Sympathetic neuromodulation of adipose tissue function

Sympathetic neuromodulation of adipose tissue function

BAT_opto

 

Through our integrative physiology approach we identified novel functional roles of sympathetic nerves and nerve-derived factors (neurotransmitters and neuropeptides) in adipose tissue functions. This line of research led to the identification of the synergism between norepinephrine/beta-adrenergic receptor signaling and the neuropeptide TLQP-21/C3aR1 signaling in lipolysis in white adipocytes, as well as between norepinephrine/beta-adrenergic receptor signaling and ATP/purinergic receptors signaling in adipogenesis and uncoupling in brown adipocytes. We also developed innovative optogenetic and neuromodulation approaches designed to achieve selective sympathetic stimulation of adipose fat pads to modulate organ functions with the ultimate goal of preventing and treating obesity and diabetes.

relevant_publications

Relevant publications

Lipolysis drives expression of the constitutively active receptor GPR3 to induce adipose thermogenesis. Sveidahl Johansen O, Ma T, Hansen JB, Markussen LK, Schreiber R, Reverte-Salisa L, Dong H, Christensen DP, Sun W, Gnad T, Karavaeva I, Nielsen TS, Kooijman S, Cero C, Dmytriyeva O, Shen Y, Razzoli M, O'Brien SL, Kuipers EN, Nielsen CH, Orchard W, Willemsen N, Jespersen NZ, Lundh M, Sustarsic EG, Hallgren CM, Frost M, McGonigle S, Isidor MS, Broholm C, Pedersen O, Hansen JB, Grarup N, Hansen T, Kjær A, Granneman JG, Babu MM, Calebiro D, Nielsen S, Rydén M, Soccio R, Rensen PCN, Treebak JT, Schwartz TW, Emanuelli B, Bartolomucci A, Pfeifer A, Zechner R, Scheele C, Mandrup S, Gerhart-Hines Z.Cell. 2021 Jun 24;184(13):3502-3518.e33. doi:
10.1016/j.cell.2021.04.037. Epub 2021 May 27. PMID: 34048700; PMCID: PMC8238500.

Optogenetic-induced sympathetic neuromodulation of brown adipose tissue thermogenesis. Lyons CE, Razzoli M, Larson E, Svedberg D, Frontini A, Cinti S, Vulchanova L, Sanders M, Thomas M, Bartolomucci A.FASEB J. 2020
Feb;34(2):2765-2773. doi: 10.1096/fj.201901361RR. Epub 2019 Dec 23. PMID:
31908033; PMCID: PMC7306786.

β-Adrenergic receptors control brown adipose UCP-1 tone and cold response without affecting its circadian rhythmicity. Razzoli M, Emmett MJ, Lazar MA, Bartolomucci A. FASEB J. 2018 Oct;32(10):5640-5646. doi:
10.1096/fj.201800452R. Epub 2018 May 1. PMID: 29715048; PMCID: PMC6133705.

Stress-induced activation of brown adipose tissue prevents obesity in conditions of low adaptive thermogenesis. Razzoli M, Frontini A, Gurney A, Mondini E, Cubuk C, Katz LS, Cero C, Bolan PJ, Dopazo J, Vidal-Puig A, Cinti S, Bartolomucci A. Mol Metab. 2015 Nov 11;5(1):19-33. doi: 10.1016/j.molmet.2015.10.005. PMID: 26844204; PMCID: PMC4703853.