PMID- 29379096 OWN - NLM STAT- MEDLINE DCOM- 20181211 LR - 20190129 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 8 IP - 1 DP - 2018 Jan 29 TI - The antidepressant fluoxetine acts on energy balance and leptin sensitivity via BDNF. PG - 1781 LID - 10.1038/s41598-018-19886-x [doi] LID - 1781 AB - Leptin and Brain Derived Neurotrophic Factor (BDNF) pathways are critical players in body weight homeostasis. Noninvasive treatments like environmental stimulation are able to increase response to leptin and induce BDNF expression in the brain. Emerging evidences point to the antidepressant selective serotonin reuptake inhibitor Fluoxetine (FLX) as a drug with effects similar to environmental stimulation. FLX is known to impact on body weight, with mechanisms yet to be elucidated. We herein asked whether FLX affects energy balance, the leptin system and BDNF function. Adult lean male mice chronically treated with FLX showed reduced weight gain, higher energy expenditure, increased sensitivity to acute leptin, increased hypothalamic BDNF expression, associated to changes in white adipose tissue expression typical of "brownization". In the Ntrk2(tm1Ddg)/J model, carrying a mutation in the BDNF receptor Tyrosine kinase B (TrkB), these effects are partially or totally reversed. Wild type obese mice treated with FLX showed reduced weight gain, increased energy output, and differently from untreated obese mice, a preserved acute response to leptin in terms of activation of the intracellular leptin transducer STAT3. In conclusion, FLX impacts on energy balance and induces leptin sensitivity and an intact TrkB function is required for these effects to take place. FAU - Scabia, Gaia AU - Scabia G AUID- ORCID: 0000-0002-1603-4585 AD - Obesity Center at the Endocrinology Unit, Department of Clinical and Experimental Medicine, Via Paradisa 2, 56126, Pisa, Italy. AD - Institute of Clinical Physiology, Italian National Research Council, Via Moruzzi 1, 56124, Pisa, Italy. FAU - Barone, Ilaria AU - Barone I AD - Dulbecco Telethon Institute, Via Varese, 16B, Rome, 00185, Italy. AD - Laboratory of Neurobiology, Scuola Normale Superiore, Piazza dei Cavalieri 7, 56100, Pisa, Italy. FAU - Mainardi, Marco AU - Mainardi M AD - Institute of Neuroscience, Italian National Research Council, Via Moruzzi, 56124, Pisa, Italy. AD - Laboratory of Neurobiology, Scuola Normale Superiore, Piazza dei Cavalieri 7, 56100, Pisa, Italy. FAU - Ceccarini, Giovanni AU - Ceccarini G AD - Obesity Center at the Endocrinology Unit, Department of Clinical and Experimental Medicine, Via Paradisa 2, 56126, Pisa, Italy. FAU - Scali, Manuela AU - Scali M AD - Institute of Neuroscience, Italian National Research Council, Via Moruzzi, 56124, Pisa, Italy. FAU - Buzzigoli, Emma AU - Buzzigoli E AD - Institute of Clinical Physiology, Italian National Research Council, Via Moruzzi 1, 56124, Pisa, Italy. FAU - Dattilo, Alessia AU - Dattilo A AD - Obesity Center at the Endocrinology Unit, Department of Clinical and Experimental Medicine, Via Paradisa 2, 56126, Pisa, Italy. FAU - Vitti, Paolo AU - Vitti P AD - Obesity Center at the Endocrinology Unit, Department of Clinical and Experimental Medicine, Via Paradisa 2, 56126, Pisa, Italy. FAU - Gastaldelli, Amalia AU - Gastaldelli A AUID- ORCID: 0000-0003-2594-1651 AD - Institute of Clinical Physiology, Italian National Research Council, Via Moruzzi 1, 56124, Pisa, Italy. FAU - Santini, Ferruccio AU - Santini F AD - Obesity Center at the Endocrinology Unit, Department of Clinical and Experimental Medicine, Via Paradisa 2, 56126, Pisa, Italy. FAU - Pizzorusso, Tommaso AU - Pizzorusso T AUID- ORCID: 0000-0001-5614-0668 AD - Institute of Neuroscience, Italian National Research Council, Via Moruzzi, 56124, Pisa, Italy. AD - Dipartimento NEUROFARBA, Universita di Firenze, via di San Savi, 26, 50235, Firenze, Italy. FAU - Maffei, Lamberto AU - Maffei L AD - Institute of Neuroscience, Italian National Research Council, Via Moruzzi, 56124, Pisa, Italy. FAU - Maffei, Margherita AU - Maffei M AD - Obesity Center at the Endocrinology Unit, Department of Clinical and Experimental Medicine, Via Paradisa 2, 56126, Pisa, Italy. m.maffei@ifc.cnr.it. AD - Institute of Clinical Physiology, Italian National Research Council, Via Moruzzi 1, 56124, Pisa, Italy. m.maffei@ifc.cnr.it. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180129 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Antidepressive Agents) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Leptin) RN - 01K63SUP8D (Fluoxetine) RN - EC 2.7.10.1 (Receptor, trkB) SB - IM MH - Adipose Tissue, White/drug effects/metabolism MH - Animals MH - Antidepressive Agents/*pharmacology MH - Body Weight/drug effects MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Energy Metabolism/*drug effects MH - Fluoxetine/*pharmacology MH - Leptin/*pharmacology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Obesity/metabolism MH - Receptor, trkB/metabolism MH - Weight Gain/drug effects PMC - PMC5789051 COIS- The authors declare that they have no competing interests. EDAT- 2018/01/31 06:00 MHDA- 2018/12/12 06:00 PMCR- 2018/01/29 CRDT- 2018/01/31 06:00 PHST- 2017/05/31 00:00 [received] PHST- 2018/01/08 00:00 [accepted] PHST- 2018/01/31 06:00 [entrez] PHST- 2018/01/31 06:00 [pubmed] PHST- 2018/12/12 06:00 [medline] PHST- 2018/01/29 00:00 [pmc-release] AID - 10.1038/s41598-018-19886-x [pii] AID - 19886 [pii] AID - 10.1038/s41598-018-19886-x [doi] PST - epublish SO - Sci Rep. 2018 Jan 29;8(1):1781. doi: 10.1038/s41598-018-19886-x.