Acute reciprocal regulation of adiponectin and leptin
Final Report Abstract
During this DFG Research Fellowship, I aimed to explore the reciprocal regulation of leptin and adiponectin. The initially proposed mouse models of inducible genetic deletion of leptin receptor (Lepr) or adiponectin receptor (Adipor) were not suitable for addressing the question. While the Adipor1/2 double KO line had a baseline adipose tissue phenotype, knocking out the Lepr in adipocytes was dismissed due to the lack of Lepr transcripts in adipocytes. With the development of a Leptin over-expressing adeno-associated virus (AAV), I tried to create an alternative mouse model that would allow the time-resolved study of reciprocal regulation of leptin and adiponectin. To our surprise, even a strong increase in leptin did not alter the adiponectin level at an early stage. This leads us to conclude, that there is no reciprocal regulation of leptin and adiponectin. Nevertheless, we thought to study at least the effect that adiponectin has on the adipose tissue physiology in absence of Leptin by applying the Adipoq/LepAi-DKO Mouse. While the leptin knockout in adipocytes showed the expected effect of expanding the adipose tissue, the amount of adiponectin left in circulation did not have any impact on that phenotype. During the course of the leptin over-expression experiment, an interesting new hypothesis about the destination of de-differentiating adipocytes was postulated. I am still in the process of acquiring additional data in preparation of a future publication on the character of de-differentiated adipocytes. Apart from my training in the production of adeno-associated viruses and creation of new genetic mouse models, this DFG Research Fellowship also allowed me to establish close connections with brilliant researchers from the Scherer lab. Close collaboration with several of my colleagues already resulted in important research publications. Long-term collaborations were started. The teaching of project planning and scientific management by my mentor Philipp E. Scherer helped me to contributing to the Endocrinology research field by two key publications in which we evaluated decade long research. More research papers are about to be published to conclude this fruitful stay in the Scherer Lab.
Publications
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Adipocyte iron levels impinge on a fat-gut crosstalk to regulate intestinal lipid absorption and mediate protection from obesity. Cell Metabolism, 33(8), 1624-1639.e9.
Zhang, Zhuzhen; Funcke, Jan-Bernd; Zi, Zhenzhen; Zhao, Shangang; Straub, Leon G.; Zhu, Yi; Zhu, Qingzhang; Crewe, Clair; An, Yu A.; Chen, Shiuhwei; Li, Na; Wang, May-yun; Ghaben, Alexandra L.; Lee, Charlotte; Gautron, Laurent; Engelking, Luke J.; Raj, Prithvi; Deng, Yingfeng; Gordillo, Ruth; ... & Scherer, Philipp E.
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Adipose tissue hyaluronan production improves systemic glucose homeostasis and primes adipocytes for CL 316,243-stimulated lipolysis. Nature Communications, 12(1).
Zhu, Yi; Li, Na; Huang, Mingyang; Bartels, Mason; Dogné, Sophie; Zhao, Shangang; Chen, Xi; Crewe, Clair; Straub, Leon; Vishvanath, Lavanya; Zhang, Zhuzhen; Shao, Mengle; Yang, Yongjie; Gliniak, Christy M.; Gordillo, Ruth; Smith, Gordon I.; Holland, William L.; Gupta, Rana K.; Dong, Bingning; ... & Scherer, Philipp E.
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Insulin sensitive human adipocytes for in vitro studies. Nature Reviews Endocrinology, 18(10), 591-592.
Straub, Leon G. & Scherer, Philipp E.
