Senthil Kumar Jeevotham, Mehboob Muhammad Zubair, Lei Xia
Department of Biochemistry and Molecular Biology, Oklahoma State University, Stillwater, Oklahoma, United States.
Am J Physiol Endocrinol Metab. 2025 Feb 1;328(2):E139-E147. doi: 10.1152/ajpendo.00353.2024. Epub 2024 Dec 19.
The rising prevalence of metabolic diseases is a significant global health concern. Beyond lifestyle management, targeting key molecules involved in metabolic regulation is essential. C1q/TNF-related protein 6 (CTRP6) is notably associated with glucose and lipid metabolism, with numerous studies highlighting its regulatory functions in metabolic diseases. This review summarizes the current knowledge on CTRP6, focusing on its gene expression profiles, protein structure, gene regulation, and role in metabolic diseases. CTRP6 is widely expressed across various tissues and features four distinct domains, with the C1q domain predicted to bind to its receptor. Notably, serum levels of CTRP6 are significantly elevated in patients with obesity and type 2 diabetes. In these conditions, adipose tissue serves as a key source of CTRP6 and its involvement in adipose tissue expansion, inflammation, and nutrient sensing has been observed in several studies. CTRP6 is also implicated in type 1 diabetes, gestational diabetes mellitus, and diabetic complications, particularly diabetic nephropathy. Although some studies have suggested that CTRP6 has protective roles in atherosclerotic cell models, myocardial infarction rat models, and ischemia/reperfusion injury mouse models, methodological issues such as unreliable antibodies and unstrict controls make it difficult to draw accurate conclusions from these studies. Patients with polycystic ovary syndrome (PCOS) exhibit elevated serum levels of CTRP6, although its direct impact on PCOS phenotypes remains unclear. In conclusion, CTRP6 emerges as a promising therapeutic target for metabolic diseases. A deeper understanding of CTRP6 will empower the scientific community to develop effective interventions to address the increasing prevalence of these diseases.
代谢性疾病患病率的上升是一个重大的全球健康问题。除了生活方式管理外，针对参与代谢调节的关键分子至关重要。C1q/TNF相关蛋白6（CTRP6）与葡萄糖和脂质代谢显著相关，众多研究强调了其在代谢性疾病中的调节功能。本综述总结了关于CTRP6的现有知识，重点关注其基因表达谱、蛋白质结构、基因调控及其在代谢性疾病中的作用。CTRP6在各种组织中广泛表达，具有四个不同的结构域，预测C1q结构域可与其受体结合。值得注意的是，肥胖和2型糖尿病患者的血清CTRP6水平显著升高。在这些情况下，脂肪组织是CTRP6的关键来源，并且在多项研究中已观察到其参与脂肪组织扩张、炎症和营养感知。CTRP6还与1型糖尿病、妊娠期糖尿病和糖尿病并发症，特别是糖尿病肾病有关。尽管一些研究表明CTRP6在动脉粥样硬化细胞模型、心肌梗死大鼠模型和缺血/再灌注损伤小鼠模型中具有保护作用，但诸如抗体不可靠和对照不严格等方法学问题使得难以从这些研究中得出准确结论。多囊卵巢综合征（PCOS）患者的血清CTRP6水平升高，尽管其对PCOS表型的直接影响仍不清楚。总之，CTRP6成为代谢性疾病一个有前景的治疗靶点。对CTRP6的更深入了解将使科学界能够开发有效的干预措施，以应对这些疾病日益增加的患病率。
