Obesity

Ana Domingos

The laboratory led by Ana Domingos researches on neuroimmune mechanisms underlying obesity. They discovered the sympathetic neuro-adipose junction, a functional synapse-like connection between white adipocytes and the sympathetic nervous system (Cell 2015).

Researchers also found that this neuro-adipose junction is necessary and sufficient for fat mass reduction via norepinephrine (NE) signaling (Cell 2015, Nature Comm 2017).

They then discovered Sympathetic neuron-Associated Macrophages (SAMs) that directly import and metabolize NE.

Abrogation of SAM function promotes long-term amelioration of obesity independently of food intake (Nature Medicine, 2017).

Publications

Pirzgalska, R.M., Seixas, E., Seidman, J.S., Link, V.M., Sánchez, N.M., Mahú, I., Mendes, R., Gres, V., Kubasova, N., Morris, I., Arús, B.A., Larabee, C.M., Vasques, M., Tortosa, F., Sousa, A.L., Anandan, S., Tranfield, E., Hahn, M.K., Iannacone, M., Spann, N.J., Glass, C.K., Domingos, A.I. (2017) Sympathetic neuron-associated macrophages contribute to obesity by importing and metabolizing norepinephrine. Nat Med. 14, pp. : [Epub ahead of print]
Pereira, M.M.A., Mahú, I., Seixas, E., Martinéz-Sánchez, N., Kubasova, N., Pirzgalska, R.M., Cohen, P., Dietrich, M.O., López, M., Bernardes, G.J.L., Domingos, A.I. (2017) A brain-sparing diphtheria toxin for chemical genetic ablation of peripheral cell lineages. Nat Commun. 8 : 14967

Reis, B.S., Lee, K., Fanok, M.H., Mascaraque, C., Amoury, M., Cohn, L.B., Rogoz, A., Danner, O.S., Moraes-Vieira, P.M., Domingos, A.I., Mucida, D. (2015) Leptin receptor signaling in T cells is required for Th17 differentiation. J Immunol. 194 : 5253-5260
Kubasova, N., Burdakov, D., Domingos, A.I. (2015) Sweet and low on leptin: hormonal regulation of sweet taste buds. Diabetes. 64 : 3651-3652
Sano, T., Huang, W., Hall, J.A., Yang, Y., Chen, A., Gavzy, S.J., Lee, J., Ziel, J.W., Miraldi, E.R., Domingos, A.I., Bonneau, R., Littman, D.R. (2015) An IL-23R/IL-22 circuit regulates epithelial serum amyloid a to promote local effector Th17 responses. Cell. 163 : 381-393
Huang, W., Thomas, B., Flynn, R.A., Gavzy, S.J., Wu, L., Kim, S.V., Hall, J.A., Miraldi, E.R., Ng, C.P., Rigo, F.W., Meadows, S., Montoya, N.R., Herrera, N.G., Domingos, A.I., Rastinejad, F., Myers, R.M., Fuller-Pace, F.V., Bonneau, R., Chang, H.Y., Acuto, O., Littman, D.R. (2015) DDX5 and its associated lncRNA RMRP modulate Th17 cell effector functions. Nature. 528 : 517-522
Zeng, W., Pirzgalska, R.M., Pereira, M.M.A., Kubasova, N., Barateiro, A., Seixas, E., Lu, Y., Kozlova, A., Voss, H., Martins, G.G., Friedman, J.M., Domingos, A.I. (2015) Sympathetic neuro-adipose connections mediate leptin-driven lipolysis. Cell. 163 : 84-94
Stanley, S., Domingos, A.I., Kelly, L., Garfield, A., Damanpour, S., Heisler, L., Friedman, J.M. (2013) Profiling of glucose-sensing neurons reveals that GHRH neurons are activated by hypoglycemia Cell Metabol. 18(4) : 596-607
Chaudhury, D.*, Walsh, J.J.,*, Friedman, A.K., Juarez, B., Ku, S.M., Koo, J.W., Ferguson, D., Tsai, H., Pomeranz, L., Christoffel, D.J., Nectow, A. R., Domingos, A.I., Mazie-Robison, M., Mouzon, E., Lobo, M.K., Neve, R.L., Friedman, J.M., Russo, S.J., Deisseroth, K., Nestler, E.J., Han, M.H. *(equal contribution) (2012) Rapid regulation of depression-related behaviors by control of midbrain dopamine neuronNature 493 (7433) : 532-6
Domingos A.I., Vaynshteyn, J., Voss, H., Ren, X., Gradinaru, V., Zhang, F., Deisseroth, K., de Araujo, I.E., Friedman, J.M. (2011) Sympathetic Neuro-Adipose Connections Mediate Leptin-Driven Lipolysis Nat Neurosc. 14 : 1562–1568