title: Identification of a Peptidergic Pathway Critical to Satiety Responses in Drosophila.
abstract: Although several neural pathways have been implicated in feeding behaviors in mammals [1-7], it remains unclear how the brain coordinates feeding motivations to maintain a constant body weight (BW). Here, we identified a neuropeptide pathway important for the satiety and BW control in Drosophila. Silencing of myoinhibitory peptide (MIP) neurons significantly increased BW through augmented food intake and fat storage. Likewise, the loss-of-function mutation of mip also increased feeding and BW. Suppressing the MIP pathway induced satiated flies to behave like starved ones, with elevated sensitivity toward food. Conversely, activating MIP neurons greatly decreased food intake and BW and markedly blunted the sensitivity of starved flies toward food. Upon terminating the activation protocol of MIP neurons, the decreased BW reverts rapidly to the normal level through a strong feeding rebound, indicating the switch-like role of MIP pathway in feeding. Surprisingly, the MIP-mediated BW decrease occurred independently of sex peptide receptor (SPR), the only known receptor for MIP, suggesting the presence of a yet-unknown MIP receptor. Together, our results reveal a novel anorexigenic pathway that controls satiety in Drosophila and provide a new avenue to study how the brain actively maintains a constant BW.
authors.affiliation: National Creative Research Initiatives Center for Energy Homeostasis Regulation, Institute of Molecular Biology and Genetics and School of Biological Sciences, Seoul National University, 599 Gwanak-Ro, Gwanak-Gu, Seoul 151-742, Republic of Korea.
authors.forename: Soohong
authors.initials: S
authors.lastname: Min
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
authors.forename: Hyo-Seok
authors.initials: HS
authors.lastname: Chae
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
authors.forename: Yong-Hoon
authors.initials: YH
authors.lastname: Jang
authors.affiliation: National Creative Research Initiatives Center for Energy Homeostasis Regulation, Institute of Molecular Biology and Genetics and School of Biological Sciences, Seoul National University, 599 Gwanak-Ro, Gwanak-Gu, Seoul 151-742, Republic of Korea.
authors.forename: Sekyu
authors.initials: S
authors.lastname: Choi
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Republic of Korea.
authors.forename: Sion
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Oral Biology, Yonsei University College of Dentistry, Seoul 120-752, Republic of Korea.
authors.forename: Yong Taek
authors.initials: YT
authors.lastname: Jeong
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Republic of Korea.
authors.forename: Walton D
authors.initials: WD
authors.lastname: Jones
authors.affiliation: Department of Oral Biology, Yonsei University College of Dentistry, Seoul 120-752, Republic of Korea.
authors.forename: Seok Jun
authors.initials: SJ
authors.lastname: Moon
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea. Electronic address: kimyj@gist.ac.kr.
authors.forename: Young-Joon
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: National Creative Research Initiatives Center for Energy Homeostasis Regulation, Institute of Molecular Biology and Genetics and School of Biological Sciences, Seoul National University, 599 Gwanak-Ro, Gwanak-Gu, Seoul 151-742, Republic of Korea. Electronic address: jkc@snu.ac.kr.
authors.forename: Jongkyeong
authors.initials: J
authors.lastname: Chung
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001835:Body Weight; D001921:Brain / Q000502:physiology; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004435:Eating; D005247:Feeding Behavior; D005260:Female; D005786:Gene Expression Regulation; D007473:Ion Channels; D008297:Male; D009474:Neurons / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D018000:Receptors, Peptide; D012528:Satiety Response / Q000502:physiology*; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D007473:Ion Channels; D010455:Peptides; D018000:Receptors, Peptide; D000074025:TRPA1 Cation Channel; D050052:TRPC Cation Channels; C475684:TrpA1 protein, Drosophila; C000603492:myoinhibitory peptide, Drosophila; C526291:sex peptide receptor, Drosophila