Kcp, also known as kielin/chordin-like protein, is a large secreted protein. It can enhance bone morphogenetic protein (BMP) signaling while suppressing TGF-β signaling, and is involved in the regulation of pathways related to lipid deposition and adipose tissue differentiation [1,2]. Kcp is of biological importance as it impacts physiological processes such as metabolism and is associated with diseases like non-alcoholic fatty liver disease (NAFLD) and obesity. Genetic models, especially mouse models, are valuable for studying Kcp's functions.

In gene knockout (KO) mouse models, aging Kcp-/-mice are more susceptible to developing hepatic steatosis and liver fibrosis, and when on a high-fat diet, young Kcp-/-mice are more prone to liver pathology compared to wild-type littermates [1]. On the other hand, mice expressing a Pepck-KCP transgene in the liver are resistant to high-fat diet-induced liver pathology. Also, Kcp-/-mice are more sensitive to obesity, glucose intolerance, adipose tissue inflammation and fibrosis, while transgenic mice overexpressing Kcp in the kidney, liver, and adipose tissues are resistant to high-fat diet-induced obesity with reduced white adipose tissue [2].

In conclusion, through model-based research, Kcp has been shown to play essential roles in regulating lipid metabolism in the liver and obesity-related metabolic processes. The KO mouse models have contributed significantly to understanding Kcp's role in NAFLD and obesity, providing insights into the underlying molecular mechanisms and potential therapeutic targets for these disease areas.

References:

1. Soofi, Abdul, Wolf, Katherine I, Ranghini, Egon J, Amin, Mohammad A, Dressler, Gregory R. 2016. The kielin/chordin-like protein KCP attenuates nonalcoholic fatty liver disease in mice. In American journal of physiology. Gastrointestinal and liver physiology, 311, G587-G598. doi:10.1152/ajpgi.00165.2016. https://pubmed.ncbi.nlm.nih.gov/27514479/

2. Soofi, Abdul, Wolf, Katherine I, Emont, Margo P, Ostwani, Wesam, Dressler, Gregory R. 2017. The kielin/chordin-like protein (KCP) attenuates high-fat diet-induced obesity and metabolic syndrome in mice. In The Journal of biological chemistry, 292, 9051-9062. doi:10.1074/jbc.M116.771428. https://pubmed.ncbi.nlm.nih.gov/28424263/