Review
Biochemistry & Molecular Biology
Fiona M. Russell, David Grahame Hardie
Summary: AMP-activated protein kinase (AMPK) plays a crucial role in regulating cellular energy balance by promoting ATP production and inhibiting cell growth. It may restrain aberrant growth before tumorigenesis, but support the survival of cancer cells once cancer has arisen.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Kaitlin R. Morrison, Tingting Wang, Kuan Yoow Chan, Eleanor W. Trotter, Ari Gillespie, Michael Z. Michael, Jonathan S. Oakhill, Iain M. Hagan, Janni Petersen
Summary: The expression and activity of AMPK alpha 1 catalytic subunit are significantly associated with poor prognosis in colorectal cancer patients. By attenuating mTOR control of AMPK alpha 1, a mutant colorectal cancer cell line with elevated AMPK alpha 1 signaling was generated. This elevated signaling confers hypersensitivity to metformin-induced growth inhibition, suggesting a potential role for metformin in colorectal cancer therapy.
Article
Oncology
Kiyoaki Sugiura, Koji Okabayashi, Ryo Seishima, Takashi Ishida, Kohei Shigeta, Masashi Tsuruta, Hirotoshi Hasegawa, Yuko Kitagawa
Summary: Metformin, a commonly used drug for diabetes treatment, has been found to have anti-cancer effects in colorectal cancer. This study explores the underlying molecular mechanisms and finds that metformin inhibits colorectal cancer proliferation, migration, and invasion by activating the AMPK-mTOR pathway. In addition, metformin decreases liver metastasis and promotes apoptosis in metastatic liver tumors. These findings suggest that metformin could be a potential anti-metastatic treatment for colorectal cancer.
Review
Pharmacology & Pharmacy
Dorota Rogacka, Agnieszka Piwkowska
Summary: Podocytes and their foot processes are crucial for regulating glomerular permeability, with disturbances in podocyte function playing a central role in the development of proteinuria in diabetic nephropathy. Metformin, an oral antidiabetic agent, has potential beneficial effects on diabetic kidney function in addition to lowering glucose levels. Additionally, the activation of AMPK is a key mechanism of action of metformin in protecting against pathological changes in podocytes induced by hyperglycemia.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Jinxing Hu, Zeqi Zheng, Xuelian Li, Bingong Li, Xingjun Lai, Na Li, Shufang Lei
Summary: Metformin plays a role in reducing endothelial cell injury and suppressing endothelial-mesenchymal transition induced by hypoxia, by activating the AMPK pathway, increasing p-AMPK, and inhibiting mammalian target of rapamycin.
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
(2021)
Review
Geriatrics & Gerontology
Ming-Rui Du, Quan-You Gao, Chen-Lin Liu, Lin-Ya Bai, Tian Li, Fei-Long Wei
Summary: Metformin, as a first-line hypoglycemic drug, not only has proven hypoglycemic effects, but also exhibits cardioprotective, anti-inflammatory, and anticancer activities. It has been increasingly recognized for its potential in preventing and treating neurodegenerative diseases. Research suggests that metformin can prevent the progression of neurodegenerative diseases by regulating various cellular processes. However, there are also theories proposing a two-sided effect of metformin that may accelerate the progression of neurodegenerative diseases. This review examines both animal experiments and clinical studies to discuss the potential application of metformin in neurodegenerative diseases.
FRONTIERS IN AGING NEUROSCIENCE
(2022)
Article
Cell Biology
Malgorzata Tokarska-Schlattner, Laurence Kay, Pascale Perret, Raffaella Isola, Stephane Attia, Frederic Lamarche, Cindy Tellier, Cecile Cottet-Rousselle, Amjad Uneisi, Isabelle Hininger-Favier, Marc Foretz, Herve Dubouchaud, Catherine Ghezzi, Christian Zuppinger, Benoit Viollet, Uwe Schlattner
Summary: AMPK, a key regulator of energy homeostasis, plays important roles in maintaining cardiac function under increased workload conditions. Deletion of AMPK genes in cardiomyocytes did not affect heart function under physiological conditions, but led to alterations in response to increased workload. AMPK deletion also resulted in decreased basal metabolic rate and locomotor activity, along with changes in cardiac mitochondrial function and bioenergetics.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Masahiro Takahara, Akinobu Takaki, Sakiko Hiraoka, Kensuke Takei, Eriko Yasutomi, Shoko Igawa, Shumpei Yamamoto, Shohei Oka, Masayasu Ohmori, Yasushi Yamasaki, Toshihiro Inokuchi, Hideaki Kinugasa, Keita Harada, Heiichiro Udono, Hiroyuki Okada
Summary: Metformin, a drug commonly used for type 2 diabetes, has been found to suppress intestinal inflammation and improve inflammatory bowel disease (IBD) by activating AMP-activated protein kinase (AMPK). This study suggests that AMPK may be a key molecule in regulating mucosal immunity and inflammation, and AMPK-activating drugs like metformin could be potential therapeutic agents for the treatment of IBD.
Review
Genetics & Heredity
Sanjay Goel, Ravinder Singh, Varinder Singh, Harmanjit Singh, Pratima Kumari, Hitesh Chopra, Rohit Sharma, Eugenie Nepovimova, Martin Valis, Kamil Kuca, Talha Bin Emran
Summary: Metformin, a plant-based drug, is used to treat type-2 diabetes and has diverse effects on the human body. It activates the AMPK pathway and also has other mechanisms to produce beneficial effects. Its potential for treating diseases beyond diabetes is of great importance.
FRONTIERS IN GENETICS
(2022)
Article
Veterinary Sciences
Xu-Yang Gao, Bu-Hao Deng, Xin-Rui Li, Yu Wang, Jian-Xin Zhang, Xiao-Yan Hao, Jun-Xing Zhao
Summary: The study found that melatonin enhances the formation of sheep brown adipocytes by activating AMPKα1, reducing lamb mortality and economic losses.
FRONTIERS IN VETERINARY SCIENCE
(2021)
Article
Pharmacology & Pharmacy
Kai Lou, Pei Sun, Chunxue Zhang, Qiang Jiang, Shuguang Pang
Summary: Accumulating evidence has shown that metformin improves hypertriglyceridemia by regulating DGAT2 and XBP1 expression in the liver, through activation of AMPK. These findings suggest that XBP1 may be a new metabolic mediator for metformin treatment of hypertriglyceridemia and associated metabolic diseases.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Zhongling Zhu, Teng Jiang, Huirong Suo, Shan Xu, Cai Zhang, Guoguang Ying, Zhao Yan
Summary: The study found that metformin can enhance the anti-proliferative effect of anlotinib in NSCLC cells by activating AMPK and inhibiting mTOR, inducing apoptosis and oxidative stress, thus increasing the sensitivity of NSCLC cells to the anticancer drug.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yiguang Lin, Huijun Ji, Xiaocong Cao, Yongjie Cen, Yumei Chen, Shuangshun Ji, Sichun Zheng
Summary: Insecticides are commonly used to control the serious pest Nilaparvata lugens in rice fields, but their repeated application can have negative effects. A study found that AMP-activated protein kinase (AMPK) plays a crucial role in maintaining energy metabolism and responding to insecticide treatment in N. lugens. Knockdown of NlAMPK alpha significantly enhanced the insecticidal efficiency of pymetrozine against N. lugens.
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
(2021)
Article
Physiology
Xia Dong, Tiankun Hui, Jie Chen, Zheng Yu, Dongyan Ren, Suqi Zou, Shunqi Wang, Erkang Fei, Huifeng Jiao, Xinsheng Lai
Summary: Metformin treatment improves muscle function and diminishes neuromuscular deficits in mdx mice, suggesting its potential use as a therapeutic drug in DMD patients.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Respiratory System
Dong Tian, Xiangyun Zheng, Hongtao Tang, Heng Huang, Junjie Wang, Lin Xu, Caihan Li, Haoji Yan, Ruixuan Yu, Jinzhu Nan, Menggen Liu, Xiaoguang Guo, Shunhai Jian, Tao Wang, Senyi Deng, Qiang Pu, Lunxu Liu
Summary: Metformin, an oral hypoglycemic agent, attenuates chronic lung allograft dysfunction (CLAD) in rat models through its antifibrotic and immunomodulatory effects. The activation of AMPK may play a role in the mechanism. These findings provide experimental rationale for further clinical trials.
RESPIRATORY RESEARCH
(2023)
Article
Multidisciplinary Sciences
Claudie Bosc, Nicolas Broin, Marjorie Fanjul, Estelle Saland, Thomas Farge, Charly Courdy, Aurelie Batut, Rawand Masoud, Clement Larrue, Sarah Skuli, Nicolas Espagnolle, Jean-Christophe Pages, Alice Carrier, Frederic Bost, Justine Bertrand-Michel, Jerome Tamburini, Christian Recher, Sarah Bertoli, Veronique Mansat-De Mas, Stephane Manenti, Jean-Emmanuel Sarry, Carine Joffre
NATURE COMMUNICATIONS
(2020)
Article
Cell Biology
Emilie Jaune, Elisa Cavazza, Cyril Ronco, Oleksandr Grytsai, Patricia Abbe, Nedra Tekaya, Marwa Zerhouni, Guillaume Beranger, Lisa Kaminski, Frederic Bost, Maeva Gesson, Meri Tulic, Paul Hofman, Robert Ballotti, Thierry Passeron, Thomas Botton, Rachid Benhida, Stephane Rocchi
Summary: The compound CRO15 shows promising anti-melanoma effects by acting on melanoma cells through two distinct mechanisms, leading to cell death. This compound has potential in reducing the growth of melanoma xenografts sensitive or resistant to BRAF inhibitors.
CELL DEATH & DISEASE
(2021)
Article
Neurosciences
Nirvana Sadaghianloo, Julie Contenti, Serge Declemy, Damien Ambrosetti, Masa Zdralevic, Mounia Tannour-Louet, Lucilla Fabbri, Gilles Pages, Frederic Bost, Reda Hassen-Khodja, Jacques Pouyssegur, Elixene Jean-Baptiste, Alan Dardik, Nathalie M. Mazure
Summary: Patients with end-stage renal failure need AVFs for dialysis, but these AVFs often fail due to excessive venous thickness. This study found that venous cells adapt their metabolism depending on oxygen concentration, and targeting the hypoxic response pathway with drugs can help decrease excessive venous thickness. In a mouse model, inhibiting HIFs decreased neointimal hyperplasia, suggesting that drugs targeting HIFs could prevent AVF failure.
JOURNAL OF PHYSIOLOGY-LONDON
(2021)
Article
Plant Sciences
Farah Drissi, Farid Lahfa, Teresa Gonzalez, Franck Peiretti, Jean-Francois Tanti, Mohamed Haddad, Nicolas Fabre, Roland Govers
Summary: The study shows that Citrullus colocynthis fruit has insulin-enhancing effects, which may partly explain its antidiabetic effects in traditional medicine.
JOURNAL OF ETHNOPHARMACOLOGY
(2021)
Article
Cell Biology
Marc Cougnon, Romain Carcy, Nicolas Melis, Isabelle Rubera, Christophe Duranton, Karine Dumas, Jean-Francois Tanti, Catherine Pons, Nicolas Soubeiran, Marina Shkreli, Thierry Hauet, Luc Pellerin, Sebastien Giraud, Nicolas Blondeau, Michel Tauc, Didier F. Pisani
Summary: Inhibition of eukaryotic initiation factor 5A activation by GC7 protects kidney cells from ischemic damage by altering their energy source and oxygen dependence, making them independent of oxygen supply.
CELL DEATH & DISEASE
(2021)
Article
Biology
Stephanie Torrino, Victor Tiroille, Bastien Dolfi, Maeva Dufies, Charlotte Hinault, Laurent Bonesso, Sonia Dagnino, Jennifer Uhler, Marie Irondelle, Anne-sophie Gay, Lucile Fleuriot, Delphine Debayle, Sandra Lacas-Gervais, Mireille Cormont, Thomas Bertero, Frederic Bost, Jerome Gilleron, Stephan Clavel
Summary: UBTD1 plays a crucial role in EGFR signaling by controlling both the phosphorylation and lysosomal degradation of EGFR, contributing to the regulation of signal duration.
Article
Multidisciplinary Sciences
Jennifer Jager, Melanie Gaudfrin, Jerome Gilleron, Mireille Cormont, Jean-Francois Tanti
Summary: This study presents a protocol for differentiating murine fibroblasts into mature adipocytes and modulating the expression of proteins and micro-RNAs in these adipocytes through reverse-transfection.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2021)
Article
Oncology
Marc Pujalte Martin, Delphine Borchiellini, Brice Thamphya, Aline Guillot, Jean-Baptiste Paoli, Dominique Besson, Werner Hilgers, Frank Priou, Claude El Kouri, Benjamin Hoch, Jean-Laurent Deville, Renaud Schiappa, Sandrine Cheli, Gerard Milano, Jean-Francois Tanti, Frederic Bost, Jean-Marc Ferrero
Summary: In mCRPC patients, the addition of MET did not improve the standard DOCE regimen, although there were some trends in certain indicators. Therefore, further research targeting tumor cell metabolism should be conducted.
CLINICAL GENITOURINARY CANCER
(2021)
Review
Endocrinology & Metabolism
Emma Bokobza, Charlotte Hinault, Victor Tiroille, Stephan Clavel, Frederic Bost, Nicolas Chevalier
Summary: Obesity is a significant public health concern associated with increased risk of various cancers, including gastrointestinal tract cancers and hormone-dependent cancers. Adipose tissue plays a crucial role in this process, as it is considered a major internal source of endocrine disrupting chemicals that can impact hormonal balance and cell proliferation.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Cell Biology
Simona Cataldi, Marianna Aprile, Daniela Melillo, Ines Mucel, Sophie Giorgetti-Peraldi, Mireille Cormont, Paola Italiani, Matthias Blueher, Jean-Francois Tanti, Alfredo Ciccodicola, Valerio Costa
Summary: In this study, it was found that inflammatory factors secreted by metabolically-activated macrophages can modulate the expression and splicing of PPARG, leading to impaired adipocyte differentiation and exacerbating the defective PPAR gamma activity in hypertrophic adipose tissue.
Article
Pathology
Mathieu Roumiguie, David Esteve, Cecile Manceau, Aurelie Toulet, Jerome Gilleron, Chloe Belles, Yiyue Jia, Cynthia Houel, Sarah Pericart, Sophie LeGonidec, Philippe Valet, Mireille Cormont, Jean-Francois Tanti, Bernard Malavaud, Anne Bouloumie, Delphine Milhas, Catherine Muller
Summary: This study characterized the structural and functional features of periprostatic adipose tissue (PPAT) and found that it has a sparse vascular network compared to abdominopelvic adipose tissue (APAT), suggesting hypoxia in PPAT. The gene expression analysis revealed high levels of hypoxia-related genes in PPAT, confirming its adaptive response to hypoxia. This chronic hypoxic state is associated with inflammation and fibrosis, explaining why PPAT does not expand in obesity.
AMERICAN JOURNAL OF PATHOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Aurelie Charazac, Charlotte Hinault, Bastien Dolfi, Solene Hautier, Celia Deconde Le Butor, Frederic Bost, Nicolas Chevalier
Summary: Endocrine Disrupting Compounds (EDCs) are compounds found in everyday products that can disrupt hormonal effects and have adverse health effects. This study found that four specific EDCs promoted the proliferation of cancer cell lines from hormone-sensitive organs (prostate and breast), with PFOA and PCB153 showing this effect at very low concentrations (10(-12) M).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Pierre-Jean Cornejo, Bastien Vergoni, Mickael Ohanna, Brice Angot, Teresa Gonzalez, Jennifer Jager, Jean-Francois Tanti, Mireille Cormont
Summary: This study identifies miR-34a as a new mediator of adipocyte insulin resistance. Upregulation of miR-34a inhibits insulin signaling and decreases glucose transport, accompanied by a reduced expression of VAMP2 and an increased expression of PTP1B. Mechanistically, miR-34a decreases NAD(+) levels, thereby inhibiting Sirtuin-1 and promoting the upregulation of PTP1B. The mRNA expression of Nampt and Naprt is also decreased in adipose tissue of obese mice.
Review
Biochemistry & Molecular Biology
Charlotte Hinault, Philippe Caroli-Bosc, Frederic Bost, Nicolas Chevalier
Summary: Diabetes mellitus is a significant global health problem, impacting individuals and economies. The chronic hyperglycemia associated with diabetes leads to severe complications, including retinopathy, kidney failure, and cardiovascular diseases. While genetic factors and environmental factors like sedentary lifestyles, overweight, and obesity contribute to the development of diabetes, there is growing evidence suggesting the role of endocrine-disrupting chemicals (EDCs) in the pathophysiology of diabetes and metabolic disorders. This narrative review critically examines the impact of EDCs on our endocrine system and their link to diabetes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)