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 ......................