Vegfb, short for vascular endothelial growth factor B, is a key member of the VEGF family. It binds specifically to Vascular Endothelial Growth Factor Receptor 1 (VEGFR1), and is involved in regulating multiple biological functions such as vascular biological function, lipid and glucose metabolism, and myoblast proliferation and differentiation. The PI3K/AKT, AMPK, and p38 MAPK signaling pathways are among those associated with Vegfb [1,2,3,4]. Genetic models, especially knockout mouse models, have been crucial in studying Vegfb's functions.

In gene knockout studies, systemic Vegfb knockout in mice led to increased body fat, serum lipoprotein, NAFLD score, and insulin resistance, along with reduced fatty acid oxidation and increased lipid synthesis, indicating Vegfb's role in NAFLD lipid metabolism and insulin resistance through the AMPK signaling pathway [3]. Knockdown of Vegfb decreased body weight and iWAT index, stimulated white adipose tissue browning, and increased skeletal muscle growth, suggesting its role in fat deposition and muscle development [5]. Ablation of adipocyte Vegfb resulted in deficiency in murine white adipose tissue browning, while Vegfb supplementation promoted thermogenesis [4].

In conclusion, Vegfb plays essential roles in lipid and glucose metabolism, adipose tissue thermogenesis, and skeletal muscle development. Studies using Vegfb knockout mouse models have significantly enhanced our understanding of its functions in diseases like NAFLD, obesity, and related metabolic disorders, providing potential targets for therapeutic interventions.

References:

1. Li, Yuqi, Li, Wenhao, Zhu, Xiaonan, Xu, Fang, Li, Yana. 2024. VEGFB ameliorates insulin resistance in NAFLD via the PI3K/AKT signal pathway. In Journal of translational medicine, 22, 976. doi:10.1186/s12967-024-05621-w. https://pubmed.ncbi.nlm.nih.gov/39468621/

2. Ling, Mingfa, Quan, Lulu, Lai, Xumin, Jiang, Qingyan, Wang, Songbo. 2021. VEGFB Promotes Myoblasts Proliferation and Differentiation through VEGFR1-PI3K/Akt Signaling Pathway. In International journal of molecular sciences, 22, . doi:10.3390/ijms222413352. https://pubmed.ncbi.nlm.nih.gov/34948148/

3. Li, Rongrong, Li, Yuqi, Yang, Xueling, Yu, Haining, Li, Yana. 2022. Reducing VEGFB accelerates NAFLD and insulin resistance in mice via inhibiting AMPK signaling pathway. In Journal of translational medicine, 20, 341. doi:10.1186/s12967-022-03540-2. https://pubmed.ncbi.nlm.nih.gov/35907871/

4. Wang, Lei, Jin, Jing, Zhang, Nuo, Chen, Qi, Zhu, Xudong. 2024. VEGFB promotes adipose tissue thermogenesis by inhibiting norepinephrine clearance in macrophages. In Biochimica et biophysica acta. Molecular basis of disease, 1871, 167536. doi:10.1016/j.bbadis.2024.167536. https://pubmed.ncbi.nlm.nih.gov/39378967/

5. Ling, Mingfa, Lai, Xumin, Quan, Lulu, Jiang, Qingyan, Wang, Songbo. 2022. Knockdown of VEGFB/VEGFR1 Signaling Promotes White Adipose Tissue Browning and Skeletal Muscle Development. In International journal of molecular sciences, 23, . doi:10.3390/ijms23147524. https://pubmed.ncbi.nlm.nih.gov/35886871/