赖氨酸 2-羟基异丁酰化水平决定了猪脂肪组织中的脂肪生成和脂肪积累。

IF 6.3 Q1 AGRICULTURE, DAIRY & ANIMAL SCIENCE Journal of Animal Science and Biotechnology Pub Date : 2024-07-12 DOI:10.1186/s40104-024-01058-9
Enfa Yan, Mingyang Tan, Ning Jiao, Linjuan He, Boyang Wan, Xin Zhang, Jingdong Yin
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引用次数: 0

摘要

背景:背膘沉积过多会降低胴体等级,这是养猪业关注的一个主要问题,尤其是在大多数肥胖型猪种中。猪的脂肪生成和脂肪积累的机制仍不清楚。赖氨酸 2- 羟基异丁酰化(Khib)是一种新型蛋白质翻译后修饰(PTM),在转录、能量代谢和癌细胞转移中发挥重要作用,但其在脂肪生成和脂肪堆积中的作用尚未得到证实:本研究首先分析了具有不同分化潜能的纤维-脂肪生成原(FAPs)、肌生成前体(Myo)和间充质干细胞(MSCs)的乙酰化(Kac)、Khib、巴豆酰化(Kcr)和琥珀酰化(Ksu)的修饰水平。与之一致的是,在其调控酶赖氨酸乙酰转移酶5(KAT5)和组蛋白去乙酰化酶2(HDAC2)蛋白水平升高的同时,Khib水平也呈四倍增长(P结论):从蛋白质转译修饰的角度,我们首次揭示了 Khib 在猪脂肪生成和脂肪沉积中的作用,为肥胖型猪通过遗传选择和营养策略改善脂肪积累和分布提供了新的线索。
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Lysine 2-hydroxyisobutyrylation levels determined adipogenesis and fat accumulation in adipose tissue in pigs.

Background: Excessive backfat deposition lowering carcass grade is a major concern in the pig industry, especially in most breeds of obese type pigs. The mechanisms involved in adipogenesis and fat accumulation in pigs remain unclear. Lysine 2-hydroxyisobutyrylation (Khib), is a novel protein post-translational modification (PTM), which play an important role in transcription, energy metabolism and metastasis of cancer cells, but its role in adipogenesis and fat accumulation has not been shown.

Results: In this study, we first analyzed the modification levels of acetylation (Kac), Khib, crotonylation (Kcr) and succinylation (Ksu) of fibro-adipogenic progenitors (FAPs), myogenic precursors (Myo) and mesenchymal stem cells (MSCs) with varied differentiation potential, and found that only Khib modification in FAPs was significantly higher than that in MSCs. Consistently, in parallel with its regulatory enzymes lysine acetyltransferase 5 (KAT5) and histone deacetylase 2 (HDAC2) protein levels, the Khib levels increased quadratically (P < 0.01) during adipogenic differentiation of FAPs. KAT5 knockdown in FAPs inhibited adipogenic differentiation, while HDAC2 knockdown enhanced adipogenic differentiation. We also demonstrated that Khib modification favored to adipogenic differentiation and fat accumulation by comparing Khib levels in FAPs and backfat tissues both derived from obese-type pigs (Laiwu pigs) and lean-type pigs (Duroc pigs), respectively. Accordingly, the expression patterns of KAT5 and HDAC2 matched well to the degree of backfat accumulation in obese- and lean-type pigs.

Conclusions: From the perspective of protein translational modification, we are the first to reveal the role of Khib in adipogenesis and fat deposition in pigs, and provided new clues for the improvement of fat accumulation and distribution as expected via genetic selection and nutritional strategy in obese-type pigs.

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