Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization of Education Ministry, Southwest Minzu University, Chengdu, China.
Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Exploitation of Sichuan Province, Southwest Minzu University, Chengdu, China.
BMC Genomics. 2024 Sep 11;25(1):850. doi: 10.1186/s12864-024-10755-8.
Adipose tissue affects not only the meat quality of domestic animals, but also human health. Adipocyte differentiation is regulated by a series of regulatory genes and cyclins. Four and half-LIM protein (FHL2) is positively correlated with the hypertrophy of adipocytes and can cause symptoms such as obesity and diabetes.
In the transcriptome sequencing analysis of intramuscular adipocytes after three days of differentiation, the differentially expressed gene FHL2 was found. To further explore the biological significance of the differentially expressed gene FHL2, which was downregulated in the mature adipocytes. We revealed the function of FHL2 in adipogenesis through the acquisition and loss of function of FHL2. The results showed that the overexpression of FHL2 significantly increased the expression of adipogenic genes (PPARγ, C/EBPβ) and the differentiation of intramuscular and subcutaneous adipocytes. However, silencing FHL2 significantly inhibited adipocyte differentiation. The overexpression of FHL2 increased the number of adipocytes stained with crystal violet and increased the mRNA expression of proliferation marker genes such as CCNE, PCNA, CCND and CDK2. In addition, it significantly increased the rate of EdU positive cells. In terms of apoptosis, overexpression of FHL2 significantly inhibited the expression of P53 and BAX in both intramuscular and subcutaneous adipocytes, which are involved in cell apoptosis. However, overexpression of FHL2 promoted the expression of BCL, but was rescued by the silencing of FHL2.
In summary, FHL2 may be a positive regulator of intramuscular and subcutaneous adipocyte differentiation and proliferation, and acts as a negative regulator of intramuscular and subcutaneous adipocyte apoptosis. These findings provide a theoretical basis for the subsequent elucidation of FHL2 in adipocytes.
脂肪组织不仅影响家畜的肉质,还影响人类健康。脂肪细胞分化受一系列调节基因和细胞周期蛋白的调节。四个半 LIM 蛋白(FHL2)与脂肪细胞肥大呈正相关,可引起肥胖和糖尿病等症状。
在分化 3 天后的肌内脂肪细胞转录组测序分析中,发现差异表达基因 FHL2。为了进一步探讨下调的成熟脂肪细胞中差异表达基因 FHL2 的生物学意义。我们通过获得和丧失 FHL2 的功能来揭示 FHL2 在脂肪生成中的作用。结果表明,FHL2 的过表达显著增加了脂肪生成基因(PPARγ、C/EBPβ)的表达和肌内和皮下脂肪细胞的分化。然而,沉默 FHL2 显著抑制了脂肪细胞分化。FHL2 的过表达显著增加了结晶紫染色的脂肪细胞数量,并增加了增殖标记基因如 CCNE、PCNA、CCND 和 CDK2 的 mRNA 表达。此外,它还显著增加了 EdU 阳性细胞的比例。在细胞凋亡方面,FHL2 的过表达显著抑制了肌内和皮下脂肪细胞中参与细胞凋亡的 P53 和 BAX 的表达。然而,FHL2 的过表达促进了 BCL 的表达,但被 FHL2 的沉默所挽救。
总之,FHL2 可能是肌内和皮下脂肪细胞分化和增殖的正向调节剂,也是肌内和皮下脂肪细胞凋亡的负向调节剂。这些发现为后续阐明 FHL2 在脂肪细胞中的作用提供了理论依据。