Apoptosis in the liver of male <em>db/db</em> mice during the development of obesity and type 2 diabetes

Obesity and diabetes mellitus are known to lead to the development of metabolic syndrome and non-alcoholic fatty liver disease (NAFLD). The mechanisms of programmed cell death are actively involved in maintaining cellular homeostasis along development of NAFLD. Proteins of the BCL-2 family are key r...

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Main Authors: S. V. Michurina, I. Yu. Ishchenko, S. A. Arkhipov, M. A. Cherepanova, D. V. Vasendin, E. L. Zavjalov
Format: Article
Language:English
Published: Siberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and Breeders 2020-07-01
Series:Вавиловский журнал генетики и селекции
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Online Access:https://vavilov.elpub.ru/jour/article/view/2510
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author S. V. Michurina
I. Yu. Ishchenko
S. A. Arkhipov
M. A. Cherepanova
D. V. Vasendin
E. L. Zavjalov
author_facet S. V. Michurina
I. Yu. Ishchenko
S. A. Arkhipov
M. A. Cherepanova
D. V. Vasendin
E. L. Zavjalov
author_sort S. V. Michurina
collection DOAJ
description Obesity and diabetes mellitus are known to lead to the development of metabolic syndrome and non-alcoholic fatty liver disease (NAFLD). The mechanisms of programmed cell death are actively involved in maintaining cellular homeostasis along development of NAFLD. Proteins of the BCL-2 family are key regulators of physiological and pathological apoptosis. Homozygous males of BKS.Cg-Dock7mLeprdb/+/+/J mice (db/db mice) are characterized by progressive obesity and the development of type 2 diabetes mellitus (DM2) with severe hyperglycemia at 4–8 weeks and organ lesions at 8–10 weeks of age. The aim of this research was to study the expression of molecular cell regulators of apoptosis in liver cells of db/db mice males at different stages of obesity and diabetes development (at the age of 10 and 18 weeks). Immunohistochemical analysis (using the indirect avidin-biotin peroxidase method) and morphometric evaluation of the expression of the antiapoptotic protein Bcl-2 and the proapoptotic protein Bad in liver cells of studied animals at different stages of obesity and DM2 were carried out. An excess of the value of the Bcl-2 protein staining area over the Bad protein staining area was revealed in the liver of 10-week-old animals. The Bcl-2/Bad expression area ratio in 10-week-old animals was twice as high as in 18-week-old animals, which indicates the presence of conditions for blocking apoptosis in the liver of younger db/db mice. At the 18th week of life, db/db mice displayed an almost threefold increase in the expression area of the Bad protein against the background of an unchanged expression of the Bcl-2 protein. The decrease in the Bcl-2/Bad staining area ratio in 18-week-old animals was due to the increase in the Bad expression area, which indicates the absence of antiapoptotic cell protection and creates conditions for activation of the mitochondrial pathway of apoptosis in the liver of male db/db mice with pronounced signs of obesity and DM2.
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spelling doaj-art-720cfe94a43743c99e8b3e3a37053c432025-02-01T09:58:08ZengSiberian Branch of the Russian Academy of Sciences, Federal Research Center Institute of Cytology and Genetics, The Vavilov Society of Geneticists and BreedersВавиловский журнал генетики и селекции2500-32592020-07-0124443544010.18699/VJ20.43-o1033Apoptosis in the liver of male <em>db/db</em> mice during the development of obesity and type 2 diabetesS. V. Michurina0I. Yu. Ishchenko1S. A. Arkhipov2M. A. Cherepanova3D. V. Vasendin4E. L. Zavjalov5Research Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of SciencesResearch Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of SciencesResearch Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of SciencesResearch Institute of Clinical and Experimental Lymphology – Branch of the Institute of Cytology and Genetics of Siberian Branch of the Russian Academy of SciencesSiberian State University of Geosystems and TechnologiesInstitute of Cytology and Genetics of Siberian Branch of the Russian Academy of SciencesObesity and diabetes mellitus are known to lead to the development of metabolic syndrome and non-alcoholic fatty liver disease (NAFLD). The mechanisms of programmed cell death are actively involved in maintaining cellular homeostasis along development of NAFLD. Proteins of the BCL-2 family are key regulators of physiological and pathological apoptosis. Homozygous males of BKS.Cg-Dock7mLeprdb/+/+/J mice (db/db mice) are characterized by progressive obesity and the development of type 2 diabetes mellitus (DM2) with severe hyperglycemia at 4–8 weeks and organ lesions at 8–10 weeks of age. The aim of this research was to study the expression of molecular cell regulators of apoptosis in liver cells of db/db mice males at different stages of obesity and diabetes development (at the age of 10 and 18 weeks). Immunohistochemical analysis (using the indirect avidin-biotin peroxidase method) and morphometric evaluation of the expression of the antiapoptotic protein Bcl-2 and the proapoptotic protein Bad in liver cells of studied animals at different stages of obesity and DM2 were carried out. An excess of the value of the Bcl-2 protein staining area over the Bad protein staining area was revealed in the liver of 10-week-old animals. The Bcl-2/Bad expression area ratio in 10-week-old animals was twice as high as in 18-week-old animals, which indicates the presence of conditions for blocking apoptosis in the liver of younger db/db mice. At the 18th week of life, db/db mice displayed an almost threefold increase in the expression area of the Bad protein against the background of an unchanged expression of the Bcl-2 protein. The decrease in the Bcl-2/Bad staining area ratio in 18-week-old animals was due to the increase in the Bad expression area, which indicates the absence of antiapoptotic cell protection and creates conditions for activation of the mitochondrial pathway of apoptosis in the liver of male db/db mice with pronounced signs of obesity and DM2.https://vavilov.elpub.ru/jour/article/view/2510db/db miceobesitytype 2 diabetes mellitus (dm2)liverendothelial cellshepatocytesbcl-2bad
spellingShingle S. V. Michurina
I. Yu. Ishchenko
S. A. Arkhipov
M. A. Cherepanova
D. V. Vasendin
E. L. Zavjalov
Apoptosis in the liver of male <em>db/db</em> mice during the development of obesity and type 2 diabetes
Вавиловский журнал генетики и селекции
db/db mice
obesity
type 2 diabetes mellitus (dm2)
liver
endothelial cells
hepatocytes
bcl-2
bad
title Apoptosis in the liver of male <em>db/db</em> mice during the development of obesity and type 2 diabetes
title_full Apoptosis in the liver of male <em>db/db</em> mice during the development of obesity and type 2 diabetes
title_fullStr Apoptosis in the liver of male <em>db/db</em> mice during the development of obesity and type 2 diabetes
title_full_unstemmed Apoptosis in the liver of male <em>db/db</em> mice during the development of obesity and type 2 diabetes
title_short Apoptosis in the liver of male <em>db/db</em> mice during the development of obesity and type 2 diabetes
title_sort apoptosis in the liver of male em db db em mice during the development of obesity and type 2 diabetes
topic db/db mice
obesity
type 2 diabetes mellitus (dm2)
liver
endothelial cells
hepatocytes
bcl-2
bad
url https://vavilov.elpub.ru/jour/article/view/2510
work_keys_str_mv AT svmichurina apoptosisintheliverofmaleemdbdbemmiceduringthedevelopmentofobesityandtype2diabetes
AT iyuishchenko apoptosisintheliverofmaleemdbdbemmiceduringthedevelopmentofobesityandtype2diabetes
AT saarkhipov apoptosisintheliverofmaleemdbdbemmiceduringthedevelopmentofobesityandtype2diabetes
AT macherepanova apoptosisintheliverofmaleemdbdbemmiceduringthedevelopmentofobesityandtype2diabetes
AT dvvasendin apoptosisintheliverofmaleemdbdbemmiceduringthedevelopmentofobesityandtype2diabetes
AT elzavjalov apoptosisintheliverofmaleemdbdbemmiceduringthedevelopmentofobesityandtype2diabetes