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Ileal transcriptome analysis in obese rats induced by high-fat diets and an adenoviral infection

International Journal of Obesity volume 43, pages 2134–2142 (2019)Cite this article

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Abstract

Background

Obesity has become a worldwide epidemic affecting millions of people. Obesity and associated health consequences tend to be complicated by diverse causes and multi-systemic involvement. Previous studies have investigated obesity induced by a single factor, such as a high-fat diet (HF) of typical energy-dense food and infection by an adipogenic virus, such as a widely studied human adenovirus serotype 36 (Ad-36). In this study, we hypothesized and investigated the synergistic effect of two causal factors, HF and Ad-36, in obesity induction.

Methods

The 7-week-old Wistar rats (n = 1214/group) were randomly divided into weight-matched groups and induced for obesity with mock-control, HF, Ad-36, or HF + Ad-36 for 8–30 weeks, and compared for obesity phenotype. A global transcriptomic RNA-Seq analysis was used to profile signature gene response pathways in ileal tissues from 8-week control and obese animals during this early phase of obesity induction.

Results

HF only and particularly co-administration of Ad-36 and HF (HF + Ad-36) induced significant obesity in rats (p < 0.05 or p < 0.005). Compared with either Ad-36 or HF alone, HF + Ad-36 treatment significantly aggravates obesity in rats regarding body weight (n = 12–14/group) and adiposity index (n = 6–7). Genome-wide transcriptomic analyses of intestinal tissues revealed signature genes on an inter-systemic scale, including many genes in the pathways of circadian rhythm and antiviral immunity focusing on IFN signaling.

Conclusions

Ad-36 exacerbated the induction of obesity in rats compared with those treated with HF alone. Gene-responsive pathways involved in circadian rhythm and antiviral immunity in ileal tissues were significantly (p < 0.05, and FDR < 0.01) regulated during the early phase of obesity induction. This study provided a co-factorial model for obesity induction and profiled molecular targets for further validation and molecular manipulation.

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Acknowledgements

We thank Dr. Barbara Lutjemeier, Mr. Andrew Schade, Ms. Lyndie Holmes, and Ms. Jessica Pearson for their excellent technical support.

Funding

This work was primarily supported by NIH P20-RR017686 (KSU), and in part by the USDA NIFA AFRI 2013-67015-21236 and USDA NIFA AFRI 2015-665 67015-23216 to YS.

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Authors and Affiliations

  1. Department of Agricultural and Environmental Sciences, College of Agriculture, Tennessee State University, 3500 John A. Merritt Boulevard, Nashville, TN, USA

    Yongming Sang, Lauren E. Shields, Eric R. Sang, Haijun Si & Alexis Pigg

  2. Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA

    Frank Blecha

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  1. Yongming Sang
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  2. Lauren E. Shields
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Correspondence to Yongming Sang.

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Sang, Y., Shields, L.E., Sang, E.R. et al. Ileal transcriptome analysis in obese rats induced by high-fat diets and an adenoviral infection. Int J Obes 43, 2134–2142 (2019). https://doi.org/10.1038/s41366-019-0323-2

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