Metap2-KO Mouse

Metap2, also known as methionine aminopeptidase 2, is an intracellular metalloprotease. It plays a critical role in regulating lipid metabolism, energy balance, and protein synthesis. It is involved in multiple biological processes and has emerged as a potential therapeutic target in various disease conditions. For instance, it is related to angiogenesis as it promotes the process, and its inhibitors can suppress angiogenesis [3,4].

Inhibiting Metap2 has shown promising effects in multiple disease models. In obese mice, Metap2 inhibitors decrease body weight and fat mass while increasing lean mass, acting directly on brown adipocytes to enhance β -adrenergic -signaling -stimulated activities and energy expenditure [1]. In sickle cell disease, Metap2 inhibition modifies hemoglobin S, delaying its polymerization, improving blood flow, and increasing oxygen affinity in Townes SCD mice [2]. In 3T3 -L1 pre -adipocytes, a Metap2 inhibitor blocks adipogenesis but increases glucose uptake [3]. In high -fat and -fructose -fed dogs, a Metap2 inhibitor improves glucose tolerance and net hepatic glucose uptake, suggesting potential for glycemic control in prediabetes and diabetes [5].

In conclusion, Metap2 is essential in regulating lipid and glucose metabolism, angiogenesis, and protein -related processes. Studies using various animal models, especially in obesity, diabetes, sickle cell disease, and adipocyte -related research, have revealed its significance in these disease areas. Understanding Metap2 through these model -based studies provides valuable insights for developing therapies targeting these diseases.

References:

1. Huang, Huey-Jing, Holub, Corine, Rolzin, Paul, Larson, Christopher J, Farrell, Pamela J. 2019. MetAP2 inhibition increases energy expenditure through direct action on brown adipocytes. In The Journal of biological chemistry, 294, 9567-9575. doi:10.1074/jbc.RA118.007302. https://pubmed.ncbi.nlm.nih.gov/31048375/

2. Demers, Melanie, Sturtevant, Sarah, Guertin, Kevin R, Higgins, John M, Light, David R. . MetAP2 inhibition modifies hemoglobin S to delay polymerization and improves blood flow in sickle cell disease. In Blood advances, 5, 1388-1402. doi:10.1182/bloodadvances.2020003670. https://pubmed.ncbi.nlm.nih.gov/33661300/

3. Siddik, Md Abu Bakkar, Das, Bhaskar C, Weiss, Louis, Dhurandhar, Nikhil V, Hegde, Vijay. . A MetAP2 inhibitor blocks adipogenesis, yet improves glucose uptake in cells. In Adipocyte, 8, 240-253. doi:10.1080/21623945.2019.1636627. https://pubmed.ncbi.nlm.nih.gov/31264515/

4. Datta, Bansidhar. 2009. Roles of P67/MetAP2 as a tumor suppressor. In Biochimica et biophysica acta, 1796, 281-92. doi:10.1016/j.bbcan.2009.08.002. https://pubmed.ncbi.nlm.nih.gov/19716858/

5. Moore, Mary Courtney, Coate, Katie C, Scott, Melanie, Farmer, Ben, Cherrington, Alan D. 2020. MetAP2 inhibitor treatment of high-fat and -fructose-fed dogs: impact on the response to oral glucose ingestion and a hyperinsulinemic hyperglycemic clamp. In American journal of physiology. Endocrinology and metabolism, 318, E514-E524. doi:10.1152/ajpendo.00451.2019. https://pubmed.ncbi.nlm.nih.gov/31990576/