Adm2, also known as adrenomedullin 2 or intermedin (IMD), belongs to the CGRP superfamily and is a protective peptide. It binds to the receptor RAMP (1, 2, or 3):CLR complex, and is involved in multiple biological processes. It has been shown to impact adipose tissue function, embryo development, and immune responses, and is associated with diseases like non-alcoholic fatty liver disease (NAFLD), preeclampsia, and diabetic vascular calcification [1,2,3,5]. Genetic models, such as gene-knockout (KO) mouse models, can help to further clarify its specific functions in these processes.

In adipose-specific Adm2-overexpressing transgenic (aADM2-tg) mice fed a high-fat diet, decreased hepatic triglyceride accumulation was observed due to inhibited hepatic de novo lipogenesis. ADM2 decreased ceramide levels in adipocytes through upregulating ACER2, which catalyzes ceramide catabolism, and activation of adipocyte HIF2α was required for this process, suggesting its role in NAFLD [1]. In oocyte-specific Adm2-disrupted mice, ovarian follicle growth was enhanced after superovulation, but the developmental capacity of fertilized eggs was impaired, indicating that oocyte-derived ADM2 plays a role in regulating hormonal response and follicle growth [4].

In conclusion, Adm2 is involved in various biological functions, including lipid metabolism, embryo development, and ovarian function. The study of Adm2 using KO or conditional knockout (CKO) mouse models has provided insights into its role in diseases such as NAFLD, highlighting its potential as a therapeutic target.