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Authors & Affiliations
Andreea Constantinescu, Luca Höhne, Jens Mittag, Markus Schwaninger, Helge Müller-Fielitz
Abstract
Thermogenesis is a vital physiological process that contributes to maintaining energy homeostasis, metabolic health, and adaptation to environmental changes. Central for metabolic regulation is the hypothalamus, orchestrating a diverse array of neuroendocrine systems. Within this intricate network, the role of thyrotropin-releasing hormone (TRH) neurons of the hypothalamus is unknown. Our project aimed to delineate TRH populations implicated in modulating brown adipose tissue (BAT)-derived thermogenesis. Employing an exploratory approach utilizing retrograde tracers from BAT, we pinpointed three key hypothalamic nuclei: the paraventricular hypothalamus (PVH), dorsomedial hypothalamus (DMH), and medial preoptic area (MPA). These nuclei harbor substantial TRH populations and provide multisynaptic connections to the BAT. Using TRH-IRES-Cre mouse lines together with chemogenetic tools, we performed calorimetric and thermographic measurements following specific activation of different TRH populations. We were able to show that PVH and DMH residing TRH neurons regulate energy expenditure and BAT thermogenesis independently of the HPT axis activation. While MPA-residing TRH neurons do not induce thermogenesis of BAT, however they influence energy expenditure and feeding behavior. Our findings highlight the pivotal role of TRH neuronal signaling in modulating calorie intake and energy expenditure, extending beyond its conventional association with the HPT axis. This research sheds light on the complex interplay between hypothalamic circuits and thermogenic processes, with implications for understanding and potentially treating metabolic disorders.