Hr, known as Hairless, is a transcriptional corepressor mainly expressed in the skin. It plays a crucial role in regulating hair follicle (HF) morphogenesis and hair cycling, and is associated with the Wnt/β-catenin signaling pathway which is vital for skin and HF homeostasis [2].

In a study on male wild-type (Hr+/+) and Hr null (Hr-/-) mice, Hr deficiency was found to mitigate high-fat diet (HFD)-induced obesity and insulin resistance. This was due to increased energy expenditure in Hr-/-mice, along with elevated levels of thermogenic protein uncoupling protein 1 (Ucp1) and its key transcriptional regulators (PPARγ and PGC1α) in their brown adipose tissue (BAT) [1]. In the Hairpoor (Hr(Hp)) mouse model, an Hr mutant, increased expression of Dkk1 (a Wnt inhibitor) by HR was related to abnormal HF development and hair cycle alteration [2].

In conclusion, Hr is essential for hair-related biological processes and metabolism. Gene knockout mouse models, such as Hr null and Hr(Hp) mice, have revealed its role in protecting against HFD-induced obesity and insulin resistance, as well as its impact on hair cycle regulation. These findings contribute to understanding related disease mechanisms and potentially developing therapeutic strategies for obesity-related metabolic disorders and hair disorders.

References:

1. Wang, Hongwei, Guo, Haoyu, Zhu, Kuicheng, He, Long, Yang, Jian-Jun. 2024. Hairless (Hr) Deficiency Mitigates High-Fat Diet-Induced Obesity and Insulin Resistance in Mice. In Advanced biology, 8, e2300635. doi:10.1002/adbi.202300635. https://pubmed.ncbi.nlm.nih.gov/38655702/

2. Kim, Bong-Kyu, Lee, Hwa-Young, Kim, Injung, Park, Jongkeun, Yoon, Sungjoo K. 2014. Increased expression of Dkk1 by HR is associated with alteration of hair cycle in hairpoor mice. In Journal of dermatological science, 74, 81-7. doi:10.1016/j.jdermsci.2013.12.007. https://pubmed.ncbi.nlm.nih.gov/24447645/