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UNIVERZITA KARLOVA V PRAZE
Prodovdeck fakulta
Katedra fyziologie ivoich
BAKALSK PRCE
NEUROPEPTID Y A REGULACE PJMU POTRAVY NEUROPEPTIDE Y AND FOOD INTAKE REGULATION
Barbora Vchov
kolitel: RNDr. Jara Nedvdkov, CSc.
Praha 2010
Prohlauji, e jsem bakalskou prci Neuropeptid Y a regulace pjmu potravy vypracovala
samostatn s pouitm uveden literatury a na zklad konzultac se svou kolitelkou.
V Praze dne ..............................
........................................................
Dkuji sv kolitelce RNDr. Jae Nedvkov, CSc. za cenn rady, pipomnky a trplivost. Zrove
bych chtla podkovat i panu Doc. RNDr. Stanislavu Vybralovi, CSc. za as, kter mi vdy ochotn
vnoval.
1
ABSTRAKT
Neuropeptid Y (NPY) je sloen ze 36 aminokyselin a je soust NPY rodiny. Jeho biosyntza probh
v hypothalamu a roku 2007 byla popsna jeho exprese i v tukov tkni. NPY je vudyptomn
hormon s centrln i perifern aktivitou, kter celkov vede k udren homeostzy. Je tak jednm
z nejvznamnjch orexigennch hormon. Pro sv inky na regulaci pjmu potravy vyuv
receptory spaen s G-proteiny typu Y1, Y2 a Y5; vzhledem k mnoha zvanm vedlejm inkm
souasnch lk na snen hmotnosti jsou ligandy tchto receptor (antagonist Y1R a Y5R, agonist
Y2R) nyn uvaovny jako nov lebn ltky proti obezit.
Tato prce je zamena na obecnou charakteristiku NPY jako orexigennho faktoru a monosti vyuit
ltek od nj odvozench pro lbu obezity.
Klov slova: Neuropepid Y (NPY), hypothalamus, pjem potravy, obezita, receptory pro NPY, lky
proti obezit
ABSTRACT
Neuropeptide Y (NPY) is a 36-amino acid member of NPY family. Its biosynthesis occurs in the
hypothalamus and its expression also in adipose tissue was described in 2007. NPY is an ubiquitous
hormone with central and peripheral effects which lead to the maintenance of homeostasis; NPY is
also one of the most significant orexigenic hormones. NPY utilizes G-protein coupled receptors Y1,
Y2 and Y5 for its food intake regulation; owing to serious side effects of currently used anti-obesity
drugs, the ligands of these receptors (Y1R and Y5R antagonists and Y2R agonists) are considered as
targeting molecules for a new therapeutic strategy for obesity treatment.
This work is focused on the characteristic of NPY as an orexigenic agent and the possibility of using
NPY-based drugs for obesity treatment.
Keywords: Neuropeptide Y (NPY), hypothalamus, food intake, obesity, NPY receptors, anti-obesity
drugs
2
SEZNAM POUITCH ZKRATEK
AAV adeno-associated virus
ACTH adrenocorticotropic hormone adrenokortikotropn hormon
AEA ananamide ananamid
AK aminokyselina
ARC nucleus arcuatus
BMI body mass index index tlesn hmotnosti
CNS centrln nervov soustava
CORT corticosterone kortikosteron
cRNA complementary RNA komplementrn RNA
DIO diet-induced obesity obezita vyvolan stravovacmi
nvyky
DMN dorsomedial nucleus dorzomediln jdro
DR diet-resistant
fa gen fatty gene
GABA -aminobutyric acid kyseliny -amino mseln
GHS-R growth hormone secretagogue receptor pro sekreci
receptor rstovch hormon
HC a high-carbohydrate diet strava bohat na sacharidy
HF a high-fat diet strava bohat na tuky
ICV intracerebroventricular intracerebroventrikulrn
IHC an intermediate-carbohydrate strava se stednm obsahem
diet sacharid
IHF an intramediate-fat diet strava se stednm obsahem
tuk
LF low-fat diet strava s nzkm obsahem tuk
LH lateral hypothalamus laterln hypothalamus
LPL lipoprotein lipase lipoproteinov lipza
MC4-R melanocortin-4 receptor melanokortinov receptor 4
MSH melanocytes-stimulating melanocyty stimulujc
hormone hormon
NA noradrenaline noradrenalin
NGF nerve growth factor nervov rstov faktor
3
NPY neuropeptide Y (neuropeptide neuropeptid Y (neuropeptid
tyrosine) tyrozin)
nt nukleotide nukleotid
ob gen obese gene
PAM peptidyl-aminotransferase peptidyl-aminotransferza
PP pancreatic polypeptide pankreatick polypeptid
PY pancreatic peptide Y pankreatick peptid Y
PYY peptide YY peptid YY
PYY(3-36) peptide YY (3-36) peptid YY (3-36)
PYY4 peptide YY 4 peptid YY 4
PVN paraventricular nucleus paraventrikulrn jdro
rh NPY recombinant human NPY lidsk rekombinantn NPY
TNF- tumor necrosis factor faktor zpsobujc nekrzu
ndor
UTR untranslated region nepekldan oblast
Y1R Y1 receptor Y1 receptor
Y2R Y2 receptor Y2 receptor
Y3R Y3 receptor Y3 receptor
Y4R Y4 receptor Y4 receptor
Y5R Y5 receptor Y5 receptor
VMH ventromedial hypothalamus ventromediln hypothalamus
VMN ventromedial nucleus ventromediln jdro
7TM 7 transmembrane receptor 7-transmembrnov
receptor (serpetnov)
4
OBSAH
Abstrakt ................................................................................................................................................... 1
Seznam pouitch zkratek ....................................................................................................................... 2
Obsah ....................................................................................................................................................... 4
1. vod .................................................................................................................................................... 6
2. Neuropeptidy ....................................................................................................................................... 8
2.1.Objev neuropeptid ....................................................................................................................... 8
2.2. Biosyntza a uvolovn neuropeptid ......................................................................................... 8
2.3. Rodiny gen pro neuropeptidy ................................................................................................... 10
2.4. Funkce neuropeptid .................................................................................................................. 11
3. Neuropeptid Y ................................................................................................................................... 12
3.1. NPY rodina ................................................................................................................................. 12
3.1.1. Receptory pro rodinu NPY .................................................................................................. 12
3.2. Struktura NPY ............................................................................................................................ 14
3.3. Genov exprese NPY .................................................................................................................. 15
3.4. Metabolismus NPY ..................................................................................................................... 16
3.4.1. Biosyntza NPY ................................................................................................................... 16
3.4.2. Degradace NPY ................................................................................................................... 16
3.5. NPY jako regultor pjmu potravy ............................................................................................ 17
3.5.1. Orexigenn inek NPY ....................................................................................................... 18
3.5.2. Vztah exprese NPY k pjmu potravy a tlesn hmotnosti .................................................. 18
3.5.3. Lokalizace mst hypothalamu zastnnch v inku NPY na pjem potravy ................... 19
3.5.4. NPY a motivace k pjmu potravy ....................................................................................... 19
3.5.5. NPY a typ nutrient v potrav ............................................................................................. 19
3.5.6 Orexigenn receptory pro NPY ............................................................................................. 19
3.5.7. Anorexigenn Y-receptory ................................................................................................... 20
3.6. Faktory ovlivujc endogenn NPY ........................................................................................... 20
5
3.6.1. Hladovn ............................................................................................................................. 20
3.6.2. Cirkadinn ovlivnn .......................................................................................................... 20
3.6.3. Sloen stravy ....................................................................................................................... 21
3.6.4. Glukza ................................................................................................................................ 22
3.6.5. Inzulin ......................