Metformin Actions on the Liver: Protection Mechanisms Emerging in Hepatocytes and Immune Cells against NASH-Related HCC
Nonalcoholic fatty liver disease (NAFLD) is strongly linked to the global epidemic of obesity and type 2 diabetes mellitus (T2DM). Notably, NAFLD can progress from the mildest form of simple steatosis to nonalcoholic steatohepatitis (NASH) that increases the risk for hepatocellular carcinoma (HCC),...
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| Veröffentlicht in: | International journal of molecular sciences 2021-05, Vol.22 (9), p.5016 |
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| description | Nonalcoholic fatty liver disease (NAFLD) is strongly linked to the global epidemic of obesity and type 2 diabetes mellitus (T2DM). Notably, NAFLD can progress from the mildest form of simple steatosis to nonalcoholic steatohepatitis (NASH) that increases the risk for hepatocellular carcinoma (HCC), which is a malignancy with a dismal prognosis and rising incidence in the United States and other developed counties, possibly due to the epidemic of NAFLD. Metformin, the first-line drug for T2DM, has been suggested to reduce risks for several types of cancers including HCC and protect against NASH-related HCC, as revealed by epidemical studies on humans and preclinical studies on animal models. This review focuses on the pathogenesis of NASH-related HCC and the mechanisms by which metformin inhibits the initiation and progression of NASH-related HCC. Since the functional role of immune cells in liver homeostasis and pathogenesis is increasingly appreciated in developing anti-cancer therapies on liver malignancies, we discuss both the traditional targets of metformin in hepatocytes and the recently defined effects of metformin on immune cells. |
| doi_str_mv | 10.3390/ijms22095016 |
| format | Article |
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Notably, NAFLD can progress from the mildest form of simple steatosis to nonalcoholic steatohepatitis (NASH) that increases the risk for hepatocellular carcinoma (HCC), which is a malignancy with a dismal prognosis and rising incidence in the United States and other developed counties, possibly due to the epidemic of NAFLD. Metformin, the first-line drug for T2DM, has been suggested to reduce risks for several types of cancers including HCC and protect against NASH-related HCC, as revealed by epidemical studies on humans and preclinical studies on animal models. This review focuses on the pathogenesis of NASH-related HCC and the mechanisms by which metformin inhibits the initiation and progression of NASH-related HCC. Since the functional role of immune cells in liver homeostasis and pathogenesis is increasingly appreciated in developing anti-cancer therapies on liver malignancies, we discuss both the traditional targets of metformin in hepatocytes and the recently defined effects of metformin on immune cells.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms22095016</identifier><identifier>PMID: 34065108</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Animal models ; Antidiabetics ; Biopsy ; Clinical trials ; Diabetes ; Diabetes mellitus ; Diabetes mellitus (non-insulin dependent) ; Epidemics ; Fatty liver ; Glucose ; Hepatocellular carcinoma ; Hepatocytes ; Homeostasis ; Immune system ; Inflammation ; Insulin resistance ; Liver ; Liver cancer ; Liver diseases ; Malignancy ; Medical prognosis ; Metabolic syndrome ; Metabolites ; Metformin ; Mortality ; Obesity ; Pathogenesis ; Patients ; Review ; Steatosis ; Transplants & implants</subject><ispartof>International journal of molecular sciences, 2021-05, Vol.22 (9), p.5016</ispartof><rights>2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). 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Notably, NAFLD can progress from the mildest form of simple steatosis to nonalcoholic steatohepatitis (NASH) that increases the risk for hepatocellular carcinoma (HCC), which is a malignancy with a dismal prognosis and rising incidence in the United States and other developed counties, possibly due to the epidemic of NAFLD. Metformin, the first-line drug for T2DM, has been suggested to reduce risks for several types of cancers including HCC and protect against NASH-related HCC, as revealed by epidemical studies on humans and preclinical studies on animal models. This review focuses on the pathogenesis of NASH-related HCC and the mechanisms by which metformin inhibits the initiation and progression of NASH-related HCC. 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| subjects | Animal models Antidiabetics Biopsy Clinical trials Diabetes Diabetes mellitus Diabetes mellitus (non-insulin dependent) Epidemics Fatty liver Glucose Hepatocellular carcinoma Hepatocytes Homeostasis Immune system Inflammation Insulin resistance Liver Liver cancer Liver diseases Malignancy Medical prognosis Metabolic syndrome Metabolites Metformin Mortality Obesity Pathogenesis Patients Review Steatosis Transplants & implants |
| title | Metformin Actions on the Liver: Protection Mechanisms Emerging in Hepatocytes and Immune Cells against NASH-Related HCC |
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