title: Photoperiodic and Diurnal Regulation of WNT Signaling in the Arcuate Nucleus of the Female Djungarian Hamster, Phodopus sungorus.
abstract: The WNT pathway was shown to play an important role in the adult central nervous system. We previously identified the WNT pathway as a novel integration site of the adipokine leptin in mediating its neuroendocrine control of metabolism in obese mice. Here we investigated the implication of WNT signaling in seasonal body weight regulation exhibited by the Djungarian hamster (Phodopus sungorus), a seasonal mammal that exhibits profound annual changes in leptin sensitivity. We furthermore investigated whether crucial components of the WNT pathway are regulated in a diurnal manner. Gene expression of key components of the WNT pathway in the hypothalamus of hamsters acclimated to either long day (LD) or short day (SD) photoperiod was analyzed by in situ hybridization. We detected elevated expression of the genes WNT-4, Axin-2, Cyclin-D1, and SFRP-2, in the hypothalamic arcuate nucleus, a key energy balance integration site, during LD compared with SD as well as a diurnal regulation of Axin-2, Cyclin-D1, and DKK-3. Investigating the effect of photoperiod as well as leptin on the activation (phosphorylation) of the WNT coreceptor LRP-6-(Ser1490) by immunohistochemistry, we found elevated activity in the arcuate nucleus during LD relative to SD as well as after leptin treatment (2 mg/kg body weight). These findings indicate that differential WNT signaling may be associated with seasonal body weight regulation and is partially regulated in a diurnal manner in the adult brain. Furthermore, they suggest that this pathway plays a key role in the neuroendocrine regulation of body weight and integration of the leptin signal.
authors.affiliation: Department of Physiology (A.B., A.T.), Centre for Neuroendocrinology and Brain Health Research Centre, University of Otago, Dunedin 9054, New Zealand; Department of Animal Physiology (A.B., J.B., C.H., S.S., A.T.), Faculty of Biology, Philipps University of Marburg, D-35032 Marburg, Germany; and Rowett Institute of Nutrition and Health (G.H.), University of Aberdeen, Aberdeen AB21 9SB, Scotland, United Kingdom.
authors.forename: Alisa
authors.initials: A
authors.lastname: Boucsein
authors.affiliation: Department of Physiology (A.B., A.T.), Centre for Neuroendocrinology and Brain Health Research Centre, University of Otago, Dunedin 9054, New Zealand; Department of Animal Physiology (A.B., J.B., C.H., S.S., A.T.), Faculty of Biology, Philipps University of Marburg, D-35032 Marburg, Germany; and Rowett Institute of Nutrition and Health (G.H.), University of Aberdeen, Aberdeen AB21 9SB, Scotland, United Kingdom.
authors.forename: Jonas
authors.initials: J
authors.lastname: Benzler
authors.affiliation: Department of Physiology (A.B., A.T.), Centre for Neuroendocrinology and Brain Health Research Centre, University of Otago, Dunedin 9054, New Zealand; Department of Animal Physiology (A.B., J.B., C.H., S.S., A.T.), Faculty of Biology, Philipps University of Marburg, D-35032 Marburg, Germany; and Rowett Institute of Nutrition and Health (G.H.), University of Aberdeen, Aberdeen AB21 9SB, Scotland, United Kingdom.
authors.forename: Cindy
authors.initials: C
authors.lastname: Hempp
authors.affiliation: Department of Physiology (A.B., A.T.), Centre for Neuroendocrinology and Brain Health Research Centre, University of Otago, Dunedin 9054, New Zealand; Department of Animal Physiology (A.B., J.B., C.H., S.S., A.T.), Faculty of Biology, Philipps University of Marburg, D-35032 Marburg, Germany; and Rowett Institute of Nutrition and Health (G.H.), University of Aberdeen, Aberdeen AB21 9SB, Scotland, United Kingdom.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Stöhr
authors.affiliation: Department of Physiology (A.B., A.T.), Centre for Neuroendocrinology and Brain Health Research Centre, University of Otago, Dunedin 9054, New Zealand; Department of Animal Physiology (A.B., J.B., C.H., S.S., A.T.), Faculty of Biology, Philipps University of Marburg, D-35032 Marburg, Germany; and Rowett Institute of Nutrition and Health (G.H.), University of Aberdeen, Aberdeen AB21 9SB, Scotland, United Kingdom.
authors.forename: Gisela
authors.initials: G
authors.lastname: Helfer
authors.affiliation: Department of Physiology (A.B., A.T.), Centre for Neuroendocrinology and Brain Health Research Centre, University of Otago, Dunedin 9054, New Zealand; Department of Animal Physiology (A.B., J.B., C.H., S.S., A.T.), Faculty of Biology, Philipps University of Marburg, D-35032 Marburg, Germany; and Rowett Institute of Nutrition and Health (G.H.), University of Aberdeen, Aberdeen AB21 9SB, Scotland, United Kingdom.
authors.forename: Alexander
authors.initials: A
authors.lastname: Tups
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D060466:Axin Protein / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects / Q000235:genetics*; D002940:Circadian Rhythm / Q000187:drug effects / Q000235:genetics*; D006224:Cricetinae; D019938:Cyclin D1 / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D020738:Leptin / Q000494:pharmacology; D008565:Membrane Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D017111:Phodopus; D017440:Photoperiod; D012621:Seasons; D060449:Wnt Signaling Pathway / Q000187:drug effects / Q000235:genetics*; D060528:Wnt4 Protein / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism
chemical_list: D060466:Axin Protein; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D008565:Membrane Proteins; D060528:Wnt4 Protein; D019938:Cyclin D1