open access

Vol 59, No 3 (2021)
Original paper
Submitted: 2021-08-05
Accepted: 2021-08-24
Published online: 2021-09-13
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Short-term fenofibrate treatment improves ultrastructure of hepatocytes of old rats

Adrian Zubrzycki1, Agata Wronska1, Agata Zauszkiewicz-Pawlak1, Zbigniew Kmiec1
DOI: 10.5603/FHC.a2021.0018
·
Pubmed: 34515330
·
Folia Histochem Cytobiol 2021;59(3):167-177.
Affiliations
  1. Department of Histology, Medical University of Gdansk, Gdansk

open access

Vol 59, No 3 (2021)
ORIGINAL PAPERS
Submitted: 2021-08-05
Accepted: 2021-08-24
Published online: 2021-09-13

Abstract

Introduction. Fenofibrate (FN) is a hypolipemic drug used for the treatment of mixed dyslipidemia. Since in our previous study FN administration to young and old rats adversely affected the serum activity of liver marker enzymes, we decided to examine the effects of FN on liver ultrastructure of young and old animals.

Material and methods. Young and old rats were fed standard rodent chow supplemented with 0.1% FN for 30 days. Liver samples obtained from animals under full anesthesia were processed by routine methods to obtain ultrathin and histological sections for the examination by light microscopy (LM) and transmission electron microscopy (TEM). Furthermore, liver lysates were analyzed by Western blotting for the expression of the autophagy-related proteins LC3A/B and beclin 1.

Results. The ultrastructure of hepatocytes in both age groups was well-preserved, with the presence of abundant mitochondria, numerous peroxisomes and lysosomes, glycogen stored in the form of rosettes, and occasionally autolysosomes. However, hepatocytes of old control rats contained less mitochondria and peroxisomes, and more lipid droplets than cells of young animals. The effects of FN on liver ultrastructure were age-depended. FN increased the relative number of mitochondria and peroxisomes in the hepatocytes of old, and did not affect their number in young rats. Moreover, FN decreased and increased the relative number of lipid droplets in the hepatocytes of old and young rats, respectively. At the LM level, Oil Red O staining revealed smaller and larger lipid droplets within hepatocytes and non-parenchymal liver cells. In the livers of young and old rats lipid droplets were distributed mainly in the periportal zones of hepatic lobules. Morphometric analysis confirmed that livers of control old rats contained more lipid-stainable areas than those of young ones; however, no effect of FN was observed either in young or old rats. Despite larger size of autolysosomes and autophagic vacuoles in hepatocytes of old rats, the expression of autophagy-related proteins did not differ in the livers of control and fenofibrate-treated young and old animals.

Conclusions. The results of our study suggest that fenofibrate, apart from its hypolipemic action, may have beneficial effect on the energy metabolism in the liver of old individuals by increasing the number of mitochondria and peroxisomes in hepatocytes.

Abstract

Introduction. Fenofibrate (FN) is a hypolipemic drug used for the treatment of mixed dyslipidemia. Since in our previous study FN administration to young and old rats adversely affected the serum activity of liver marker enzymes, we decided to examine the effects of FN on liver ultrastructure of young and old animals.

Material and methods. Young and old rats were fed standard rodent chow supplemented with 0.1% FN for 30 days. Liver samples obtained from animals under full anesthesia were processed by routine methods to obtain ultrathin and histological sections for the examination by light microscopy (LM) and transmission electron microscopy (TEM). Furthermore, liver lysates were analyzed by Western blotting for the expression of the autophagy-related proteins LC3A/B and beclin 1.

Results. The ultrastructure of hepatocytes in both age groups was well-preserved, with the presence of abundant mitochondria, numerous peroxisomes and lysosomes, glycogen stored in the form of rosettes, and occasionally autolysosomes. However, hepatocytes of old control rats contained less mitochondria and peroxisomes, and more lipid droplets than cells of young animals. The effects of FN on liver ultrastructure were age-depended. FN increased the relative number of mitochondria and peroxisomes in the hepatocytes of old, and did not affect their number in young rats. Moreover, FN decreased and increased the relative number of lipid droplets in the hepatocytes of old and young rats, respectively. At the LM level, Oil Red O staining revealed smaller and larger lipid droplets within hepatocytes and non-parenchymal liver cells. In the livers of young and old rats lipid droplets were distributed mainly in the periportal zones of hepatic lobules. Morphometric analysis confirmed that livers of control old rats contained more lipid-stainable areas than those of young ones; however, no effect of FN was observed either in young or old rats. Despite larger size of autolysosomes and autophagic vacuoles in hepatocytes of old rats, the expression of autophagy-related proteins did not differ in the livers of control and fenofibrate-treated young and old animals.

Conclusions. The results of our study suggest that fenofibrate, apart from its hypolipemic action, may have beneficial effect on the energy metabolism in the liver of old individuals by increasing the number of mitochondria and peroxisomes in hepatocytes.

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Keywords

fenofibrate; aging; rat; liver; hepatocyte; lipid droplets; LC3A/B; beclin 1; TEM

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Title

Short-term fenofibrate treatment improves ultrastructure of hepatocytes of old rats

Journal

Folia Histochemica et Cytobiologica

Issue

Vol 59, No 3 (2021)

Article type

Original paper

Pages

167-177

Published online

2021-09-13

DOI

10.5603/FHC.a2021.0018

Pubmed

34515330

Bibliographic record

Folia Histochem Cytobiol 2021;59(3):167-177.

Keywords

fenofibrate
aging
rat
liver
hepatocyte
lipid droplets
LC3A/B
beclin 1
TEM

Authors

Adrian Zubrzycki
Agata Wronska
Agata Zauszkiewicz-Pawlak
Zbigniew Kmiec

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