning

confidence: 99%

Down-Regulating the High Level of 17-Beta-Hydroxysteroid Dehydrogenase 13 Plays a Therapeutic Role for Non-Alcoholic Fatty Liver Disease

Wang

et al. 2022

IJMS

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“…During starvation, specifically glucose or amino acid deprivation, autophagy pathway in liver is upregulated by interfering mTOR activation via activation of cAMP-AMPK-TSC1/2 inhibitory pathway [ 101 , 102 ]. In diet-induced NASH, autophagy, especially lipophagy, occurs [ 103 , 104 , 105 , 106 ]. Increased lipophagy in NASH may reflect decreased mTOR activity due to P-JNK inhibition of insulin receptor signaling in NASH.…”

Section: Hepatic Mapk Mediates Progression Of Nafl/nashmentioning

confidence: 99%

Mechanism and Therapeutic Targets of c-Jun-N-Terminal Kinases Activation in Nonalcoholic Fatty Liver Disease

et al. 2022

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Non-alcoholic fatty liver (NAFL) is the most common chronic liver disease. Activation of mitogen-activated kinases (MAPK) cascade, which leads to c-Jun N-terminal kinase (JNK) activation occurs in the liver in response to the nutritional and metabolic stress. The aberrant activation of MAPKs, especially c-Jun-N-terminal kinases (JNKs), leads to unwanted genetic and epi-genetic modifications in addition to the metabolic stress adaptation in hepatocytes. A mechanism of sustained P-JNK activation was identified in acute and chronic liver diseases, suggesting an important role of aberrant JNK activation in NASH. Therefore, modulation of JNK activation, rather than targeting JNK protein levels, is a plausible therapeutic application for the treatment of chronic liver disease.

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“…However, the original assumption that steatosis always precedes inflammation is not always correct; in fact, NASH can also be the initial hepatic injury: it is the timing and the combination of insults that determine whether steatosis or NASH will occur first [ 33 ]. Recently, a deficit of lipophagy has been identified as a further contributor to lipid overaccumulation in NAFLD pathogenesis [ 34 ]. Lipophagy is a highly regulated step process that consists of: (1) protein-mediated sequestration of lipid droplets within cytosolic vesicles and formation of a phagosome; (2) transport of a phagosome to a lysosome and formation of the autophagolysosome; and (3) lipid degradation by lysosomal lipases [ 35 ].…”

Section: Non-alcoholic Fatty Liver Disease and Non-alcoholic Steatohe...mentioning

confidence: 99%

Age-Related NAFLD: The Use of Probiotics as a Supportive Therapeutic Intervention

Campagnoli

Marchesi

Vairetti

et al. 2022

Cells

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Human aging, a natural process characterized by structural and physiological changes, leads to alterations of homeostatic mechanisms, decline of biological functions, and subsequently, the organism becomes vulnerable to external stress or damage. In fact, the elderly population is prone to develop diseases due to deterioration of physiological and biological systems. With aging, the production of reactive oxygen species (ROS) increases, and this causes lipid, protein, and DNA damage, leading to cellular dysfunction and altered cellular processes. Indeed, oxidative stress plays a key role in the pathogenesis of several chronic disorders, including hepatic diseases, such as non-alcoholic fatty liver disease (NAFLD). NAFLD, the most common liver disorder in the Western world, is characterized by intrahepatic lipid accumulation; is highly prevalent in the aging population; and is closely associated with obesity, insulin resistance, hypertension, and dyslipidemia. Among the risk factors involved in the pathogenesis of NAFLD, the dysbiotic gut microbiota plays an essential role, leading to low-grade chronic inflammation, oxidative stress, and production of various toxic metabolites. The intestinal microbiota is a dynamic ecosystem of microbes involved in the maintenance of physiological homeostasis; the alteration of its composition and function, during aging, is implicated in different liver diseases. Therefore, gut microbiota restoration might be a complementary approach for treating NAFLD. The administration of probiotics, which can relieve oxidative stress and elicit several anti-aging properties, could be a strategy to modify the composition and restore a healthy gut microbiota. Indeed, probiotics could represent a valid supplement to prevent and/or help treating some diseases, such as NAFLD, thus improving the already available pharmacological intervention. Moreover, in aging, intervention of prebiotics and fecal microbiota transplantation, as well as probiotics, will provide novel therapeutic approaches. However, the relevant research is limited, and several scientific research works need to be done in the near future to confirm their efficacy.

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Targeting lipophagy as a potential therapeutic strategy for nonalcoholic fatty liver disease

Cited by 25 publications

References 158 publications

Down-Regulating the High Level of 17-Beta-Hydroxysteroid Dehydrogenase 13 Plays a Therapeutic Role for Non-Alcoholic Fatty Liver Disease

Down-Regulating the High Level of 17-Beta-Hydroxysteroid Dehydrogenase 13 Plays a Therapeutic Role for Non-Alcoholic Fatty Liver Disease

Mechanism and Therapeutic Targets of c-Jun-N-Terminal Kinases Activation in Nonalcoholic Fatty Liver Disease

Age-Related NAFLD: The Use of Probiotics as a Supportive Therapeutic Intervention

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