Lcorl, short for ligand-dependent corepressor-like, is a gene strongly associated with metabolic traits and body size regulation in humans and livestock [1,2,3,4,5,6,7,8]. Genome-wide association studies (GWAS) have linked it to glucose homeostasis, body weight, and other metabolic parameters. It may be involved in growth-related pathways, as its expression is associated with the regulation of genes downstream of GH signaling, as well as those related to glucose and lipid metabolism [1].

Functional investigations using Lcorl knockout mice (Lcorl-/-) have provided insights into its role. Lcorl-/-pups are born smaller but reach normal weight later. As they age, these mice remain lean with decreased daily food intake. Their glucose tolerance and insulin sensitivity are improved, likely due to reduced circulating levels of IGF-1 and altered gene expression in the liver [1].

In conclusion, Lcorl plays a crucial role in regulating growth and metabolism. The use of Lcorl knockout mouse models has revealed its significance in maintaining normal body size, glucose homeostasis, and lipid metabolism. These findings are congruent with GWAS-identified associations in humans and livestock, highlighting Lcorl's importance in understanding metabolic diseases and growth-related traits [1].

References:

1. Wyler, Steven C, Gahlot, Surbhi, Bideyan, Lara, Fujikawa, Teppei, Elmquist, Joel K. . LCoRL Regulates Growth and Metabolism. In Endocrinology, 165, . doi:10.1210/endocr/bqae146. https://pubmed.ncbi.nlm.nih.gov/39467326/

2. Takasuga, Akiko. 2015. PLAG1 and NCAPG-LCORL in livestock. In Animal science journal = Nihon chikusan Gakkaiho, 87, 159-67. doi:10.1111/asj.12417. https://pubmed.ncbi.nlm.nih.gov/26260584/

3. Saif, Rashid, Henkel, Jan, Jagannathan, Vidhya, Flury, Christine, Leeb, Tosso. 2020. The LCORL Locus is under Selection in Large-Sized Pakistani Goat Breeds. In Genes, 11, . doi:10.3390/genes11020168. https://pubmed.ncbi.nlm.nih.gov/32033434/

4. Yang, Yunzhou, Wang, Cui, Li, Guangquan, Wang, Huiying, He, Daqian. 2023. Significant association of mutations close to LCORL gene with growth performance in Zhedong white geese (Anser cygnoides). In Animal genetics, 54, 628-631. doi:10.1111/age.13342. https://pubmed.ncbi.nlm.nih.gov/37381668/

5. Bai, Fengting, Cai, Yudong, Qi, Min, Lenstra, Johannes A, Jiang, Yu. 2025. LCORL and STC2 Variants Increase Body Size and Growth Rate in Cattle and Other Animals. In Genomics, proteomics & bioinformatics, , . doi:10.1093/gpbjnl/qzaf025. https://pubmed.ncbi.nlm.nih.gov/40094447/

6. Wang, Tianqi, Shi, Xiaoyuan, Liu, Ziwen, Wang, Changfa, Chai, Wenqiong. 2022. A Novel A > G Polymorphism in the Intron 1 of LCORL Gene Is Significantly Associated with Hide Weight and Body Size in Dezhou Donkey. In Animals : an open access journal from MDPI, 12, . doi:10.3390/ani12192581. https://pubmed.ncbi.nlm.nih.gov/36230323/

7. Majeres, Leif E, Dilger, Anna C, Shike, Daniel W, McCann, Joshua C, Beever, Jonathan E. 2024. Defining a Haplotype Encompassing the LCORL-NCAPG Locus Associated with Increased Lean Growth in Beef Cattle. In Genes, 15, . doi:10.3390/genes15050576. https://pubmed.ncbi.nlm.nih.gov/38790206/

8. Metzger, Julia, Schrimpf, Rahel, Philipp, Ute, Distl, Ottmar. 2013. Expression levels of LCORL are associated with body size in horses. In PloS one, 8, e56497. doi:10.1371/journal.pone.0056497. https://pubmed.ncbi.nlm.nih.gov/23418579/