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

Abstract

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.

Preservation of Mitochondrial Membrane Potential is Necessary for Lifespan Extension from Dietary Restriction

“…The ability of DR to preserve Δψ m during early aging does not appear to involve the activity of UCPs, but instead requires both mitochondrial ANT and IF1 activity. We also find that fatty acid metabolism is required for preservation of Δψ m by DR, consistent with a recent report in worms that fatty acid metabolism promotes longevity [21], as well as numerous studies in mammals showing that DR increases fatty acid oxidation [36, 47-49]. While it remains difficult to quantify or control Δψ m in vivo in mammals, this work should serve to orient future experiments to define mechanisms underlying these observations in worms and other systems.…”

Short-Term Caloric Restriction and Subsequent Re-Feeding Compromise Liver Health and Associated Lipid Mediator Signaling in Aged Mice

“…As expected, short-term CR markedly reduced the body weight of the animals and, in line with previous studies, led to a plethora of changes to the hepatic microenvironment [ 20 , 46 , 47 , 48 ]. Overall, short-term CR failed to revert the release of inflammation-related cytokines and LM to levels found in young animals.…”

Sex‐specific effects of dietary restriction on physiological variables in Japanese quails

“…However, the changes were not significant in the second week in both sexes. Previous evidence from different species suggested that dietary restriction can reduce triglyceride levels (Mahoney et al, 2006;Teofilović et al, 2022;Zhan et al, 2007). Triglycerides are mainly derived from dietary sources, particularly from dietary fats and carbohydrates via the liver (Havel et al, 1962).…”