Klf10, also known as TGFβ-inducible early gene-1 (TIEG1), is a DNA-binding transcriptional regulator with a triple C2H2 zinc finger domain. It is a downstream factor of the transforming growth factor-β (TGF-β)/SMAD signaling pathway and is involved in multiple biological functions, such as glucose and lipid metabolism, cell proliferation, apoptosis, and differentiation. It plays a crucial role in various physiological and pathophysiological processes [3,4]. Genetic models, especially gene knockout (KO) mouse models, have been instrumental in studying Klf10's functions.

In non-alcoholic steatohepatitis (NASH), hepatocyte-specific knockout of Klf10 (Klf10LKO) in NASH diet-fed mice increases lipid accumulation, cell death, inflammation, and fibrosis, reducing the protective effects of treadmill exercise against NASH. In contrast, hepatocyte-specific overexpression of Klf10 (Klf10LTG) works with exercise to reduce NASH. Klf10 promotes the expression of fumarate hydratase 1 (Fh1), reducing fumarate accumulation, which decreases H3K4me3 levels on lipogenic gene promoters to attenuate lipogenesis [1]. In cancer cachexia, deletion of KLF10 rescues cancer-induced muscle wasting, and it binds key atrophy genes associated with muscle atrophy in vitro. A TGF-β/KLF10 signaling axis regulates atrophy-associated genes to induce muscle wasting in pancreatic cancer [2,5].

In summary, Klf10 is a critical signaling mediator in various biological processes. Model-based research, especially using KO mouse models, has revealed its roles in NASH and cancer cachexia. In NASH, it is a downstream effector of exercise in combating the disease, and in cancer cachexia, it is involved in muscle wasting, providing potential therapeutic targets for these diseases.