Metformin Actions on the Liver: Protection Mechanisms Emerging in Hepatocytes and Immune Cells against NASH-Related HCC

A combination of herbal compound (SPTC) along with exercise or metformin more efficiently alleviated diabetic complications through down-regulation of stress oxidative pathway upon activating Nrf2-Keap1 axis in AGE rich diet-induced type 2 diabetic mice

(2021) Golbarg Rahimi et al.   Nutrition & Metabolism

Boosting anti-PD-1 therapy with metformin-loaded macrophage-derived microparticles

(2021) Zhaohan Wei et al.   Nature Communications

An AMPK–caspase-6 axis controls liver damage in nonalcoholic steatohepatitis

(2020) Peng Zhao et al.   SCIENCE

Liver macrophages inhibit the endogenous antioxidant response in obesity-associated insulin resistance

(2020) Valerio Azzimato et al.   Science Translational Medicine

Hepatocyte Injury and Hepatic Stem Cell Niche in the Progression of Non-Alcoholic Steatohepatitis

(2020) Diletta Overi et al.   Cells

Is there an association between commonly employed biomarkers of liver fibrosis and liver stiffness in the general population?

(2020) Francesco Giuseppe Foschi et al.   Annals of Hepatology

Annual report to the nation on the status of cancer, part I: National cancer statistics

(2020) S. Jane Henley et al.   CANCER

Type 2 Diabetes and Metformin Use Associate With Outcomes of Patients With Non-alcoholic Steatohepatitis-related, Child-Pugh A Cirrhosis

(2020) Eduardo Vilar-Gomez et al.   Clinical Gastroenterology and Hepatology

Metformin Enhances the Antitumor Activity of CD8+ T Lymphocytes via the AMPK–miR-107–Eomes–PD-1 Pathway

(2020) Zhen Zhang et al.   JOURNAL OF IMMUNOLOGY

FBP1 loss disrupts liver metabolism and promotes tumorigenesis through a hepatic stellate cell senescence secretome

(2020) Fuming Li et al.   NATURE CELL BIOLOGY

NCOA5 deficiency promotes a unique liver protumorigenic microenvironment through p21WAF1/CIP1 overexpression, which is reversed by metformin

(2020) Mark Williams et al.   ONCOGENE

Macrophage Subsets in Obesity, Aligning the Liver and Adipose Tissue

(2020) Anneleen Remmerie et al.   Frontiers in Endocrinology

Immunological distinctions between nonalcoholic steatohepatitis and hepatocellular carcinoma

(2020) Seo-Young Koo et al.   EXPERIMENTAL AND MOLECULAR MEDICINE

Optimization of Point-Shear Wave Elastography by Skin-to-Liver Distance to Assess Liver Fibrosis in Patients Undergoing Bariatric Surgery

(2020) Mauro Giuffrè et al.   Diagnostics

Metformin reverses chemoresistance in non-small cell lung cancer via accelerating ubiquitination-mediated degradation of Nrf2

(2020) Sha Huang et al.   Translational Lung Cancer Research

Landscape of infiltrating B cells and their clinical significance in human hepatocellular carcinoma

(2019) Zhao Zhang et al.   OncoImmunology

Metformin delays AKT/c-Met-driven hepatocarcinogenesis by regulating signaling pathways for de novo lipogenesis and ATP generation

(2019) Cong Zhang et al.   TOXICOLOGY AND APPLIED PHARMACOLOGY

AMPK activation inhibits the functions of myeloid-derived suppressor cells (MDSC): impact on cancer and aging

(2019) Antero Salminen et al.   JOURNAL OF MOLECULAR MEDICINE-JMM

The Role of AMP-Activated Protein Kinase as a Potential Target of Treatment of Hepatocellular Carcinoma

(2019) Xue Jiang et al.   Cancers

Long-term metformin use may improve clinical outcomes in diabetic patients with non-alcoholic steatohepatitis and bridging fibrosis or compensated cirrhosis

(2019) Eduardo Vilar-Gomez et al.   ALIMENTARY PHARMACOLOGY & THERAPEUTICS

Combination of metformin and luteolin synergistically protects carbon tetrachloride‐induced hepatotoxicity: Mechanism involves antioxidant, anti‐inflammatory, antiapoptotic, and Nrf2/HO‐1 signaling pathway

(2019) Yang Yan et al.   BIOFACTORS

Hepatic Natural Killer Cells: Organ-Specific Sentinels of Liver Immune Homeostasis and Physiopathology

(2019) Joanna Mikulak et al.   Frontiers in Immunology

The TNF Paradox in Cancer Progression and Immunotherapy

(2019) Anne Montfort et al.   Frontiers in Immunology

Retained NK Cell Phenotype and Functionality in Non-alcoholic Fatty Liver Disease

(2019) Natalie Stiglund et al.   Frontiers in Immunology

Obesity and liver cancer

(2019) Carlo Saitta et al.   Annals of Hepatology

Understanding the glucoregulatory mechanisms of metformin in type 2 diabetes mellitus

(2019) Marc Foretz et al.   Nature Reviews Endocrinology

Metformin in the prevention of hepatocellular carcinoma in diabetic patients: A systematic review

(2019) Victor Cunha et al.   Annals of Hepatology

Sustained ER stress promotes hyperglycemia by increasing glucagon action through the deubiquitinating enzyme USP14

(2019) Bin Liu et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Targeting Cyclic AMP Signalling in Hepatocellular Carcinoma

(2019) Mara Massimi et al.   Cells

Metformin inhibits the function of granulocytic myeloid-derived suppressor cells in tumor-bearing mice

(2019) Peiqi Xu et al.   BIOMEDICINE & PHARMACOTHERAPY

Tim-3 hampers tumor surveillance of liver resident and conventional NK cells by disrupting PI3K signaling

(2019) Siyu Tan et al.   CANCER RESEARCH

Metformin-Induced Reduction of CD39 and CD73 Blocks Myeloid-Derived Suppressor Cell Activity in Patients with Ovarian Cancer

(2018) Lifeng Li et al.   CANCER RESEARCH

NRF2 addiction in cancer cells

(2018) Hiroshi Kitamura et al.   CANCER SCIENCE

Nonalcoholic Fatty Liver Disease as a Nexus of Metabolic and Hepatic Diseases

(2018) Varman T. Samuel et al.   Cell Metabolism

New Aspects of Lipotoxicity in Nonalcoholic Steatohepatitis

(2018) Nahum Mendez-Sanchez et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Metformin and risk of hepatocellular carcinoma in patients with type 2 diabetes

(2018) Chin-Hsiao Tseng   LIVER INTERNATIONAL

Mechanisms of NAFLD development and therapeutic strategies

(2018) Scott L. Friedman et al.   NATURE MEDICINE

Metformin inhibits gluconeogenesis via a redox-dependent mechanism in vivo

(2018) Anila K. Madiraju et al.   NATURE MEDICINE

Metformin sensitizes endometrial cancer cells to chemotherapy through IDH1-induced Nrf2 expression via an epigenetic mechanism

(2018) Mingzhu Bai et al.   ONCOGENE

Predictive and preventive significance of AMPK activation on hepatocarcinogenesis in patients with liver cirrhosis

(2018) Xiaoli Yang et al.   Cell Death & Disease

Metformin blocks myeloid-derived suppressor cell accumulation through AMPK-DACH1-CXCL1 axis

(2018) Guohui Qin et al.   OncoImmunology

AMPK Re-Activation Suppresses Hepatic Steatosis but its Downregulation Does Not Promote Fatty Liver Development

(2018) Nadia Boudaba et al.   EBioMedicine

Metformin Promotes Antitumor Immunity via Endoplasmic-Reticulum-Associated Degradation of PD-L1

(2018) Jong-Ho Cha et al.   MOLECULAR CELL

Metformin reduces liver glucose production by inhibition of fructose-1-6-bisphosphatase

(2018) Roger W. Hunter et al.   NATURE MEDICINE

Metformin reverses the resistance mechanism of lung adenocarcinoma cells that knocks down the Nrf2 gene

(2018) Jiacui Zhang et al.   Oncology Letters

Risk of Hepatocellular Cancer in Patients With Non-Alcoholic Fatty Liver Disease

(2018) Fasiha Kanwal et al.   GASTROENTEROLOGY

Dietary Lipids Differentially Shape NASH Progression and the Transcriptome of Kupffer Cells and Infiltrating Macrophages

(2018) Brett McGettigan et al.   HEPATOLOGY

Metformin modulates innate immune-mediated inflammation and early progression of NAFLD-associated hepatocellular carcinoma in zebrafish

(2018) Sofia de Oliveira et al.   JOURNAL OF HEPATOLOGY

Dysregulation of Nrf2 in Hepatocellular Carcinoma: Role in Cancer Progression and Chemoresistance

(2018) Azhwar Raghunath et al.   Cancers

Insulin Receptor Isoforms in Physiology and Disease: An Updated View

(2017) Antonino Belfiore et al.   ENDOCRINE REVIEWS

Liver Cancer Cell of Origin, Molecular Class, and Effects on Patient Prognosis

(2017) Daniela Sia et al.   GASTROENTEROLOGY

Hepatoma-intrinsic CCRK inhibition diminishes myeloid-derived suppressor cell immunosuppression and enhances immune-checkpoint blockade efficacy

(2017) Jingying Zhou et al.   GUT

The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases

(2017) Naga Chalasani et al.   HEPATOLOGY

Metformin Sensitizes Non-small Cell Lung Cancer Cells to an Epigallocatechin-3-Gallate (EGCG) Treatment by Suppressing the Nrf2/HO-1 Signaling Pathway

(2017) Chenxiao Yu et al.   International Journal of Biological Sciences

Change in the Treg/Th17 cell imbalance in hepatocellular carcinoma patients and its clinical value

(2017) Yong-Ting Lan et al.   MEDICINE

Meta-analysis of studies using metformin as a reducer for liver cancer risk in diabetic patients

(2017) Shujuan Ma et al.   MEDICINE

Inflammation-induced IgA+ cells dismantle anti-liver cancer immunity

(2017) Shabnam Shalapour et al.   NATURE

Metformin-treated cancer cells modulate macrophage polarization through AMPK-NF-κB signaling

(2017) Chi-Fu Chiang et al.   Oncotarget

Tumor-infiltrating B cells producing antitumor active immunoglobulins in resected HCC prolong patient survival

(2017) Stefan M. Brunner et al.   Oncotarget

Diabetes Mellitus and Risk of Hepatocellular Carcinoma

(2017) Xu Li et al.   Biomed Research International

Immunoregulatory Role of NK Cells in Tissue Inflammation and Regeneration

(2017) Annie Tosello-Trampont et al.   Frontiers in Immunology

NK Cell Exhaustion

(2017) Jiacheng Bi et al.   Frontiers in Immunology

Role of Nrf2 and protective effects of Metformin against tobacco smoke-induced cerebrovascular toxicity

(2017) Shikha Prasad et al.   Redox Biology

Attenuation of CD4 + CD25 + Regulatory T Cells in the Tumor Microenvironment by Metformin, a Type 2 Diabetes Drug

(2017) Yuki Kunisada et al.   EBioMedicine

Liver biopsy in type 2 diabetes mellitus: Steatohepatitis represents the sole feature of liver damage

(2017) Mario Masarone et al.   PLoS One

Metformin prevents hepatocellular carcinoma development by suppressing hepatic progenitor cell activation in a rat model of cirrhosis

(2016) Danielle K. DePeralta et al.   CANCER

Loss of FBP1 facilitates aggressive features of hepatocellular carcinoma cells through the Warburg effect

(2016) Juan Yang et al.   CARCINOGENESIS

Metformin Activates AMPK through the Lysosomal Pathway

(2016) Chen-Song Zhang et al.   Cell Metabolism

Hepatocellular Carcinoma in the Absence of Cirrhosis in United States Veterans Is Associated With Nonalcoholic Fatty Liver Disease

(2016) Sahil Mittal et al.   Clinical Gastroenterology and Hepatology

Interleukin-15-mediated inflammation promotes non-alcoholic fatty liver disease

(2016) Yuneivy Cepero-Donates et al.   CYTOKINE

Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes

(2016) Zobair M. Younossi et al.   HEPATOLOGY

NKp46+ natural killer cells attenuate metabolism-induced hepatic fibrosis by regulating macrophage activation in mice

(2016) Annie-Carole Tosello-Trampont et al.   HEPATOLOGY

The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD)

(2016) Elena Buzzetti et al.   METABOLISM-CLINICAL AND EXPERIMENTAL

AMPK Facilitates Nuclear Accumulation of Nrf2 by Phosphorylating at Serine 550

(2016) Min Sung Joo et al.   MOLECULAR AND CELLULAR BIOLOGY

NAFLD causes selective CD4+ T lymphocyte loss and promotes hepatocarcinogenesis

(2016) Chi Ma et al.   NATURE

FASN regulates cellular response to genotoxic treatments by increasing PARP-1 expression and DNA repair activity via NF-κB and SP1

(2016) Xi Wu et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Dendritic cell-elicited B-cell activation fosters immune privilege via IL-10 signals in hepatocellular carcinoma

(2016) Fang-Zhu Ouyang et al.   Nature Communications

PD-1hi Identifies a Novel Regulatory B-cell Population in Human Hepatoma That Promotes Disease Progression

(2016) X. Xiao et al.   Cancer Discovery

Genomic Characterization of Metformin Hepatic Response

(2016) Marcelo R. Luizon et al.   PLoS Genetics

Impact of myeloid-derived suppressor cell on Kupffer cells from mouse livers with hepatocellular carcinoma

(2016) Stéphanie Lacotte et al.   OncoImmunology

Hepatocellular carcinoma is accelerated by NASH involving M2 macrophage polarization mediated by hif-1αinduced IL-10

(2016) Aditya Ambade et al.   OncoImmunology

Bile Acids and Dysbiosis in Non-Alcoholic Fatty Liver Disease

(2016) Marialena Mouzaki et al.   PLoS One

Fibrosis Progression in Nonalcoholic Fatty Liver vs Nonalcoholic Steatohepatitis: A Systematic Review and Meta-analysis of Paired-Biopsy Studies

(2015) Siddharth Singh et al.   Clinical Gastroenterology and Hepatology

Energy metabolism determines the sensitivity of human hepatocellular carcinoma cells to mitochondrial inhibitors and biguanide drugs

(2015) CHIA-CHI HSU et al.   ONCOLOGY REPORTS

Immune-mediated antitumor effect by type 2 diabetes drug, metformin

(2015) Shingo Eikawa et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Ceramides – Lipotoxic Inducers of Metabolic Disorders

(2015) Bhagirath Chaurasia et al.   TRENDS IN ENDOCRINOLOGY AND METABOLISM

Metformin increases antitumor activity of MEK inhibitors through GLI1 downregulation in LKB1 positive human NSCLC cancer cells

(2015) Carminia Maria Della Corte et al.   Oncotarget

Metformin prevents cancer metastasis by inhibiting M2-like polarization of tumor associated macrophages

(2015) Ling Ding et al.   Oncotarget

Metformin Antagonizes Cancer Cell Proliferation by Suppressing Mitochondrial-Dependent Biosynthesis

(2015) Takla Griss et al.   PLOS BIOLOGY

Metformin Inhibits Monocyte-to-Macrophage Differentiation via AMPK-Mediated Inhibition of STAT3 Activation: Potential Role in Atherosclerosis

(2015) Sathish Babu Vasamsetti et al.   DIABETES

Insulin inhibits AMPK activity and phosphorylates AMPK Ser485/491 through Akt in hepatocytes, myotubes and incubated rat skeletal muscle

(2014) Rudy J. Valentine et al.   ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS

Metabolic Activation of Intrahepatic CD8+ T Cells and NKT Cells Causes Nonalcoholic Steatohepatitis and Liver Cancer via Cross-Talk with Hepatocytes

(2014) Monika Julia Wolf et al.   CANCER CELL

Depletion of Carcinoma-Associated Fibroblasts and Fibrosis Induces Immunosuppression and Accelerates Pancreas Cancer with Reduced Survival

(2014) Berna C. Özdemir et al.   CANCER CELL

Stromal Elements Act to Restrain, Rather Than Support, Pancreatic Ductal Adenocarcinoma

(2014) Andrew D. Rhim et al.   CANCER CELL

NK cell receptor imbalance and NK cell dysfunction in HBV infection and hepatocellular carcinoma

(2014) Cheng Sun et al.   Cellular & Molecular Immunology

DNA-PK--A Candidate Driver of Hepatocarcinogenesis and Tissue Biomarker That Predicts Response to Treatment and Survival

(2014) L. Cornell et al.   CLINICAL CANCER RESEARCH

Diagnosis and classification of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis: Current concepts and remaining challenges

(2014) Etsuko Hashimoto et al.   HEPATOLOGY RESEARCH

Macrophages, Immunity, and Metabolic Disease

(2014) Joanne C. McNelis et al.   IMMUNITY

Metformin decreases IL-22 secretion to suppress tumor growth in an orthotopic mouse model of hepatocellular carcinoma

(2014) Dong Zhao et al.   INTERNATIONAL JOURNAL OF CANCER

Metformin Suppresses Lipopolysaccharide (LPS)-induced Inflammatory Response in Murine Macrophages via Activating Transcription Factor-3 (ATF-3) Induction

(2014) Juyoung Kim et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Serum immunoglobulin levels predict fibrosis in patients with non-alcoholic fatty liver disease

(2014) Stuart McPherson et al.   JOURNAL OF HEPATOLOGY

Metformin Attenuates Experimental Autoimmune Arthritis through Reciprocal Regulation of Th17/Treg Balance and Osteoclastogenesis

(2014) Hye-Jin Son et al.   MEDIATORS OF INFLAMMATION

Metformin inhibits mitochondrial complex I of cancer cells to reduce tumorigenesis

(2014) William W Wheaton et al.   eLife

NCOA5 Haploinsufficiency Results in Glucose Intolerance and Subsequent Hepatocellular Carcinoma

(2013) Shenglan Gao et al.   CANCER CELL

Prognostic Significance of AMPK Activation and Therapeutic Effects of Metformin in Hepatocellular Carcinoma

(2013) L. Zheng et al.   CLINICAL CANCER RESEARCH

Increased hepatic oxidative DNA damage in patients with nonalcoholic steatohepatitis who develop hepatocellular carcinoma

(2013) Shingo Tanaka et al.   JOURNAL OF GASTROENTEROLOGY

Biguanides suppress hepatic glucagon signalling by decreasing production of cyclic AMP

(2013) Russell A. Miller et al.   NATURE

Single phosphorylation sites in Acc1 and Acc2 regulate lipid homeostasis and the insulin-sensitizing effects of metformin

(2013) Morgan D Fullerton et al.   NATURE MEDICINE

Metformin Is Associated With Survival Benefit in Cancer Patients With Concurrent Type 2 Diabetes: A Systematic Review and Meta-Analysis

(2013) M. Yin et al.   ONCOLOGIST

B cells promote inflammation in obesity and type 2 diabetes through regulation of T-cell function and an inflammatory cytokine profile

(2013) J. DeFuria et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Metformin inhibits heme oxygenase-1 expression in cancer cells through inactivation of Raf-ERK-Nrf2 signaling and AMPK-independent pathways

(2013) Minh Truong Do et al.   TOXICOLOGY AND APPLIED PHARMACOLOGY

Association Between Nonalcoholic Fatty Liver Disease and Risk for Hepatocellular Cancer, Based on Systematic Review

(2012) Donna L. White et al.   Clinical Gastroenterology and Hepatology

Inhibition of natural killer cells protects the liver against acute injury in the absence of glycine N-methyltransferase

(2012) Laura Gomez-Santos et al.   HEPATOLOGY

The Inflammasome NLRs in Immunity, Inflammation, and Associated Diseases

(2011) Beckley K. Davis et al.   Annual Review of Immunology

Interleukin-17 exacerbates hepatic steatosis and inflammation in non-alcoholic fatty liver disease

(2011) Y. Tang et al.   CLINICAL AND EXPERIMENTAL IMMUNOLOGY

Interleukin-22 promotes human hepatocellular carcinoma by activation of STAT3

(2011) Runqiu Jiang et al.   HEPATOLOGY

Impact of Metformin on the Prognosis of Cirrhosis Induced by Viral Hepatitis C in Diabetic Patients

(2011) Gisèle Nkontchou et al.   JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM

Decreased nucleotide excision repair in steatotic livers associates with myeloperoxidase-immunoreactivity

(2011) Marten A. Schults et al.   MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS

Hepatic steatosis: a role for de novo lipogenesis and the transcription factor SREBP-1c

(2010) P. Ferré et al.   DIABETES OBESITY & METABOLISM

Involvement of Th17 and Th1 Effector Responses in Patients with Hepatitis B

(2010) Yufu Ye et al.   JOURNAL OF CLINICAL IMMUNOLOGY

Myeloid derived suppressor cells inhibit natural killer cells in patients with hepatocellular carcinoma via the NKp30 receptor

(2009) Bastian Hoechst et al.   HEPATOLOGY

Autoimmunity and oxidatively modified autoantigens

(2008) Biji T. Kurien et al.   AUTOIMMUNITY REVIEWS