Effects of dietary macronutrients on the hepatic transcriptome and serum metabolome in mice

Yingga Wu, Cara Leanne Green, Guanlin Wang, Dengbao Yang, Li Li, Baoguo Li, Lu Wang, Min Li, Jianbo Li, Yanchao Xu, Xueying Zhang, Chaoqun Niu, Sumei Hu, Jacques Togo, Mohsen Mazidi, Davina Derous, Alex Douglas, John Speakman* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)
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Dietary macronutrient composition influences both hepatic function and aging. Previous work suggested that longevity and hepatic gene expression levels were highly responsive to dietary protein, but almost unaffected by other macronutrients. In contrast, we found expression of 4005, 4232, and 4292 genes in the livers of mice were significantly associated with changes in dietary protein (5%–30%), fat (20%–60%), and carbohydrate (10%–75%), respectively. More genes in aging-related pathways (notably mTOR, IGF-1, and NF-kappaB) had significant correlations with dietary fat intake than protein and carbohydrate intake, and the pattern of gene expression changes in relation to dietary fat intake was in the opposite direction to the effect of graded levels of caloric restriction consistent with dietary fat having a negative impact on aging. We found 732, 808, and 995 serum metabolites were significantly correlated with dietary protein (5%–30%), fat (8.3%–80%), and carbohydrate (10%–80%) contents, respectively. Metabolomics pathway analysis revealed sphingosine-1-phosphate signaling was the significantly affected pathway by dietary fat content which has also been identified as significant changed metabolic pathway in the previous caloric restriction study. Our results suggest dietary fat has major impact on aging-related gene and metabolic pathways compared with other macronutrients.
Original languageEnglish
Article numbere13585
Number of pages18
JournalAging Cell
Issue number4
Early online date10 Mar 2022
Publication statusPublished - 14 Apr 2022

Bibliographical note

The study was funded by National Key R&D Program of China (2019YFA0801900), National Postdoctoral Program for Innovative Talents (BX2021357), Postdoctoral Science Foundation (2021M693393) the Chinese Academy of Sciences Strategic Program (XDB13030100), the National Natural Science Foundation of China (91649108), a PIFI professorial fellowship from CAS and a Wolfson merit award from the UK Royal Society (all to J.R.S unless stated).

Data Availability Statement

The data that support the findings of this study are available from the authors upon request. The metabolomics and transcriptomics data have been uploaded on Mendeley and relevant DOI is as follows: 10.17632/2s5ccsspfk.2. I confirm that I have included a citation for available data in my references section.


  • aging
  • transcriptome
  • carbohydrate
  • fat
  • metabolite
  • protein


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