Previous research demonstrated that tomato powder presented impressed anti-nonalcoholic fatty liver disease (NAFLD) efficacy through restoring NAMPT/Sirt1 activity. Lycopene, the principal monomer component of tomato powder, also effectively attenuated NAFLD pathological features. However, whether lycopene exerted its beneficial effects via tunning NAMPT/Sirt1 activity is still unknown. To solve this problem, mouse primary hepatocytes were isolated and challenged with palmitate to induce the in vitro model of NAFLD. The cytotoxicity of palmitate and lycopene was tested by MTT assay. Then the “first hit” (i.e., hepatosteatosis) and the “second hit” (i.e., inflammation) parameters were examined following lycopene treatment. Mechanisms involved NAMPT/Sirt1-regulated lipogenesis were determined by western blotting and qRT-PCR. Our results found that lycopene had a high safety profile (no cytotoxicity at 100 μM), while palmitate exhibited potent cytotoxicity (significant cytotoxicity at 0.0625 mM). Finally, we choose 0.5 mM of palmitate and 20, 40 μM of lycopene as the model and intervention conditions, respectively. Under the model condition, lycopene effectively rescued the decrease in cell viability, ameliorate the lipid accumulation, and mitigated the inflammatory response. Further exploration found that activation of NAMPT/Sirt1 and blockage of downstream lipogenesis mediated its favorable effects. In summary, lycopene is sufficient to undo palmitate-induced “two-hit” in primary hepatocytes and is a prospective candidate for NAFLD therapy.

Yaoxiang Zhu, Yafang Chen, Lei Zhu, Xian Zheng, Xiaoying Zhou. Lycopene counteracts palmitate-induced “two-hit” in mouse primary hepatocytes via triggering NAMPT/Sirt1 pathway. Frontiers in Medical Science Research (2022) Vol. 4, Issue 8: 32-38. https://doi.org/10.25236/FMSR.2022.040807.

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