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. 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. 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.

中文翻译：

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赖氨酸2-羟基异丁酰化水平测定猪脂肪组织中的脂肪生成和脂肪积累


背膘沉积过多会降低胴体等级，这是养猪业的一个主要问题，尤其是大多数肥胖型猪品种。猪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)，在癌细胞的转录、能量代谢和转移中发挥重要作用，但其在脂肪形成和脂肪积累中的作用尚未被证实。在这项研究中，我们首先分析了纤维脂肪祖细胞（FAP）、肌源性前体细胞（Myo）和间充质干细胞（MSC）的乙酰化（Kac）、Khib、巴豆酰化（Kcr）和琥珀酰化（Ksu）的修饰水平。并发现仅Khib修饰在FAPs中的分化潜力显着高于MSCs。一致地，与其调节酶赖氨酸乙酰转移酶 5 (KAT5) 和组蛋白脱乙酰酶 2 (HDAC2) 蛋白水平平行，Khib 水平在 FAP 的脂肪形成分化过程中呈二次方增加 (P < 0.01)。 FAP 中 KAT5 敲低抑制脂肪形成分化，而 HDAC2 敲低则增强脂肪形成分化。我们还通过比较分别来自肥胖型猪（莱芜猪）和瘦型猪（杜洛克猪）的 FAP 和背膘组织中的 Khib 水平，证明了 Khib 修饰有利于脂肪形成分化和脂肪积累。因此，KAT5 和 HDAC2 的表达模式与肥胖型和瘦型猪的背膘积累程度非常匹配。 我们从蛋白质翻译修饰的角度，首次揭示了Khib在​​猪脂肪生成和脂肪沉积中的作用，为通过遗传选择和营养策略改善肥胖型猪的脂肪积累和分布提供了新的线索。猪。