Cers1, short for ceramide synthase 1, is a key enzyme in the de novo sphingolipid synthesis pathway. It is responsible for generating C18:0 ceramide, a central molecule in sphingolipid metabolism that has important functions in membrane structure and cellular signaling [1,2,3,4]. The sphingolipid biosynthesis pathway, in which Cers1 is involved, is crucial for various biological processes such as cell differentiation, apoptosis, and mitochondrial function [1,6]. Genetic models, like gene knockout (KO) or conditional knockout (CKO) mouse models, have been valuable in studying Cers1's functions.

In skeletal muscle, Cers1 seems to play a significant role in age-related muscle function and insulin resistance. Inhibition of Cers1 in aged mice, either pharmacologically or genetically, exacerbates age-related muscle dysfunction, including blunted myogenesis, deteriorated muscle mass and function, along with features of inflammation and fibrosis [2]. Additionally, mice lacking Cers1, either globally or specifically in skeletal muscle (CerS1ΔSkM), show reduced muscle C18:0 ceramide content and improved systemic glucose homeostasis, protecting against obesity-induced insulin resistance [3]. In hypophysoma, over-expression of Cers1 by lentivirus can inhibit the development of hypophysoma in vivo and in vitro, possibly by enhancing autophagy through the PI3K/AKT signaling pathway [5].

In conclusion, Cers1 is essential in regulating sphingolipid metabolism with far-reaching impacts on multiple biological processes. Model-based research, especially using KO/CKO mouse models, has revealed its crucial roles in age-related muscle homeostasis and insulin resistance-associated diseases. Understanding Cers1 provides insights into the mechanisms underlying these conditions and may offer potential therapeutic targets.