Tissue specific regulation of thyroid hormone action
While the HPT axis warrants the stability of circulating thyroid hormone levels, a complex machinery of thyroid hormone transporters, metabolizing enzymes, receptors and co-regulators ensures that the local thyroid hormone action meets the highly variable requirements of the different tissues.
Central regulation of the hypothalamic-pituitary-thyroid (HPT) axis
The hypothalamic-pituitary-thyroid (HPT) axis primarily functions to maintain normal, circulating levels of thyroid hormones that are essential for the biologic function of all tissues including brain development, regulation of cardiovascular, bone and liver function, food intake and energy expenditure among many others.
Regulation of energy homeostasis by GLP-1 receptive neuronal networks
Glucagon-like peptide-1 (GLP-1) is an incretin hormone. It is derived from the posttranslational processing of proglucagon. This prohormone is synthesized by three cell populations, the neuroendocrine L cells of the intestinal mucosa, the ß cells of the pancreatic Langerhans islands and in a neuronal population located in the nucleus tractus solitarii (NTS) and intermediate reticular nucleus of the medulla oblongata.
GLP-1 is produced, however, only in the gut and the brain as its production requires PC1/3 catalyzed posttranslational processing of proglucagon. GLP-1 has a critical role in the regulation of energy and glucose homeostasis, and exerts its effects via the GLP-1 receptor (GLP-1R). It decreases circulating glucose levels by slowing down the gastric emptying, and by stimulating insulin production and inhibiting glucagon secretion. Furthermore, GLP-1 has potent inhibitory effect on food intake, and can decrease the hedonic value of food and the motivation to eat. These properties have made GLP-1R an important drug target in the field of type 2 diabetes and obesity. Long acting GLP-1 agonists, liraglutide, semaglutide and dulaglutide have been marketed for the treatment of type two diabetes, while liraglutide is approved for the treatment of obesity. Despite of the widespread use of these GLP-1 analogues, it is not clear, how their effects are mediated on the energy homeostasis via the brain.
To uncover the neuronal elements that mediate the effects of GLP-1 signaling on the energy expenditure, we map the GLP-1R-containing elements in the brain and spinal cord, identify the chemotype and connectivity of these neuronal groups and using cell type specific GLP-1R KO animals, we determine the role of these neuronal groups in the regulation of energy homeostasis and in the mediation of the effects of GLP-1 signaling on the energy homeostasis.
The major goal of the Laboratory is to elucidate the anatomy and physiology of the neuronal networks involved in the central regulation of the energy homeostasis in rodents and humans.
