title: Overexpression of suppressor of cytokine signaling 3 in the arcuate nucleus of juvenile Phodopus sungorus alters seasonal body weight changes.
abstract: The profound seasonal cycle in body weight exhibited by the Djungarian hamster (Phodopus sungorus) is associated with the development of hypothalamic leptin resistance during long day photoperiod (LD, 16:8 h light dark cycle), when body weight is elevated relative to short day photoperiod (SD, 8:16 h light dark cycle). We previously have shown that this seasonal change in physiology is associated with higher levels of mRNA for the potent inhibitor of leptin signaling, suppressor of cytokine signaling-3 (SOCS3), in the arcuate nucleus (ARC) of LD hamsters relative to hamsters in SD. The alteration in SOCS3 gene expression preceded the body weight change suggesting that SOCS3 might be the molecular switch of seasonal body weight changes. To functionally characterize the role of SOCS3 in seasonal body weight regulation, we injected SOCS3 expressing recombinant adeno-associated virus type-2 (rAAV2-SOCS3) constructs into the ARC of leptin sensitive SD hamsters immediately after weaning. Hamsters that received rAAV2 expressing enhanced green fluorescent protein (rAAV2-EGFP) served as controls. ARC-directed SOCS3 overexpression led to a significant increase in body weight over a period of 12 weeks without fully restoring the LD phenotype. This increase was partially due to elevated brown and white adipose tissue mass. Gene expression of pro-opiomelanocortin was increased while thyroid hormone converting enzyme DIO3 mRNA levels were reduced in SD hamsters with SOCS3 overexpression. In conclusion, our data suggest that ARC-directed SOCS3 overexpression partially overcomes the profound seasonal body weight cycle exhibited by the hamster which is associated with altered pro-opiomelanocortin and DIO3 gene expression.
authors.affiliation: Department of Animal Physiology, Faculty of Biology, Philipps University Marburg, Karl-von-Frisch Str. 8, 35043, Marburg, Germany, ganjam@staff.uni-marburg.de.
authors.forename: Goutham K
authors.initials: GK
authors.lastname: Ganjam
authors.forename: Jonas
authors.initials: J
authors.lastname: Benzler
authors.forename: Olaf
authors.initials: O
authors.lastname: Pinkenburg
authors.forename: Alisa
authors.initials: A
authors.lastname: Boucsein
authors.forename: Sigrid
authors.initials: S
authors.lastname: Stöhr
authors.forename: Juliane
authors.initials: J
authors.lastname: Steger
authors.forename: Carsten
authors.initials: C
authors.lastname: Culmsee
authors.forename: Perry
authors.initials: P
authors.lastname: Barrett
authors.forename: Alexander
authors.initials: A
authors.lastname: Tups
mesh_terms: D000273:Adipose Tissue / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism*; D001835:Body Weight / Q000502:physiology*; D003001:Cloning, Molecular; D006224:Cricetinae; D017931:DNA Primers / Q000235:genetics; D000229:Dependovirus; D005786:Gene Expression Regulation / Q000502:physiology*; D005822:Genetic Vectors / Q000008:administration & dosage; D049452:Green Fluorescent Proteins / Q000378:metabolism; D017403:In Situ Hybridization; D017111:Phodopus / Q000378:metabolism*; D017440:Photoperiod; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D012621:Seasons; D050826:Suppressor of Cytokine Signaling Proteins / Q000008:administration & dosage / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D050826:Suppressor of Cytokine Signaling Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D011333:Pro-Opiomelanocortin