High-fat diet exacerbates SIV pathogenesis and accelerates disease progression
Tianyu He, … , Cristian Apetrei, Ivona Pandrea
Tianyu He, … , Cristian Apetrei, Ivona Pandrea
Published November 11, 2019
Citation Information: J Clin Invest. 2019;129(12):5474-5488. https://doi.org/10.1172/JCI121208.
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Research Article AIDS/HIV

High-fat diet exacerbates SIV pathogenesis and accelerates disease progression

Abstract

Consuming a high-fat diet (HFD) is a risk factor for obesity and diabetes; both of these diseases are also associated with systemic inflammation, similar to HIV infection. A HFD induces intestinal dysbiosis and impairs liver function and coagulation, with a potential negative impact on HIV/SIV pathogenesis. We administered a HFD rich in saturated fats and cholesterol to nonpathogenic (African green monkeys) and pathogenic (pigtailed macaques) SIV hosts. The HFD had a negative impact on SIV disease progression in both species. Thus, increased cell-associated SIV DNA and RNA occurred in the HFD-receiving nonhuman primates, indicating a potential reservoir expansion. The HFD induced prominent immune cell infiltration in the adipose tissue, an important SIV reservoir, and heightened systemic immune activation and inflammation, altering the intestinal immune environment and triggering gut damage and microbial translocation. Furthermore, HFD altered lipid metabolism and HDL oxidation and also induced liver steatosis and fibrosis. These metabolic disturbances triggered incipient atherosclerosis and heightened cardiovascular risk in the SIV-infected HFD-receiving nonhuman primates. Our study demonstrates that dietary intake has a discernable impact on the natural history of HIV/SIV infections and suggests that dietary changes can be used as adjuvant approaches for HIV-infected subjects, to reduce inflammation and the risk of non-AIDS comorbidities and possibly other infectious diseases.

Authors

Tianyu He, Cuiling Xu, Noah Krampe, Stephanie M. Dillon, Paola Sette, Elizabeth Falwell, George S. Haret-Richter, Tiffany Butterfield, Tammy L. Dunsmore, William M. McFadden Jr., Kathryn J. Martin, Benjamin B. Policicchio, Kevin D. Raehtz, Ellen P. Penn, Russell P. Tracy, Ruy M. Ribeiro, Daniel N. Frank, Cara C. Wilson, Alan L. Landay, Cristian Apetrei, Ivona Pandrea

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Figure 7

HFD induces intestinal epithelial barrier damage and increases microbial translocation.

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HFD induces intestinal epithelial barrier damage and increases microbial...
(A) Representative images of jejunum stained for myeloperoxidase (brown) collected before infection, at 9 days after infection, and at necropsy from contemporary controls and HFD-receiving PTMs. Note substantially increased myeloperoxidase underneath the damaged epithelium and adjacent to the crypt abscess. Original magnifications: ×200. Quantification of the percent area of the jejunum positive for myeloperoxidase is shown in the right panel. Fold increase of LPS (B) and intestinal fatty-acid binding protein (C) to baseline levels in AGMs, as well as fold increase of intestinal fatty-acid binding protein (D) to baseline levels in PTMs are compared at key time points of SIV infection within HFD group with Friedman test corrected for multiple comparisons, and between HFD and control groups with Kruskal-Wallis test. Data are presented as individual values with medians. Sample size (n) and P values are presented on graphs. Ac, acute infection; BL, baseline (preinfection pre-HFD); Chr, chronic infection; Fat, preinfection post-HFD; Nx, necropsy.