Hadha-KO Mouse

HADHA, also known as hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha, is a key mitochondrial β-oxidation enzyme. It is involved in fatty acid oxidation (FAO) pathway [3,4,8], which is crucial for energy production in cells. HADHA also plays a role in regulating metabolic processes such as ketone body production and is associated with multiple biological functions and disease-related pathways [1].

In various disease models, HADHA has shown significant impacts. In mice, liver-specific HADHA overexpression reversed hepatic gluconeogenesis, while knockdown augmented glucagon response, suggesting its role in diabetes-related metabolic regulation [1]. In hepatocellular carcinoma, miR-612 regulated invadopodia formation via HADHA-mediated lipid reprogramming, affecting cancer cell metastasis [2]. In ovarian cancer, HADHA overexpression was associated with poor survival, and its knockdown hindered cell growth and migration [5]. In glioma, high HADHA expression was linked to malignant progression, and knocking down HADHA decreased cell proliferation and migration [6]. In non-alcoholic fatty liver disease (NAFLD), HADHA alleviated hepatic steatosis and oxidative stress by inactivating the MKK3/MAPK pathway [7]. In regulatory T cells, Zfp335 controlled eTreg differentiation by regulating FAO through targeting HADHA, establishing immune tolerance [8]. In HTR-8/SVneo cells, HADHA inhibited cell migration and invasion by regulating the PI3K/AKT signaling pathway [9].

In conclusion, HADHA is essential for metabolic regulation through its role in fatty acid oxidation and ketone body production. Studies using gene knockout or knockdown models in mice and cell lines have revealed its significance in diseases such as diabetes, various cancers, NAFLD, and immune-related disorders. Understanding the function of HADHA provides potential targets for therapeutic interventions in these disease areas.