(OR20-04-23) Sulforaphane Ameliorates Cadmium-induced Hepatic Lipid Metabolism Disorder in Mice

Objectives: Sulforaphane (SFN) is an isothiocyanate found as glucoraphanin in cruciferous vegetables such as cabbage, cauliflower, and kale, and in higher concentrations in broccoli sprouts. Cadmium (Cd) is a commonly heavy metal pollutant, leading to hepatic injury and metabolic disorders. The liver is the major contributor to lipogenesis, accounting for nearly all de novo fatty acid synthesis (approximately 95 percent). PPARα and PPARγ are members of the peroxisome proliferator-activated receptors (PPARs) family that regulate various physiological processes, especially lipid and energy metabolism. Moreover, when lipid degeneration exists in the liver, both structural and functional mitochondrial problems occur, including reduced mitochondrial β-oxidation of free fatty acids. We hypothesized that SFN can improve disorders of lipid metabolism in chicken liver through PPARα/γ pathway. The mechanism of regulating lipid metabolism may be related to the improvement of mitochondrial function. To investigate the antagonism role of SFN on Cd-induced disorders in hepatic lipid metabolism, we used a chicken model fed with SFN.

Methods: 120 chicks were divided into four groups: control group, SFN group (50 mg SFN per kg of diet), Cd group (140mg CdCl₂ per kg of diet), and SFN + Cd group (50 mg SFN per kg and 140mg CdCl₂ per kg of diet) for 90 days.

Results: The results indicated that SFN attenuated Cd-induced hepatic pathological injury. SFN could activate the PGC1α/SIRT1/AMPK pathway and modulated the levels of PPARα/γ and SREBP1, which in turn attenuated Cd-induced alterations of very low-density lipoprotein (VLDL) synthesis, cholesterol metabolism synthesis, lipid oxidation synthesis, fatty acid synthesis and transport related molecules. Moreover, Cd exposure leads to decreased mitochondrial fusion, increased mitochondrial fission and impaired mitochondrial respiratory chain. Surprisingly, SFN treatment improved these negative effects.

Conclusions: Collectively, these findings indicated that SFN could alleviate Cd-induced lipid metabolism disorder via regulating the PPARα/γ signaling pathway and improving mitochondrial function.

Funding Sources: This study has received assistance from National Natural Science Foundation of China (No. 32172932).<br>*Corresponding author: Prof. Jin-Long Li. E-mail address: Jinlongli@neau.edu.cn