Igfbp4, Insulin-like growth factor-binding protein 4, is highly expressed in adipocytes and osteoblasts. It binds to insulin-like growth factors (IGFs) and is inhibitory of IGFs in vitro. It is involved in the IGF-related pathway, which is crucial for growth, development, and metabolism. Genetic models, such as knockout mice, can be valuable for studying its functions [4].

In Igfbp4 null mice (Igfbp4-/ -), inguinal and gonadal white adipose tissue had decreased weights and Pparγ expression. Primary bone marrow stromal cells and ear mesenchymal stem cells from these mutant mice showed reduced adipogenesis. Also, on a high-fat diet, there were sexual differences in adipocyte expansion. Igfbp4 was required for inguinal fat expansion in female mice but not in male mice [4]. In patients with type 2 diabetes (T2D), higher levels of total and intact Igfbp4 were associated with all-cause mortality [1]. In chronic lymphocytic leukemia (CLL), Igfbp4 was identified as an independent prognostic factor [2]. In cervical cancer-originated HeLa cells, lncRNA-Igfbp4 was found to suppress autophagy through ULK1/Beclin1 signaling [3].

In conclusion, Igfbp4 plays essential roles in adipogenesis, influencing adipose depot distribution, and is associated with mortality in T2D and prognosis in CLL. The Igfbp4 null mouse model has been instrumental in revealing its role in adipogenesis. These findings contribute to understanding biological processes and disease mechanisms related to Igfbp4, potentially providing new insights for disease treatment and prevention.

References:

1. Gude, Mette Faurholdt, Hjortebjerg, Rikke, Bjerre, Mette, Sandbæk, Annelli, Frystyk, Jan. 2023. The STC2-PAPP-A-IGFBP4-IGF1 axis and its associations to mortality and CVD in T2D. In Endocrine connections, 12, . doi:10.1530/EC-22-0451. https://pubmed.ncbi.nlm.nih.gov/36607154/

2. Shi, Yuye, Xu, Xiaohu, He, Zhengmei, Wang, Chunling, Yu, Liang. 2023. AKAP12 and IGFBP4 Are Prognostic Factors for Chronic Lymphocytic Leukemia. In Acta haematologica, 146, 474-481. doi:10.1159/000530618. https://pubmed.ncbi.nlm.nih.gov/37605556/

3. Zhang, Lei, Zhang, Zongshan, Li, Erwei, Xu, Poshi. 2022. c-Myc-Regulated lncRNA-IGFBP4 Suppresses Autophagy in Cervical Cancer-Originated HeLa Cells. In Disease markers, 2022, 7240646. doi:10.1155/2022/7240646. https://pubmed.ncbi.nlm.nih.gov/36072894/

4. Maridas, David E, DeMambro, Victoria E, Le, Phuong T, Mohan, Subburaman, Rosen, Clifford J. . IGFBP4 Is Required for Adipogenesis and Influences the Distribution of Adipose Depots. In Endocrinology, 158, 3488-3500. doi:10.1210/en.2017-00248. https://pubmed.ncbi.nlm.nih.gov/28938423/