Sfrp5, Secreted frizzled-related protein 5, is an anti-inflammatory adipocytokine secreted by adipocytes. It directly binds to Wnt, functioning as an antagonist in the Wnt signaling pathway. Sfrp5 is associated with energy homeostasis, insulin resistance, and has potential impacts on various biological processes and disease conditions such as atherosclerosis, obesity, and diabetes [1,5,6,7].

In obese children, the level of Sfrp5 is significantly lower compared to healthy children, while Wnt5a level is higher. Wnt5a can promote apoptosis of HUVEC cells through the Wnt5a/JNK/Caveolin-1 pathway, and Sfrp5 can inhibit this apoptosis by interfering with the pathway [2]. Central Sfrp5 signaling activates an InsR-Akt-PI3k-KATP channel pathway in the hypothalamus and brain-hepatic vagus neurocircuitry to decrease hepatic glucose production (HGP) and VLDL-TG secretion in HFD-fed rats [3]. Sfrp5 also inhibits melanin synthesis in melanocytes by suppressing the Wnt/β-catenin signaling, and its overexpression was found in vitiligo skin lesions [4].

In conclusion, Sfrp5 plays crucial roles in multiple biological processes including anti-inflammation, energy metabolism, and melanogenesis. Its deficiency or malfunction is associated with diseases like obesity, cardiovascular diseases, and vitiligo. Studies on Sfrp5, especially through in vivo models, help understand its functions in disease pathogenesis, potentially providing novel therapeutic targets for related disorders [2,3,4,6,7].

References:

1. Tong, Shan, Ji, Qingwei, Du, Yu, Zhu, Caizhong, Zhou, Yujie. 2019. Sfrp5/Wnt Pathway: A Protective Regulatory System in Atherosclerotic Cardiovascular Disease. In Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research, 39, 472-482. doi:10.1089/jir.2018.0154. https://pubmed.ncbi.nlm.nih.gov/31199714/

2. Liu, Weihua, Ji, Yuqiang, Chu, Haiping, Yang, Bin, Yin, Chunyan. . SFRP5 mediates downregulation of the wnt5a/caveolin-1/JNK signaling pathway. In The Journal of endocrinology, 247, 263-272. doi:10.1530/JOE-20-0328. https://pubmed.ncbi.nlm.nih.gov/33108333/

3. Li, Yang, Tian, Mingyuan, Yang, Mengliu, Zheng, Hongting, Li, Ling. 2019. Central Sfrp5 regulates hepatic glucose flux and VLDL-triglyceride secretion. In Metabolism: clinical and experimental, 103, 154029. doi:10.1016/j.metabol.2019.154029. https://pubmed.ncbi.nlm.nih.gov/31770545/

4. Zou, Dao-Pei, Chen, Yang-Mei, Zhang, Ling-Zhao, Gao, Tian-Wen, Chen, Jin. 2020. SFRP5 inhibits melanin synthesis of melanocytes in vitiligo by suppressing the Wnt/β-catenin signaling. In Genes & diseases, 8, 677-688. doi:10.1016/j.gendis.2020.06.003. https://pubmed.ncbi.nlm.nih.gov/34291139/

5. Jaikanth, Chandrasekaran, Gurumurthy, Prema, Indhumathi, Thillai, Cherian, Kotturathu M. 2014. Emergence of SFRP5 as a pleiotropic adipocytokine and its association with Wnt signaling pathways. In Minerva endocrinologica, 42, 280-289. doi:10.23736/S0391-1977.16.02232-X. https://pubmed.ncbi.nlm.nih.gov/25003224/

6. Koutaki, Diamanto, Michos, Athanasios, Bacopoulou, Flora, Charmandari, Evangelia. 2021. The Emerging Role of Sfrp5 and Wnt5a in the Pathogenesis of Obesity: Implications for a Healthy Diet and Lifestyle. In Nutrients, 13, . doi:10.3390/nu13072459. https://pubmed.ncbi.nlm.nih.gov/34371968/

7. Wang, Di, Zhang, Yaping, Shen, Chengxing. 2020. Research update on the association between SFRP5, an anti-inflammatory adipokine, with obesity, type 2 diabetes mellitus and coronary heart disease. In Journal of cellular and molecular medicine, 24, 2730-2735. doi:10.1111/jcmm.15023. https://pubmed.ncbi.nlm.nih.gov/32004418/