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

Chuanyou Yi; Dandan Li; Xiao Guo; Jinhui Wang; Cenxi Liu; Guangxing Lu; Yan Sun; He Huang; Shangyu Hong; Jin Li

doi:10.3390/nu14112222

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.

Authors

Chuanyou Yi¹, Dandan Li¹, Xiao Guo¹, Jinhui Wang¹, Cenxi Liu¹, Guangxing Lu¹, Yan Sun², He Huang¹, Shangyu Hong¹, Jin Li¹

Affiliations

¹ State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, and Institute of Metabolism and Integrative Biology, Fudan University, Shanghai 200438, China.
² Masonic Medical Research Institute, 2150 Bleecker St., Utica, NY 13501, USA.

Abstract

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 (HFD^fri) gained less weight than those fed HFDs stored in the freezer (HFD^fre). Further analysis revealed that changes in the relative abundance of medium-chain triglyceride (MCT) in the HFD^fri, 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 HFD^fri. 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

Substances

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).