title: Ablation of LMO4 in glutamatergic neurons impairs leptin control of fat metabolism.
abstract: The LIM domain only 4 (LMO4) protein is expressed in the hypothalamus, but its function there is not known. Using mice with LMO4 ablated in postnatal glutamatergic neurons, including most neurons of the paraventricular (PVN) and ventromedial (VMH) hypothalamic nuclei where LMO4 is expressed, we asked whether LMO4 is required for metabolic homeostasis. LMO4 mutant mice exhibited early onset adiposity. These mice had reduced energy expenditure and impaired thermogenesis together with reduced sympathetic outflow to adipose tissues. The peptide hormone leptin, produced from adipocytes, activates Jak/Stat3 signaling at the hypothalamus to control food intake, energy expenditure, and fat metabolism. Intracerebroventricular infusion of leptin suppressed feeding similarly in LMO4 mutant and control mice. However, leptin-induced fat loss was impaired and activation of Stat3 in the VMH was blunted in these mice. Thus, our study identifies LMO4 as a novel modulator of leptin function in selective hypothalamic nuclei to regulate fat metabolism.
authors.affiliation: Centre for Stroke Recovery, Neuroscience, Ottawa Health Research Institute, University of Ottawa, 451 Smyth Road, Ottawa, ON K1H 8M5, Canada.
authors.forename: Xun
authors.initials: X
authors.lastname: Zhou
authors.forename: Mariana
authors.initials: M
authors.lastname: Gomez-Smith
authors.forename: Zhaohong
authors.initials: Z
authors.lastname: Qin
authors.forename: Philippe M
authors.initials: PM
authors.lastname: Duquette
authors.forename: Arturo
authors.initials: A
authors.lastname: Cardenas-Blanco
authors.forename: Punarpreet S
authors.initials: PS
authors.lastname: Rai
authors.forename: Mary-Ellen
authors.initials: ME
authors.lastname: Harper
authors.forename: Eve C
authors.initials: EC
authors.lastname: Tsai
authors.forename: Hymie
authors.initials: H
authors.lastname: Anisman
authors.forename: Hsiao-Huei
authors.initials: HH
authors.lastname: Chen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D004734:Energy Metabolism; D053612:Janus Kinases / Q000378:metabolism; D060588:LIM Domain Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020738:Leptin / Q000378:metabolism*; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D014697:Ventromedial Hypothalamic Nucleus / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D060588:LIM Domain Proteins; D020738:Leptin; C491976:Lmo4 protein, mouse; D050796:STAT3 Transcription Factor; D053612:Janus Kinases