Sulforaphane Ameliorates Hepatic Lipid Metabolism via Modulating Lipophagy In Vivo and In Vitro

Although sulforaphane (SFN) is reported to ameliorate the excessive accumulation of lipid droplets (LDs) in hepatocytes, its underlying mechanism remains unclear. This paper aims to investigate how SFN induces hepatic LD degradation via activating macroautophagy. High-fat diet and free fatty acids (FFAs) were used to induce excessive LD formation in hepatocytes in vivo and in vitro, respectively. SFN-induced macroautophagy was shown by the increased LC3 protein expression both (1.32 ± 0.18) in vivo and (2.43 ± 0.22) in vitro. The mRNA levels of Lc3 (1.99 ± 0.16), Atg4 (2.12 ± 0.23), Ulk1 (1.19 ± 0.12), Atg7 (1.25 ± 0.11), and Atg5 (0.81 ± 0.1) genes were elevated by SFN. SFN individually enhanced the localization of LC3 (0.41 ± 0.15), LAMP1 (0.66 ± 0.14), ATG7 (0.26 ± 0.08), and ATG5 (0.38 ± 0.09) with LDs, indicating the occurrence of lipophagy. In the components of LDs isolated from SFN treatment, the expressions of LC3, ATG7, and ATG5 protein were largely increased both in vivo and in vitro. LDs were visualized in autophagosomes which confirmed that the lipophagy was triggered by SFN. Moreover, SFN treatment improved the profile of FFAs which was characterized by increasing the FFAs in liver (total FFA: 261.51 ± 39.58 μM/g) and serum (total FFA: 967.59 ± 239.18 nM/mL). After silencing the nrf2 gene, ATG7 and ATG5 protein expressions were decreased and attenuated this induction by SFN. Nrf2 gene silencing inversely increased TG contents. In summary, SFN enhanced the LD degradation via stimulating lipophagy in a Nrf2-dependent manner.