CRH PVH DMH CCK LH α-msh (POMC) VMH ARC NPY AgRP Orexin MCH
Bar = 5 μm Neurosecretory protein GL (NPGL) 1. vs BBRC (214) 2. 1 3. 4. M C SP NPGL 8aa C GLGKR ( ) C Cys 2 NPGL mrna/actb mrna 8 7 6 5 4 3 2 1 GCE (217) MM IN
NPGL Gen. Comp. Endocrinol. (218 review).1 Human Rat, Mouse Chicken Western painted turtle Western clawed frog Coelacanth Spotted gar Fugu Medaka Elephant shark Lamprey Human MADPGNRGGIHRPLSFTCSLLIVGMCCVSPFFCHSQT--DLLALSQADPQCWESSSVLLL Rat MTDPGTRSRNHCPLSLTCLLLIVGMYYVSPVFCHSQT--DLLTLNQADPQCWESSSMLLL Mouse MADPGPRSRIHSSLSLACSLFIVGICYVSPVFCHSQT--DLLTLNQADPQCWESSSMLLL Chicken M-DFGNRGRIHYNMRLTYSLLVMGVFCVTPSLCHSQI--DPLALGRADPQCWESSSAVLL Western painted turtle M-DPGNRGRIHS-VRLICSLLIMGVFCVTPFFCHSQN--DPLALGRADPQCWEFSTAALL Western clawed frog M-SSRNKRREYYSMQLTCSLLFLGIFVIPAICCHGQV--DPLALGRADPQCWETSTAILL Takifugu M-APSLR------CLPAAMVLLLGCTCVSSLRDHKQVRVDPLSVPQANPHCWKSSSALLL Human EMWKPRVSNTVSGFWDFMIYLKSSENLKHGALFWDLAQLFWDIYVDCVLSRNHGLGRRQL Rat EMRKPRVSNTVSGFWDFMIYLKSSENLKHGALFWDLAQLFWDIYVDCVLSRNHGLGRREL Mouse EMRKPRVSNTVSGFWDFMIYLKSSENLKHGALFWDLAQLFWDIYVDCVLSRNHGLGRREL Chicken EMRKPRISDSVSGFWDFMIFLKSSENLKHGALFWDLAQLFWDIYVDCVLSRTHGLGKRQL Western painted turtle EMRKPRISDSVSGFWDFMIFLKSSENLKHGALFWDLAQLFWDIYVDCVLSRTHGLGRRQL Western clawed frog EMKKPRIADTVSGFWDLMIYLKSSENLKHGILFWDLAQLFWDIYVDCVLSRTHGLGRRQL Takifugu EMRVPRIADTVPAFWDLMVSLRSSDNSKHTALFWDLAQVFWDLYLDCVLSRSHGLGRRHV Human VGEEEKISAAQPQHTRSKQGTYSQLLRTSFLKKKELIEDLISMHVRRSGSSVIGKVN--L Rat AGEEQRVSKVLPRHLGIKQGAYSQLLRSIYLKKKELIGDLTSMQLQKWGPGFTGKEK--L Mouse TGEEEKVSKVLTRHSGIKQGAYSQLLRTLFLKKKELIEDLTSMQMQKRGSRFTGKKK--L Chicken AKAQQRITTLPSQFTGRNQGMFTHIQRSPVLTKKDFFEDLIKNHKHKSRSTLLGRITGEL Western painted turtle AEAEQKITALHSQLTEQKQGTFSHNQRTRVLNKKELIEDLS-IHVHKSGSALLRRVIGGL Western clawed frog NDGNKEITNLISHLTLK---TYSHGQRSILPQKKSLIEELIGIRVHKSESRLLGSIQR-- Takifugu TALHSLFTDSKSFKLPL------------------------------------------- Human EIKRK-- 181 Rat QIKRNRS 183 Mouse EVKRK-- 181 Chicken GKKRK-- 182 Western painted turtle GIKRKQ- 181 Western clawed frog GIKRK-- 177 Takifugu ------- 13
217 4 28 ScienceDaily EurekAlert! AlphaGalileo ScienceNewsline 2
NPGL ISH Endocrinology (217) Control IHC Control Bars = 1 μm
NPGL Rostral A B POMC neurons C B C Endocrinology (217) POMC NPGL DMH POMC NPGL VMH Arc D A D NPY/AgRP neurons E E Rostral Caudal NPY/AgRP NPGL Bars = 1 μm (A, D), 1 μm (B, C, E) POMC neurons NPGL neurons
NPGL Cumulative food intake (g) 4 3 2 1 P=.53 1 2 4 6 8 1 24 Time after injection (h) Endocrinology (217) n = 8,1 P<.5 P<.1 P<.5
NPGL NPGL SP NPGL 8aa GLGRR elife (217) Arcuate nucleus C C NH 2 Mediobasal hypothalamus (MBH) Relative mrna 12 1 8 6 4 2 1: NPGL 6 2: Relative mrna 4 2
NPGL Te VTM f PMD PMV ArcLP ArcMP Cell bodies elife (217) DMH LH VMH Arc Fibers ISH DMH IHC VMH Bars = 1 μm
NPGL Cumulative caloric intake (kcal) 5 4 3 2 1 AAV-CTL AAV-NPGL Body mass (g) 65 55 45 35 25 AAV-CTL AAV-NPGL elife (217) +7 +14 +21 +28 +35 +42 Days after surgery +7 +14 +21 +28 +35 +42 Days after surgery WAT mass/ Body mass (%) 6 4 2 AAV-CTL AAV-NPGL AAV-CTL AAV-NPGL Bars = 5 cm n=6-7, P<.5, P<.1, P<.5
NPGL elife (217) mrna Relative mrna 15 1 5 rwat AAV-CTL 15 AAV-NPGL 1 5 Liver AAV-CTL AAV-NPGL FAS α-tubulin AAV-CTL AAV-NPGL phsl Total HSL Relative Intensity 2 1 FAS 4 3 2 1 phsl/hsl 16:1/16:.5.4.3.2.1 18:1/18: 25 2 15 1 5 n=6-7, P<.5
NPGL elife (217) Calorie intake (kcal) 2 15 1 5 Light CTL NPGL 8 6 4 2 Dark 12 1 8 6 4 2 24 hr 1 3 n = 8, P<.5, P<.5
NPGL elife (217) Npgl mrna (STZ) 2.5 2 1.5 1.5 1.2 1.8.6.4.2 Vehicle NPGL Insulin NPGL pakt Bars = 1 μm n = 7-8, P<.5, P<.1
elife (217)
NPGL
vs
NPGL NPGM chicken NPGM MEFMWKR-R-WYLQ-LGCVLILNLVYA------NLDYLKEAPASLGQIDHQCWEVSSHGLVE 53 chicken NPGL MDFGN-RGRIHYNMRLTYSL---LVMGVFCVTPSLCHSQIDPLALGRADPQCWESSSAVLLE 58 chicken NPGM MKKLKVADPVIALWDFMLFLKESPKPKHNELFNDLAQNFWDMYVDCVLSRSHGMGRRQLVSP 115 chicken NPGL MRKPRISDSVSGFWDFMIFLKSSENLKHGALFWDLAQLFWDIYVDCVLSRTHGLGKRQLAKA 12 Sci. Rep. (218) chicken NPGM RYSSTYSHRTLQGSAFTNPF 135 chicken NPGL QQRITTLPSQFTGRNQGMFTHIQRSPVLTKKDFFEDLIKNHKHKSRSTLLGRITGELGKKRK 182
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H29 D3 M2 M1 B3 B3 B3 A, B,, Lance Kriegsfeld UC Berkeley George Bentley UC Berkeley