Alternate-Day High Fat-Normal Chow Diet Ameliorates HFD-Induced Obesity and Restores Intestinal Immunity

Abstract

Purpose

To investigate the effect of alternating-day diet regimens on high-fat diet-induced metabolic disorders in mice.

Materials and Methods

Eight-week-old C57BL/6J mice were fed with either a continuous normal chow diet (CD, n = 10), a continuous high-fat diet (HFD, n = 10), HFD alternating every 24 h with fasting (H-ADF, n = 20), or HFD alternating every 24 h with chow diet (H-ADC, n = 20) for 12 weeks. Weights were recorded weekly and oral glucose tolerance tests were performed 6 weeks after initiating the regimens. At the end of the study, blood samples were collected and serum insulin and lipids were measured; tissues were collected for histology and RNA-seq analysis.

Results

HFD significantly increased body weight and fat percentage, while HFD alternating with fasting or CD did not significantly affect body weight and fat percentage. The glucose intolerance induced by HFD was also significantly ameliorated in these two diet intervention groups. HFD-induced elevation of total cholesterol, low-density lipoprotein and insulin were also reduced in H-ADF and H-ADC groups. Moreover, HFD-disturbed immunity, presented by Lysozyme C-1 (Lyz1) immunostaining and RNA-seq, was restored in both alternating-regimen groups, especially, with H-ADC. At the transcriptional level, some cell proliferation and lipid absorption pathways were down-regulated in both H-ADF and H-ADC groups compared to the continuous HFD group.

Conclusion

Alternating an HFD with a normal diet every 24 h effectively controls weight and prevents metabolic disorders and may act by affecting both fat absorption and intestinal immunity.

Keywords:

• intermittent fasting
• high-fat diet
• intestines
• obesity
• absorption
• intestinal immunity

Acknowledgments

The authors thank Pamela B. Wright help with editing the English. We also thank Dr. Xiuqin Zhang for providing critical comments and scientific discussion, Ning Hou for their technical support, and Haibao Shang for animal experiments. This work was supported by the National Natural Science Foundation of China (81970690 and 81471063).

Author Contributions

All authors made a significant contribution to the work reported. D.Z.A. and Y.Y. conceived and designed the project, performed experiments, analyzed and interpreted data. W.Z. conceived the project. Y.X. and X.S. performed experiments. All authors took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no potential conflicts of interest relevant to this article.