Preadipocyte differentiation and lipid synthesis are critical steps for intramuscular fat (IMF) deposition and lipid metabolism homeostasis. IMF content of beef not only determines the ratio of muscle to adipose, but also determines the beef quality, flavor, and sensory characteristics. Maintaining lipid metabolism homeostasis is the key means of preventing and treating diabetes, obesity, and other metabolic diseases. SIRT6, which is an ADP-ribosyltransferase and NAD+-dependent deacetylase of acetyl and long-chain fatty acyl groups, playing central roles in lipid and glucose metabolism, is closely related to the occurrence of diabetes and obesity caused by overnutrition and aging. This study was based on bovine preadipocyte differentiation and an obese mice model, and comprehensively used transcriptome sequencing (RNA-seq) and morphological identification methods to explore the effects of inhibition of SIRT6 on differentiation and lipid synthesis, and related molecular mechanisms. Additionally, the feedback synergistic regulation of SIRT5 and SIRT6 on differentiation and lipid deposition was analyzed. The results showed that in the differentiation process of bovine preadipocytes, inhibition of SIRT5 significantly promoted SIRT6 expression. In addition, SIRT6 inhibited bovine preadipocyte differentiation and lipid synthesis, cooperating with SIRT5 to decrease lipid deposition, and repressed cell cycle arrest of preadipocytes. Moreover, in vivo verification experiments also obtained consistent results. Furthermore, SIRT6 inhibited preadipocyte differentiation and lipid deposition by activating the adenosine monophosphate activated protein kinase alpha (AMPKα) pathway. The above results provided a novel approach for understanding the functions of SIRT6 in regulating bovine adipocyte differentiation and lipid metabolism, as well as a new target for the treatment of diabetes and obesity in a clinical setting.

中文翻译：

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SIRT6与SIRT5协同通过AMPKα信号通路调节牛脂肪细胞的分化和脂质代谢。

脂肪细胞分化和脂质合成是肌肉内脂肪（IMF）沉积和脂质代谢稳态的关键步骤。牛肉的IMF含量不仅决定肌肉与脂肪的比例，而且决定牛肉的质量，风味和感官特性。维持脂质代谢的稳态是预防和治疗糖尿病，肥胖症和其他代谢性疾病的关键手段。SIRT6是乙酰基和长链脂肪酰基的ADP-核糖基转移酶和NAD +依赖性脱乙酰基酶，在脂质和葡萄糖代谢中起着重要作用，与营养过剩和衰老引起的糖尿病和肥胖症的发生密切相关。这项研究基于牛前脂肪细胞分化和肥胖小鼠模型，并广泛使用转录组测序（RNA-seq）和形态学鉴定方法，探讨SIRT6抑制作用对分化和脂质合成的影响，以及相关的分子机制。另外，分析了SIRT5和SIRT6对分化和脂质沉积的反馈协同调节。结果表明，在牛前脂肪细胞的分化过程中，抑制SIRT5可以显着促进SIRT6的表达。此外，SIRT6抑制牛前脂肪细胞的分化和脂质合成，与SIRT5协同作用以减少脂质沉积，并抑制前脂肪细胞的细胞周期停滞。此外，体内验证实验也获得了一致的结果。此外，SIRT6通过激活单磷酸腺苷激活的蛋白激酶α（AMPKα）途径来抑制前脂肪细胞的分化和脂质沉积。以上结果为理解SIRT6在调节牛脂肪细胞分化和脂质代谢中的功能提供了一种新颖的方法，并且为临床环境中糖尿病和肥胖症的治疗提供了新的靶点。