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Long-term Dietary Macronutrients and Hepatic Gene Expression in Aging Mice.


ABSTRACT: Nutrition influences both hepatic function and aging, but mechanisms are poorly understood. Here, the effects of lifelong, ad libitum-fed diets varying in macronutrients and energy on hepatic gene expression were studied. Gene expression was measured using Affymetrix mouse arrays in livers of 46 mice aged 15 months fed one of 25 diets varying in protein, carbohydrates, fat, and energy density from 3 weeks of age. Gene expression was almost entirely influenced by protein intake. Carbohydrate and fat intake had few effects on gene expression compared with protein. Pathways and processes associated with protein intake included those involved with mitochondrial function, metabolic signaling (PI3K-Akt, AMPK, mTOR) and metabolism of protein and amino acids. Protein intake had variable effects on genes associated with regulation of longevity and influenced by caloric restriction. Among the genes of interest with expression that were significantly associated with protein intake are Cth, Gls2, Igf1, and Nnmt, which were increased with higher protein intake, and Igf2bp2, Fgf21, Prkab2, and Mtor, which were increased with lower protein intake. Dietary protein has a powerful impact on hepatic gene expression in older mice, with some overlap with genes previously reported to be involved with regulation of longevity or caloric restriction.

SUBMITTER: Gokarn R 

PROVIDER: S-EPMC6454416 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Long-term Dietary Macronutrients and Hepatic Gene Expression in Aging Mice.

Gokarn Rahul R   Solon-Biet Samantha M SM   Cogger Victoria C VC   Cooney Gregory J GJ   Wahl Devin D   McMahon Aisling C AC   Mitchell James R JR   Mitchell Sarah J SJ   Hine Christopher C   de Cabo Rafael R   Raubenheimer David D   Simpson Stephen J SJ   Le Couteur David G DG  

The journals of gerontology. Series A, Biological sciences and medical sciences 20181101 12


Nutrition influences both hepatic function and aging, but mechanisms are poorly understood. Here, the effects of lifelong, ad libitum-fed diets varying in macronutrients and energy on hepatic gene expression were studied. Gene expression was measured using Affymetrix mouse arrays in livers of 46 mice aged 15 months fed one of 25 diets varying in protein, carbohydrates, fat, and energy density from 3 weeks of age. Gene expression was almost entirely influenced by protein intake. Carbohydrate and  ...[more]

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