title: Deficiency of PTP1B in POMC neurons leads to alterations in energy balance and homeostatic response to cold exposure.
abstract: The adipose tissue-derived hormone leptin regulates energy balance through catabolic effects on central circuits, including proopiomelanocortin (POMC) neurons. Leptin activation of POMC neurons increases thermogenesis and locomotor activity. Protein tyrosine phosphatase 1B (PTP1B) is an important negative regulator of leptin signaling. POMC neuron-specific deletion of PTP1B in mice results in reduced high-fat diet-induced body weight and adiposity gain due to increased energy expenditure and greater leptin sensitivity. Mice lacking the leptin gene (ob/ob mice) are hypothermic and cold intolerant, whereas leptin delivery to ob/ob mice induces thermogenesis via increased sympathetic activity to brown adipose tissue (BAT). Here, we examined whether POMC PTP1B mediates the thermoregulatory response of CNS leptin signaling by evaluating food intake, body weight, core temperature (T(C)), and spontaneous physical activity (SPA) in response to either exogenous leptin or 4-day cold exposure (4°C) in male POMC-Ptp1b-deficient mice compared with wild-type controls. POMC-Ptp1b(-/-) mice were hypersensitive to leptin-induced food intake and body weight suppression compared with wild types, yet they displayed similar leptin-induced increases in T(C). Interestingly, POMC-Ptp1b(-/-) mice had increased BAT weight and elevated plasma triiodothyronine (T(3)) levels in response to a 4-day cold challenge, as well as reduced SPA 24 h after cold exposure, relative to controls. These data show that PTP1B in POMC neurons plays a role in short-term cold-induced reduction of SPA and may influence cold-induced thermogenesis via enhanced activation of the thyroid axis.
authors.affiliation: Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Bart C
authors.initials: BC
authors.lastname: De Jonghe
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Hayes
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Banno
authors.forename: Karolina P
authors.initials: KP
authors.lastname: Skibicka
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Zimmer
authors.forename: Kerisha A
authors.initials: KA
authors.lastname: Bowen
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Leichner
authors.forename: Amber L
authors.initials: AL
authors.lastname: Alhadeff
authors.forename: Scott E
authors.initials: SE
authors.lastname: Kanoski
authors.forename: Nicole E
authors.initials: NE
authors.lastname: Cyr
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Nillni
authors.forename: Harvey J
authors.initials: HJ
authors.lastname: Grill
authors.forename: Kendra K
authors.initials: KK
authors.lastname: Bence
mesh_terms: D000818:Animals; D003080:Cold Temperature; D004734:Energy Metabolism / Q000235:genetics* / Q000502:physiology*; D054439:Ghrelin / Q000097:blood; D006706:Homeostasis / Q000235:genetics* / Q000502:physiology*; D007031:Hypothalamus / Q000378:metabolism; D008027:Light; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D011333:Pro-Opiomelanocortin / Q000502:physiology*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012313:RNA / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D054440:Receptors, Ghrelin / Q000096:biosynthesis; D015398:Signal Transduction / Q000502:physiology; D013686:Telemetry; D022722:Thermogenesis / Q000502:physiology; D013963:Thyroid Hormones / Q000097:blood; D013972:Thyrotropin / Q000378:metabolism
chemical_list: D054439:Ghrelin; D012333:RNA, Messenger; D054440:Receptors, Ghrelin; D013963:Thyroid Hormones; D012313:RNA; D011333:Pro-Opiomelanocortin; D013972:Thyrotropin; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C516609:Ptpn1 protein, mouse