OBJECTIVE: Loss of BDNF-TrkB signaling results in obesity in both humans and mice; however, the neural circuit that mediates this effect is unknown. The role of TrkB signaling in dopamine-1 receptor expressing neurons in body weight regulation was tested. METHODS: Mice with a floxed allele of the TrkB gene were paired with mice expressing Cre-recombinase under control of the D1 promoter to conditionally knock out expression of TrkB receptors from D1-neurons. RESULTS: Deletion of TrkB receptors from D1 neurons results in obesity in chow fed mice due to increased feed efficiency. In contrast, loss of Trk B signaling in D1 neurons induced hyperphagia and hyperglycemia in mice maintained on high fat diet. CONCLUSIONS: These findings indicate TrkB signaling in D1 neurons regulates body weight by distinct mechanisms for chow and high fat diet and may be important for defending the body against the development of obesity and obesity-related disorders.
OBJECTIVE: Loss of BDNF-TrkB signaling results in obesity in both humans and mice; however, the neural circuit that mediates this effect is unknown. The role of TrkB signaling in dopamine-1 receptor expressing neurons in body weight regulation was tested. METHODS:Mice with a floxed allele of the TrkB gene were paired with mice expressing Cre-recombinase under control of the D1 promoter to conditionally knock out expression of TrkB receptors from D1-neurons. RESULTS: Deletion of TrkB receptors from D1 neurons results in obesity in chow fed mice due to increased feed efficiency. In contrast, loss of Trk B signaling in D1 neurons induced hyperphagia and hyperglycemia in mice maintained on high fat diet. CONCLUSIONS: These findings indicate TrkB signaling in D1 neurons regulates body weight by distinct mechanisms for chow and high fat diet and may be important for defending the body against the development of obesity and obesity-related disorders.
Authors: R T Fremeau; G E Duncan; M G Fornaretto; A Dearry; J A Gingrich; G R Breese; M G Caron Journal: Proc Natl Acad Sci U S A Date: 1991-05-01 Impact factor: 11.205
Authors: Baoji Xu; Evan H Goulding; Keling Zang; David Cepoi; Roger D Cone; Kevin R Jones; Laurence H Tecott; Louis F Reichardt Journal: Nat Neurosci Date: 2003-07 Impact factor: 24.884
Authors: Mary Kay Lobo; Herbert E Covington; Dipesh Chaudhury; Allyson K Friedman; HaoSheng Sun; Diane Damez-Werno; David M Dietz; Samir Zaman; Ja Wook Koo; Pamela J Kennedy; Ezekiell Mouzon; Murtaza Mogri; Rachael L Neve; Karl Deisseroth; Ming-Hu Han; Eric J Nestler Journal: Science Date: 2010-10-15 Impact factor: 47.728
Authors: Juliette Gray; Giles S H Yeo; James J Cox; Jenny Morton; Anna-Lynne R Adlam; Julia M Keogh; Jack A Yanovski; Areeg El Gharbawy; Joan C Han; Y C Loraine Tung; John R Hodges; F Lucy Raymond; Stephen O'rahilly; I Sadaf Farooqi Journal: Diabetes Date: 2006-12 Impact factor: 9.461
Authors: Thomas F Tropea; Zeeba D Kabir; Gagandeep Kaur; Anjali M Rajadhyaksha; Barry E Kosofsky Journal: Front Psychiatry Date: 2011-12-07 Impact factor: 4.157
Authors: Hao Liu; Yang Sun; Xinxin Zhang; Shiyang Li; Dong Hu; Lei Xiao; Yanghui Chen; Lin He; Dao Wen Wang Journal: Front Psychiatry Date: 2020-04-17 Impact factor: 4.157