The Storage Conditions of High-Fat Diet Are the Key Factors for Diet-Induced Obesity and Liver Damage

Nutrients. 2022 May 26;14(11):2222. doi: 10.3390/nu14112222.


The diet-induced obesity (DIO) mouse model has been widely used for obesity studies. The effects of storage conditions on the composition of nutrients in high-fat diets (HFDs) and their impact on metabolic homeostasis have not been systemically investigated. In the current study, we tested the effects of HFDs stored under different conditions and found that mice fed a HFD stored in the fridge (HFDfri) gained less weight than those fed HFDs stored in the freezer (HFDfre). Further analysis revealed that changes in the relative abundance of medium-chain triglyceride (MCT) in the HFDfri, which have much lower intestinal absorption rates, contributed to the body weight differences. In contrast, exacerbated liver damage and elevated levels of unfolded protein response (UPR) was observed in the mice fed by HFDfri. Depletion of the UPR-regulated gene Nnmt alleviated liver damage via the inhibition of the integrated stress response (ISR). Our study, for the first time, provides evidence that HFD storage conditions can have a significant impact on both body weight changes and liver damage in the DIO model.

Keywords: NNMT; high-fat diet; liver damage; medium-chain triglyceride; obesity; storage condition; unfolded protein response.

MeSH terms

  • Animals
  • Diet, High-Fat* / adverse effects
  • Liver* / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Obesity / metabolism
  • Triglycerides / metabolism


  • Triglycerides

Grants and funding

This research was funded MOST 2020YFA0803600, 2018YFA0801300, NSFC 32071138, and SKLGE-2118 (provided to J.L.), MOST 2021YFA0804801, NSFC 91957117 and 31971082, and IDH1322092/010 (provided to S.H.), and MOST 2019YFA0801900, 2020YF1402600, NSFC 92057115, and Shanghai Sailing Program 20YF1402600 (provided to H.H).