Late-Onset Calorie Restriction Improves Lipid Metabolism and Aggravates Inflammation in the Liver of Old Wistar Rats

Aging is a progressive process that could disturb metabolic homeostasis in the liver via ectopic lipid accumulation, oxidative stress, and deterioration of inflammatory response. Although calorie restriction (CR) is recognized as beneficial for life span and health span prolongation, it is still unc...

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Main Authors: Ana Teofilović, Miloš Vratarić, Nataša Veličković, Danijela Vojnović Milutinović, Aleksandra Mladenovic, Milica Prvulovic, Ana Djordjevic
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-05-01
Series:Frontiers in Nutrition
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fnut.2022.899255/full
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author Ana Teofilović
Miloš Vratarić
Nataša Veličković
Danijela Vojnović Milutinović
Aleksandra Mladenovic
Milica Prvulovic
Ana Djordjevic
author_facet Ana Teofilović
Miloš Vratarić
Nataša Veličković
Danijela Vojnović Milutinović
Aleksandra Mladenovic
Milica Prvulovic
Ana Djordjevic
author_sort Ana Teofilović
collection DOAJ
description Aging is a progressive process that could disturb metabolic homeostasis in the liver via ectopic lipid accumulation, oxidative stress, and deterioration of inflammatory response. Although calorie restriction (CR) is recognized as beneficial for life span and health span prolongation, it is still unclear how late-onset CR, characterized by late beginning and short duration, affects age-related processes. The aim of this study was to examine how late-onset CR-induced metabolic adjustments impact lipid status and inflammation in the liver of old rats. The experiments were conducted on aging male Wistar rats fed ad libitum (AL) or exposed to late-onset CR (60% of AL daily intake) from 21st to 24th month. The results showed that late-onset CR reduces body weight, visceral adipose tissue and liver mass, and triglyceride levels when compared to old animals on AL diet. The ameliorating effects of CR on lipid metabolism include increased activity of AMP-activated protein kinase, suppressed de novo fatty acid synthesis, stimulated β-oxidation, decreased lipotoxicity, and limited triglyceride synthesis and packaging in the liver. Restricted diet regime, however, does not improve expression of antioxidant enzymes, although it leads to progression of age-related inflammation in the liver, partially through lower corticosterone concentration and decreased activation of glucocorticoid receptor. In conclusion, late-onset CR is able to restore age-related imbalance of lipid metabolism in the liver, but has a negative impact on hepatic inflammatory status, implying that the type of diet for older individuals must be balanced and chosen carefully with appropriate duration and start point.
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spelling doaj.art-4d34ecdf892a4f029ac8069ecfcd9b972022-12-22T00:29:56ZengFrontiers Media S.A.Frontiers in Nutrition2296-861X2022-05-01910.3389/fnut.2022.899255899255Late-Onset Calorie Restriction Improves Lipid Metabolism and Aggravates Inflammation in the Liver of Old Wistar RatsAna Teofilović0Miloš Vratarić1Nataša Veličković2Danijela Vojnović Milutinović3Aleksandra Mladenovic4Milica Prvulovic5Ana Djordjevic6Department of Biochemistry, Institute for Biological Research “Siniša Stanković” – National Institute of Republic of Serbia, University of Belgrade, Belgrade, SerbiaDepartment of Biochemistry, Institute for Biological Research “Siniša Stanković” – National Institute of Republic of Serbia, University of Belgrade, Belgrade, SerbiaDepartment of Biochemistry, Institute for Biological Research “Siniša Stanković” – National Institute of Republic of Serbia, University of Belgrade, Belgrade, SerbiaDepartment of Biochemistry, Institute for Biological Research “Siniša Stanković” – National Institute of Republic of Serbia, University of Belgrade, Belgrade, SerbiaDepartment of Neurobiology, Institute for Biological Research “Siniša Stanković” – National Institute of Republic of Serbia, University of Belgrade, Belgrade, SerbiaDepartment of Neurobiology, Institute for Biological Research “Siniša Stanković” – National Institute of Republic of Serbia, University of Belgrade, Belgrade, SerbiaDepartment of Biochemistry, Institute for Biological Research “Siniša Stanković” – National Institute of Republic of Serbia, University of Belgrade, Belgrade, SerbiaAging is a progressive process that could disturb metabolic homeostasis in the liver via ectopic lipid accumulation, oxidative stress, and deterioration of inflammatory response. Although calorie restriction (CR) is recognized as beneficial for life span and health span prolongation, it is still unclear how late-onset CR, characterized by late beginning and short duration, affects age-related processes. The aim of this study was to examine how late-onset CR-induced metabolic adjustments impact lipid status and inflammation in the liver of old rats. The experiments were conducted on aging male Wistar rats fed ad libitum (AL) or exposed to late-onset CR (60% of AL daily intake) from 21st to 24th month. The results showed that late-onset CR reduces body weight, visceral adipose tissue and liver mass, and triglyceride levels when compared to old animals on AL diet. The ameliorating effects of CR on lipid metabolism include increased activity of AMP-activated protein kinase, suppressed de novo fatty acid synthesis, stimulated β-oxidation, decreased lipotoxicity, and limited triglyceride synthesis and packaging in the liver. Restricted diet regime, however, does not improve expression of antioxidant enzymes, although it leads to progression of age-related inflammation in the liver, partially through lower corticosterone concentration and decreased activation of glucocorticoid receptor. In conclusion, late-onset CR is able to restore age-related imbalance of lipid metabolism in the liver, but has a negative impact on hepatic inflammatory status, implying that the type of diet for older individuals must be balanced and chosen carefully with appropriate duration and start point.https://www.frontiersin.org/articles/10.3389/fnut.2022.899255/fullcalorie restrictionlipid metabolisminflammationliveraging
spellingShingle Ana Teofilović
Miloš Vratarić
Nataša Veličković
Danijela Vojnović Milutinović
Aleksandra Mladenovic
Milica Prvulovic
Ana Djordjevic
Late-Onset Calorie Restriction Improves Lipid Metabolism and Aggravates Inflammation in the Liver of Old Wistar Rats
Frontiers in Nutrition
calorie restriction
lipid metabolism
inflammation
liver
aging
title Late-Onset Calorie Restriction Improves Lipid Metabolism and Aggravates Inflammation in the Liver of Old Wistar Rats
title_full Late-Onset Calorie Restriction Improves Lipid Metabolism and Aggravates Inflammation in the Liver of Old Wistar Rats
title_fullStr Late-Onset Calorie Restriction Improves Lipid Metabolism and Aggravates Inflammation in the Liver of Old Wistar Rats
title_full_unstemmed Late-Onset Calorie Restriction Improves Lipid Metabolism and Aggravates Inflammation in the Liver of Old Wistar Rats
title_short Late-Onset Calorie Restriction Improves Lipid Metabolism and Aggravates Inflammation in the Liver of Old Wistar Rats
title_sort late onset calorie restriction improves lipid metabolism and aggravates inflammation in the liver of old wistar rats
topic calorie restriction
lipid metabolism
inflammation
liver
aging
url https://www.frontiersin.org/articles/10.3389/fnut.2022.899255/full
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