What is your presentation about?
I will discuss the recently discovered role for the LepR:EGFR complex in the transport of peripheral leptin into the metabolic brain by hypothalamic tanycytes, with important implications for the pathophysiology of not only obesity but type 2 diabetes. Tanycytes are glial cells lining the floor of the third ventricle and constitute the gateway of blood-borne metabolic signals into the brain. We have previously shown that median eminence tanycytes shuttle leptin across the blood-brain barrier via an ERK-dependent signaling pathway. However, the putative involvement of LepR in this process has remained unclear, with some authors questioning the expression of LepR by tanycytes. Here, I will demonstrate that LepR is not only expressed but is functionally active in hypothalamic median eminence tanycytes and that activation of the LepR:EGFR complex is required for the transcytotic transport of leptin towards neurons in the arcuate nucleus of the hypothalamus. Furthermore, this process plays a vital role in the central control of pancreatic β-cell function and lipid accumulation, with therapeutic repercussions.
What makes this topic important in 2022?
Because of widespread interest in the role of leptin in the central control of glucose homeostasis and more broadly, in the mechanisms underlying hormone resistance in metabolic diseases, we anticipate that these results will be of considerable interest to the wide audience of the ADA meeting.
How did you become involved with this area of diabetes research or care?
By serendipity, i.e., I was not expecting that preventing the transport of leptin into the hypothalamus by tanycytes in adults would result in pancreatic beta cell failure…!
What are you most looking forward to at the 82nd Scientific Sessions?
Interact with leading researchers and clinicians in the field of diabetes and possibly develop new collaborations.