Lipid metabolism disorders are found ubiquitously in farmed fish and occur as a result of excessive fat accumulation. Previous studies have found that miR-33 is involved in lipid metabolism; however, its role in fish lipid metabolism is unclear. We sought to clarify this relationship in grass carp in vivo and in vitro. Our findings revealed the length of miR-33 to be 65 bp. Phylogenetic tree analysis showed that grass carp miR-33 was most closely related to fish miR-33 (Siganus canaliculatus). Hepatocytes transfected with miR-33 mimic displayed markedly raised TG content (P < 0.05) as well as increased levels of lipid synthesis-related transcription factors (P < 0.05). Compared with blank and saline groups, total serum cholesterol, AST, and LDL levels were suppressed in groups treated with the miR-33 antagomir (P < 0.05). Moreover, the expression levels of PPARγ and SREBP-1c mRNA were significantly decreased in contrast to those found in the control group (P < 0.05). Similar findings were noted in the expression of immune-related proinflammatory molecules (TNFα, IL-1β, IL-6, and NF-κB), which also demonstrated decreased levels (P < 0.05). Conversely, high expressions of anti-inflammatory factors (TGF-β1 and IL-10) were noted (P < 0.05). This investigation strongly supports the role of miR-33 in hepatopancreas-based lipid metabolism and immunity. miR-33 may have been highly conserved in early vertebrates in order to facilitate liver-specific metabolic and immunomodulatory functions. Our findings provide a basis for further investigations exploring the mechanisms surrounding fish lipid metabolism and may aid in preventing and treating immunocompromised fish as well as fish with fatty hepatopancreas, and other metabolic diseases.

脂肪代谢紊乱在养殖鱼类中普遍存在，并且是由于脂肪过多积累而发生的。之前的研究发现miR-33参与脂质代谢；然而，其在鱼类脂质代谢中的作用尚不清楚。我们试图在草鱼体内和体外阐明这种关系。我们的研究结果显示 miR-33 的长度为 65 bp。系统进化树分析表明，草鱼miR-33与鱼类miR-33（Siganus canaliculatus）的亲缘关系最为密切。转染miR-33模拟物的肝细胞显示TG含量显着升高（P  < 0.05）以及脂质合成相关转录因子水平升高（P < 0.05)。与空白组和生理盐水组相比，miR-33 antagomir 治疗组的血清总胆固醇、AST 和 LDL 水平受到抑制（P  < 0.05）。此外，与对照组相比，PPARγ和SREBP-1c mRNA的表达水平显着降低（P  < 0.05）。在免疫相关促炎分子（TNFα、IL-1β、IL-6 和 NF-κB）的表达中也发现了类似的发现，这也表明水平降低（P  < 0.05）。相反，注意到抗炎因子（TGF-β1 和 IL-10）的高表达（P < 0.05)。该研究强烈支持 miR-33 在基于肝胰腺的脂质代谢和免疫中的作用。miR-33 可能在早期脊椎动物中高度保守，以促进肝脏特异性代谢和免疫调节功能。我们的研究结果为进一步研究探索鱼类脂质代谢的机制提供了基础，并可能有助于预防和治疗免疫功能低下的鱼类以及患有脂肪肝的鱼类和其他代谢疾病。