High-fat diet exacerbates SIV pathogenesis and accelerates disease progression
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
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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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 6

HFD alters gut immune environment and activation states of the immune cells.

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HFD alters gut immune environment and activation states of the immune ce...
(A) Mucosal CD4+ T cell depletion in HFD-receiving and control AGMs is shown as an index of baseline levels and compared at key time points of SIV infection within the HFD group with Friedman test corrected for multiple comparisons, and between HFD and control groups with Kruskal-Wallis test. (B) Mucosal-naïve, central memory, and effector memory CD4+ T cells are shown as an index of total baseline mucosal CD4+ T cell levels and compared before and after HFD in preinfection AGMs with Friedman test. Frequencies of Glut-1, HLA-DR, and CD38 coexpressing CD4+ T cells (C), as well as CD80-expressing (D) and CD86-expressing (E) macrophages in the intestine of 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.