Creb3l3-flox Mouse

Creb3l3, also known as cAMP responsive element-binding protein 3 like 3, is a membrane-bound transcription factor. It is crucial for maintaining lipid metabolism in the liver and small intestine. It controls hepatic triglyceride and glucose metabolism via activating plasma fibroblast growth factor 21 (FGF21) and lipoprotein lipase. It is also involved in pathways related to fatty acid oxidation and ketogenesis, and is important for systemic energy homeostasis [1,3,4,6]. Genetic models, such as gene knockout (KO) and conditional knockout (CKO) mouse models, have been used to study its functions.

In KO mouse models, Creb3l3-deficient LDLR-/-mice showed exacerbated hyperlipidemia and enhanced aortic atheroma formation, while hepatic nuclear Creb3l3 overexpression suppressed atherosclerosis and improved hyperlipidemia. Creb3l3 directly up-regulates anti-atherogenic FGF21 and APOA4, and antagonizes hepatic sterol regulatory element-binding protein (SREBP)-mediated lipogenic and cholesterogenic genes [1]. Fat-specific ablation of Creb3l3 in mice enhanced weight gain and insulin resistance after high-fat feeding, while inguinal fat Creb3l3 overexpression deterred diet-induced obesity and improved metabolic dysfunction [2]. Creb3l3-/-mice on a ketogenic-diet had reduced expression of genes for fatty oxidation and ketogenesis, similar to Ppara-/-mice [4].

In conclusion, Creb3l3 plays essential roles in lipid and energy metabolism, as revealed through model-based research. KO and CKO mouse models have demonstrated its significance in diseases like atherosclerosis, obesity, and severe hypertriglyceridemia, providing insights into its potential as a therapeutic target for these metabolic disorders [1,2,5].