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. 2020 Jul 29;7:361. doi: 10.3389/fmed.2020.00361

Figure 2.

Figure 2

The mechanistic scheme for indole alleviation of NAFLD. During NAFLD, hepatocytes release fat deposition-associated proinflammatory mediators and palmitate (hydrolysis product of very low-density lipoproteins), which act on macrophages to enhance the proinflammatory responses. Active macrophages release proinflammatory factors such as TNFα and IL-1β and act, via paracrine manners, to exacerbate the proinflammatory responses and fat accumulation in hepatocytes. Indole, a microbiota metabolite from tryptophan (Trp), acts to reduce hepatocyte fat deposition via suppressing the expression of FAS through a mechanism involving AhR activation. Moreover, indole reduces the inflammatory responses in both macrophages and hepatocytes and fat deposition in hepatocytes in a manner involving myeloid cell PFKFB3. Modified based on Krishnan, S., et al. Cell Reports, 2018. 23(4): p. 1099-1111 and Zheng et al. Front Med 2015; 9: 173-186.