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 Article has an altmetric score of 3

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 2

HFD accelerates disease progression and affects survival of SIV-infected NHPs.

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HFD accelerates disease progression and affects survival of SIV-infected...
Peripheral CD4+ T cell depletion in SIV-infected AGMs (A) and PTMs (E) are shown as index of baseline levels and compared at key time points of SIV infection within HFD group with the Friedman test corrected for multiple comparisons and between HFD and control groups with Kruskal-Wallis test. Plasma viral loads (B), PBMC-associated viral DNA (C), and intestinal cell-associated DNA (D) levels in SIV-infected AGMs, and in SIV-infected PTMs (F–H) were compared at acute and chronic infection 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. BL, baseline (preinfection pre-HFD); Ac, acute infection; Chr, chronic infection; Fat, preinfection post-HFD; Nx, necropsy. Kaplan–Meier survival curves of SIV-infected PTMs (I) and AGMs (J) and PTMs are illustrated. Comparison between survival curves of HFD and control groups is performed with Mantel-Cox method. P values are presented on graphs.