The sodium-glucose cotransporter-2 inhibitor Tofogliflozin prevents the progression of nonalcoholic steatohepatitis–associated liver tumors in a novel murine model - 17/06/21

Doi : 10.1016/j.biopha.2021.111738

Naoki Yoshioka ^a,^d,^{^{1
Naoki Yoshioka and Miyako Tanaka contributed equally to this work.}}, Miyako Tanaka ^a,^e,^⁎,^{^{1
Naoki Yoshioka and Miyako Tanaka contributed equally to this work.}} , Kozue Ochi ^a, Akiko Watanabe ^a, Kenji Ono ^b,^f, Makoto Sawada ^b,^f, Tomoo Ogi ^c,^g, Michiko Itoh ^a,ⁱ, Ayaka Ito ^a,^e, Yukihiro Shiraki ^h, Atsushi Enomoto ^h, Masatoshi Ishigami ^d, Mitsuhiro Fujishiro ^d, Yoshihiro Ogawa ^a,^j, Takayoshi Suganami ^a,^e,^⁎
^a Department of Molecular Medicine and Metabolism, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan
^b Department of Brain Function, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan
^c Department of Genetics, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan
^d Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
^e Department of Immunometabolism, Nagoya University Graduate School of Medicine, Nagoya, Japan
^f Department of Molecular Pharmacokinetics, Nagoya University Graduate School of Medicine, Nagoya, Japan
^g Department of Human Genetics and Molecular Biology, Nagoya University Graduate School of Medicine, Nagoya, Japan
^h Department of Pathology, Nagoya University Graduate School of Medicine, Nagoya, Japan
ⁱ Kanagawa Institute of Industrial Science and Technology, Ebina, Japan
^j Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

^⁎Corresponding authors at: Department of Molecular Medicine and Metabolism, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan.Department of Molecular Medicine and Metabolism, Research Institute of Environmental Medicine, Nagoya UniversityNagoyaJapan

Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.

pages	12
Iconographies	6
Vidéos	0
Autres	0

Abstract

Background

Diabetes and obesity contribute to the pathogenesis of nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). However, how diabetes and obesity accelerate liver tumorigenesis remains to be fully understood. Moreover, to verify the therapeutic potential of anti-diabetic drugs, there exists a strong need for appropriate animal models that recapitulate human pathophysiology of NASH and HCC.

Methods

We established a novel murine model of NASH-associated liver tumors using genetically obese melanocortin 4 receptor-deficient mice fed on Western diet in combination with a chemical procarcinogen, and verified the validity of our model in evaluating drug efficacy.

Findings

Our model developed multiple liver tumors together with obesity, diabetes, and NASH within a relatively short period (approximately 3 months). In this model, sodium glucose cotransporter 2 inhibitor Tofogliflozin prevented the development of NASH-like liver phenotypes and the progression of liver tumors. Tofogliflozin attenuated p21 expression of hepatocytes in non-tumorous lesions in the liver.

Interpretation

Tofogliflozin treatment attenuates cellular senescence of hepatocytes under obese and diabetic conditions. This study provides a unique animal model of NASH-associated liver tumors, which is applicable for assessing drug efficacy to prevent or treat NASH-associated HCC.

Le texte complet de cet article est disponible en PDF.

Keywords : Diabetes, Nonalcoholic steatohepatitis, Hepatocellular carcinoma, Animal model, Sodium glucose cotransporter 2 inhibitor, Cellular senescence

Plan

Export

Vol 140

Article 111738- août 2021 Retour au numéro

Article précédent

Electroacupuncture facilitates M2 macrophage polarization and its potential role in the regulation of inflammatory response
Huai-Fu Wang, Li Chen, Ya Xie, Xiao-Fang Wang, Kun Yang, Ying Ning, Jia-Yue He, Wei-Jun Ding

| Article suivant

Thyme oil alleviates Ova-induced bronchial asthma through modulating Th2 cytokines, IgE, TSLP and ROS
Ayman M. Mousa, Ahmad Almatroudi, Ameen S. Alwashmi, Waleed Al Abdulmonem, Abdullah S.M. Aljohani, Fahad A. Alhumaydhi, Mohammed A. Alsahli, Faris Alrumaihi, Khaled S. Allemailem, Ahmed A.H. Abdellatif, Arif Khan, Masood A. Khan, Fahad M. Alshabrmi, Abdulmohsen Alruwetei, Mohammad Aljasir, Faris F. Aba alkhayl, Arshad H. Rahmani, Osamah Al Rugaie, Abdullah M. Alnuqaydan, Suliman A. Alsagaby, Fahad M. Aldakheel, Saleh A. Almatroodi

Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.

Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’achat d’article à l’unité est indisponible à l’heure actuelle.

Déjà abonné à cette revue ?

connectez-vous ou créez un compte

The sodium-glucose cotransporter-2 inhibitor Tofogliflozin prevents the progression of nonalcoholic steatohepatitis–associated liver tumors in a novel murine model - 17/06/21

Abstract

Background

Methods

Findings

Interpretation

Plan

Export citations

Fichier

Contenu

Accès rapides

Mon compte

Aide & support

Plateformes Elsevier Masson

Déclaration CNIL