Trehalose Activates Hepatic and Myocardial Autophagy and Has Anti-Inflammatory Effects in <i>db</i>/<i>db</i> Diabetic Mice
Tatiana A. Korolenko,
Marina V. Ovsyukova,
Nataliya P. Bgatova,
Igor D. Ivanov,
Svetlana I. Makarova,
Valentin A. Vavilin,
Alexey V. Popov,
Ekaterina I. Yuzhik,
Elena V. Koldysheva,
Erik C. Korolenko,
Evgeny L. Zavjalov,
Tamara G. Amstislavskaya
Affiliations
Tatiana A. Korolenko
Scientific-Research Institute of Neurosciences and Medicine, Timakov Street 4, 630117 Novosibirsk, Russia
Marina V. Ovsyukova
Scientific-Research Institute of Neurosciences and Medicine, Timakov Street 4, 630117 Novosibirsk, Russia
Nataliya P. Bgatova
Laboratory of Ultrastructural Research, Research Institute of Clinical and Experimental Lymphology—Branch of Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630060 Novosibirsk, Russia
Igor D. Ivanov
Laboratory of Drug Metabolism and Pharmacokinetics, Federal Research Center of Fundamental and Translational Medicine, Institute of Molecular Biology and Biophysics, Timakov Street 2, 630117 Novosibirsk, Russia
Svetlana I. Makarova
Laboratory of Drug Metabolism and Pharmacokinetics, Federal Research Center of Fundamental and Translational Medicine, Institute of Molecular Biology and Biophysics, Timakov Street 2, 630117 Novosibirsk, Russia
Valentin A. Vavilin
Laboratory of Drug Metabolism and Pharmacokinetics, Federal Research Center of Fundamental and Translational Medicine, Institute of Molecular Biology and Biophysics, Timakov Street 2, 630117 Novosibirsk, Russia
Alexey V. Popov
Laboratory of Drug Metabolism and Pharmacokinetics, Federal Research Center of Fundamental and Translational Medicine, Institute of Molecular Biology and Biophysics, Timakov Street 2, 630117 Novosibirsk, Russia
Ekaterina I. Yuzhik
Laboratory of Cytology and Cell Biology, Department of Molecular Mechanisms of Pathological Processes, Federal Research Center of Fundamental and Translational Medicine, Institute of Molecular Pathology and Pathomorphology, Timakov Street 2, 630117 Novosibirsk, Russia
Elena V. Koldysheva
Laboratory of Cytology and Cell Biology, Department of Molecular Mechanisms of Pathological Processes, Federal Research Center of Fundamental and Translational Medicine, Institute of Molecular Pathology and Pathomorphology, Timakov Street 2, 630117 Novosibirsk, Russia
Erik C. Korolenko
Department of Quantitative Studies, West Pender Campus, University Canada West, 626 West Pender Street, Vancouver, BC V6B 1V9, Canada
Evgeny L. Zavjalov
Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Academician Lavrentiev Avenue 10, 630090 Novosibirsk, Russia
Tamara G. Amstislavskaya
Scientific-Research Institute of Neurosciences and Medicine, Timakov Street 4, 630117 Novosibirsk, Russia
Db/db mice (carrying a mutation in the gene encoding leptin receptor) show autophagy suppression. Our aim was to evaluate the effect of autophagy inducer trehalose on liver and heart autophagy in db/db mice and to study inflammation dysregulation and the suitability of chitinases’ expression levels as diabetes markers. Thirty-eight male db/db mice and C57/BL mice (control) were used. The db/db model manifested inflammation symptoms: overexpression of TNF-α in the spleen and underexpression of IL-10 in the liver and spleen (cytokine imbalance). Simultaneously, we revealed decreased expression of chitotriosidase (CHIT1) and acid mammalian chitinase (CHIA) in the liver of db/db mice. CHIA expression in db/db mice is significantly lower only in the spleen. Trehalose treatment significantly reduced blood glucose concentration and glycated hemoglobin. Treatment of db/db mice by trehalose was followed by increased autophagy induction in the heart and liver (increased autolysosomes volume density studied by morphometric electron-microscopic method). Trehalose exerted beneficial cardiac effects possibly via increased lipophagy (uptake of lipid droplets). The autophagy activation by trehalose had several positive effects on the heart and liver of db/db mice; therefore, lipophagy activation seems to be a promising therapy for diabetes.