Venue: Centre Broca
The seminar will be a recording, broadcast in the auditorium, and followed by Q&A at 2:15pm with the speaker on Zoom (still in the audiorium).
My laboratory researches neurobiological mechanisms underlying obesity. First, we discovered neuro-adipose junctions between white adipocytes and sympathetic neurons that constitute a peripheral effector arm of leptin action in the brain (1). Moreover, we discovered that this efferent arm is negatively regulated by Sympathetic neuron-Associated Macrophages (SAMs) that import NE via the Slc6a2 transporter resulting in its clearance. Abrogation of SAM function promotes long-term mitigation of obesity independently of food intake (2). These findings inspired the development of a new class of anti-obesity compounds named sympathofacilitators, designed not to enter the brain. Consequently, they do not have the typical cardiovascular side effects of centrally acting sympathomimetic drugs (3). Sympathofacilitator drugs act as an energy sink by coupling thermogenesis to active heat dissipation via the beta2 adrenergic receptor, independently of food intake. Whereas druggability intersects our discovery path, the overall focus of this talk are the fundamental aspects of sympathetic-nerve biology in the context of obesity and metabolic dysfunction. We have coined the term Neuroimmunometabolism to designate the study of the crosstalk between immune cells and neurons controlling whole-body metabolism. Neuroimmunometabolic mechanisms linking inflammation to SNS neuronal function, and leptin resistance will be discussed (4).
1) Zeng W*, Pirzgalska RM*; Pereira MMA; Kubasova N; Barateiro A; Seixas E; Lu YH; Kozlova A; Voss H; Martins GG; Friedman JM, Domingos AIψ (2015). Sympathetic Neuro-Adipose Connections Mediate Leptin-Driven Lipolysis. Cell. 163(1):84–94,
2)Roksana M Pirzgalska*,Elsa Seixas*,Jason S Seidman, Verena M Link, Noelia Martínez Sánchez, Inês Mahú, Raquel Mendes, Vitka Gres, Nadiya Kubasova, Imogen Morris, Bernardo A Arús, Chelsea M Larabee, Miguel Vasques, Francisco Tortosa, Ana L Sousa, Sathyavathy Anandan, Erin Tranfield, Maureen K Hahn, Matteo Iannacone, Nathanael J Spann, Christopher K Glass & Ana I Domingos ψ (2017). Sympathetic neuron–associated macrophages contribute to obesity by importing and metabolizing norepinephrine. Nature Medicine.
3) Brain-sparing sympathofacilitators mitigate obesity without adverse cardiovascular effects.
Mahú I, Barateiro A, Rial-Pensado E, Martinéz-Sánchez N, Vaz SH, Cal PMSD, Jenkins B, Rodrigues T, Cordeiro C, Costa MF, Mendes R, Seixas E, Pereira MMA, Kubasova N, Gres V, Morris I, Temporão C, Olivares M, Sanz Y, Koulman A, Corzana F, Sebastião AM, López M, Bernardes GJL, Domingos AI, Cell Metabolism June 2nd;31(6):1120-1135 (2020)
4) Domingos, A.I. Leptin: a missing piece in the immunometabolism puzzle. Nature Rev Immunol 20, 3 (2020).
Organized by Bordeaux Neurocampus, NBA and Bordeaux Neurocampus Graduate Program
Associate Professor of Neuroscience
Dept. Physiology, Anatomy, Genetics
University of Oxford.
HHMI / Wellcome IRScholar