Leptin

Leptin
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	1AX8
Identifikatori
Aliasi	LEP
Vanjski ID-jevi	OMIM: 164160 MGI: 104663 HomoloGene: 193 GeneCards: LEP
Lokacija gena (čovjek)
Hrom.	Hromosom 7 (čovjek)
Kraj	128,257,629 bp
Lokacija gena (miš)
Hrom.	Hromosom 6 (miš)
Kraj	29,073,876 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• hormone activity; • peptide hormone receptor binding; • signaling receptor binding;
Ćelijska komponenta	• citoplazma; • extracellular region; • Vanćelijsko;
Biološki proces	• regulation of protein phosphorylation; • response to dietary excess; • cellular response to retinoic acid; • positive regulation of developmental growth; • negative regulation of glucagon secretion; • Placentacija; • cardiac muscle hypertrophy; • regulation of angiogenesis; • prostaglandin secretion; • regulation of intestinal cholesterol absorption; • T cell differentiation; • positive regulation of reactive oxygen species metabolic process; • central nervous system neuron development; • Jednodnevni biološki ritam; • positive regulation of ion transport; • Angiogeneza; • glucose metabolic process; • positive regulation of peroxisome proliferator activated receptor signaling pathway; • positive regulation of hepatic stellate cell activation; • regulation of endothelial cell proliferation; • intestinal absorption; • response to ethanol; • negative regulation of autophagy; • positive regulation of p38MAPK cascade; • positive regulation of protein kinase B signaling; • negative regulation of metabolic process; • negative regulation of vasoconstriction; • glucose homeostasis; • regulation of insulin secretion; • regulation of steroid biosynthetic process; • insulin secretion; • regulation of natural killer cell activation; • regulation of fat cell differentiation; • response to vitamin E; • response to nutrient levels; • bone mineralization involved in bone maturation; • positive regulation of T cell proliferation; • positive regulation of protein import into nucleus; • regulation of brown fat cell differentiation; • fatty acid beta-oxidation; • regulation of metabolic process; • hormone metabolic process; • positive regulation of MAPK cascade; • positive regulation of TOR signaling; • cellular response to L-ascorbic acid; • ovulation from ovarian follicle; • activation of protein kinase C activity; • spolno razmnožavanje; • negative regulation of cartilage development; • response to nutrient; • negative regulation of glutamine transport; • leptin-mediated signaling pathway; • bile acid metabolic process; • female pregnancy; • negative regulation of apoptotic process; • cholesterol metabolic process; • positive regulation of follicle-stimulating hormone secretion; • GO:1901227 negative regulation of transcription by RNA polymerase II; • negative regulation of appetite; • regulation of protein localization to nucleus; • regulation of blood pressure; • negative regulation of glucose import; • leukocyte tethering or rolling; • negative regulation of lipid storage; • adipose tissue development; • GO:1903106 positive regulation of insulin receptor signaling pathway; • bone growth; • positive regulation of receptor signaling pathway via JAK-STAT; • glycerol biosynthetic process; • positive regulation of luteinizing hormone secretion; • fatty acid catabolic process; • regulation of gluconeogenesis; • response to estradiol; • GO:0007243 intracellular signal transduction; • adult feeding behavior; • response to hypoxia; • regulation of natural killer cell proliferation; • eating behavior; • GO:0032737 positive regulation of cytokine production; • regulation of cytokine production involved in inflammatory response; • regulation of nitric-oxide synthase activity; • response to activity; • cellular response to leptin stimulus; • regulation of cell cycle; • regulation of natural killer cell mediated cytotoxicity; • positive regulation of fat cell apoptotic process; • positive regulation of cell population proliferation; • regulation of lipoprotein lipid oxidation; • positive regulation of phosphatidylinositol 3-kinase signaling; • GO:0072468 Transdukcija signala; • regulation of bone remodeling; • lipid metabolism; • negative regulation of appetite by leptin-mediated signaling pathway; • interleukin-12 production; • positive regulation of tumor necrosis factor production; • interleukin-6 production; • response to insulin; • tyrosine phosphorylation of STAT protein; • Fagocitoza; • energy reserve metabolic process; • positive regulation of tyrosine phosphorylation of STAT protein; • regulation of signaling receptor activity; • determination of adult lifespan; • regulation of lipid biosynthetic process; • positive regulation of cold-induced thermogenesis; • aorta development; • GO:0048552 regulation of catalytic activity; • elastin metabolic process;
	Izvori:Amigo / QuickGO
Ortolozi
	3952
	16846
	ENSG00000174697
	ENSMUSG00000059201
	P41159
	P41160
	NM_000230
	NM_008493
	NP_000221
	NP_032519
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Leptin (grč. λεπτός - leptos = tanak) je proteinski hormon sa 16 kDa. Učestvuje u regulaciji unosa i potrošnje energije, putem uvećavanja apetita i metabolizma. To je jedan od najvažnijih hormona adipoznog porijekla.^[5] Gen Ob(Lep) (latinskiobese - gojazan) kod čovjeka je na hromosomu 7.^[6]

Djelovanje uredi

Dva bijela laboratoijska miša, slične veličine ušiju, crnih očiju i ružičastih noseva: lijevi je oko tri puta krupniji od miša normalne veličine, desno. Lijevi je genetički nesposoban za proizvodnju leptina, što uzrokuje gojaznost.

Leptin je odmah nakon otkrića uzročno povezan s gojaznošću pa je pretpostavljeno da bi se njegovom terapijskom primjenom u ljudi mogla liječiti prekomjerna težina. Primjena rekombiniranog leptina u gojaznl+ih osoba međutim doživjela je neuspjeh jer je uticaj leptina na njihovu težinu bio klinički vrlo slab. Otkriveno je tek nekoliko porodica u svijetu s pravim genetičkim nedostatkom leptina, što ih od najranijeg djetinjstva čini ekstremno debelim i samo je kod njih primjena leptina našla svoj izvorni smisao.

Uloga leptina pokazala se, ipak, izrazito složenijom nego što se to u početku činilo. Leptin djeluje kao aferentni signal u jezgrima hipotalamusa u dva smjera: smanjuje aktivnost puteva koji podstiču glad, a stimulira aktivnost putova koji izazivaju sitost. Osim na smanjenje unosa hrane, leptin djeluje i na pojačanu potrošnju energije, utjecajem na simpatički nervni sistem i termogenezu. Prosljeđujući informaciju hipotalamusu o količini energije koja je pohranjena u masnom tkivu, leptin predstavlja dio povratne sprege, koja kontrolira stabilnost ukupnih zaliha energije.Pri gladovanju, nivo leptina opada i neposredno se potiču sveukupni hormonski, metabolički i kognitivni mehanizmi prilagodbe na nedostatak hrane, te dolazi do pojačanja apetita i smanjenja energetske potrošnje. U obrnutom slučaju, pri obilju raspoložive hrane, leptin smanjuje apetit i pojačava energetsku potrošnju. Promjene razine leptina djeluju u pravcu sprečavanja promjene težine u bilo kojem smjeru poput termostata.

Tjelesna težina kao rezultat unosa i potrošnje energije u većine odraslih ljudi godinama vrlo je stabilna. U osoba s normalnom tjelesnom masom, ta homeostaza energije održava se na razini oko 20% masti u tjelesnoj težini, ali u gojaznih osoba ta ravnoteža je pomjerena za više od 30%. Razlog tome je u razvoju leptinske rezistencije: dolazi do smanjene osjetljivosti leptinske povratne sprege i neuspjeha povrata na prethodnu težinu uz porast leptina. Gojazne osobe i imaju dovoljno, zapravo čak povećane količine leptina, ali njihov hipotalamus ne uspijeva dobiti podatak o dovoljnosti količini energetskih zaliha.

Složene olfaktorne, vizualne, emocijske, više kognitivne funkcije, a i nekoliko drugih signalnih puteva utiču na hranjenje, ali već u ovome osnovnom leptinskom mehanizmu povratne sprege krije se patogeneza gojaznosti. U suprotnosti sa svjesnom željom za mršavljenjem, snažni biološki, podsvjesni mehanizmi održavaju tjelesnu težinu stalnom i razlog su neuspjeha većine ljudi u nastojanjima za smanjenjem težine.

Uz upravljanje homeostazom energije - među važnim učincima leptina također je uticaj na neuroendokrine funkcije. Dokazana je uloga leptina u sazrijevanju i aktivaciji reproduktivne osi. Pubertetskom porastu gonadotropina i estradiola, prethodi porast nivoa leptina, odnosno testosterona. Iako nije neposredni okidač za početak puberteta, leptin se smatra permisivnim faktorom ili signalom spremnosti: razina leptina ukazuje na zadovoljavajuću težinu i energetske zalihe koje omogućuju plodnost.

Osim centralnih učinaka leptina, posebno se ističe njegova interakcija sa upalnim sistemom. Leptin se ponajprije smatra proupalnim faktorom, ali istodobno štiti od infekcija.To djelovanje tumači se kao prilagodba za jačanje imunskih sposobnosti, a u suprotnosti je s imunosupresivnim učinkom gladovanja.

Također pogledajte uredi

Reference uredi

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000174697 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000059201 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Brennan AM, Mantzoros CS (2006). "Drug Insight: the role of leptin in human physiology and pathophysiology--emerging clinical applications". Nat Clin Pract Endocrinol Metab. 2 (6): 318–27. doi:10.1038/ncpendmet0196. PMID 16932309.
^ GreGreen ED, Maffei M, Braden VV, Proenca R, DeSilva U, Zhang Y, Chua SC Jr, Leibel RL, Weissenbach J, Friedman JM (1995). "The human obese (OB) gene: RNA expression pattern and mapping on the physical, cytogenetic, and genetic maps of chromosome 7". Genome Res. 5 (1): 5–12. doi:10.1101/gr.5.1.5. PMID 8717050.CS1 održavanje: više imena: authors list (link)

Dopunska literatura uredi

Torday JS, Sun H, Wang L, Torres E, Sunday ME, Rubin LP (2002). "Leptin mediates the parathyroid hormone-related protein paracrine stimulation of fetal lung maturation". Am. J. Physiol. Lung Cell Mol. Physiol. 282 (3): L405–10. PMC 2942763. PMID 11839533.CS1 održavanje: više imena: authors list (link)
Torday JS, Rehan VK (2002). "Stretch-stimulated surfactant synthesis is coordinated by the paracrine actions of PTHrP and leptin". Am. J. Physiol. Lung Cell Mol. Physiol. 283 (1): L130–5. doi:10.1152/ajplung.00380.2001. PMID 12060569.
Dubey L, Hesong Z (2006). "Role of leptin in atherogenesis". Exp Clin Cardiol. 11 (4): 269–75. PMC 2274849. PMID 18651016.
Friedman JM, Halaas JL (1998). "Leptin and the regulation of body weight in mammals". Nature. 395 (6704): 763–70. doi:10.1038/27376. PMID 9796811.
Prolo P, Wong ML, Licinio J (1999). "Leptin". Int. J. Biochem. Cell Biol. 30 (12): 1285–90. doi:10.1016/S1357-2725(98)00094-6. PMID 9924798.CS1 održavanje: više imena: authors list (link)
Heshka JT, Jones PJ (2001). "A role for dietary fat in leptin receptor, OB-Rb, function". Life Sci. 69 (9): 987–1003. doi:10.1016/S0024-3205(01)01201-2. PMID 11508653.
Janeckova R (2002). "The role of leptin in human physiology and pathophysiology". Physiological research / Academia Scientiarum Bohemoslovaca. 50 (5): 443–59. PMID 11702849.
Lee DW, Leinung MC, Rozhavskaya-Arena M, Grasso P (2002). "Leptin and the treatment of obesity: its current status". Eur. J. Pharmacol. 440 (2–3): 129–39. doi:10.1016/S0014-2999(02)01424-3. PMID 12007531.CS1 održavanje: više imena: authors list (link)
Al-Daghri N, Bartlett WA, Jones AF, Kumar S (2002). "Role of leptin in glucose metabolism in type 2 diabetes". Diabetes, obesity & metabolism. 4 (3): 147–55. doi:10.1046/j.1463-1326.2002.00194.x. PMID 12047393.CS1 održavanje: više imena: authors list (link)
Sabath Silva EF (2002). "[Leptin]". Rev. Invest. Clin. 54 (2): 161–5. PMID 12053815.
Thomas T, Burguera B (2003). "Is leptin the link between fat and bone mass?". J. Bone Miner. Res. 17 (9): 1563–9. doi:10.1359/jbmr.2002.17.9.1563. PMID 12211425.
Kraemer RR, Chu H, Castracane VD (2002). "Leptin and exercise". Exp. Biol. Med. (Maywood). 227 (9): 701–8. PMID 12324651.CS1 održavanje: više imena: authors list (link)
Waelput W, Brouckaert P, Broekaert D, Tavernier J (2003). "A role for leptin in the systemic inflammatory response syndrome (SIRS) and in immune response". Current drug targets. Inflammation and allergy. 1 (3): 277–89. doi:10.2174/1568010023344634. PMID 14561193.CS1 održavanje: više imena: authors list (link)
Stenvinkel P, Pecoits-Filho R, Lindholm B (2004). "Leptin, ghrelin, and proinflammatory cytokines: compounds with nutritional impact in chronic kidney disease?". Advances in renal replacement therapy. 10 (4): 332–45. doi:10.1053/j.arrt.2003.08.009. PMID 14681862.CS1 održavanje: više imena: authors list (link)
Cohen P, Ntambi JM, Friedman JM (2004). "Stearoyl-CoA desaturase-1 and the metabolic syndrome". Curr. Drug Targets Immune Endocr. Metabol. Disord. 3 (4): 271–80. doi:10.2174/1568008033340117. PMID 14683458.CS1 održavanje: više imena: authors list (link)
Sahu A (2004). "Leptin signaling in the hypothalamus: emphasis on energy homeostasis and leptin resistance". Frontiers in neuroendocrinology. 24 (4): 225–53. doi:10.1016/j.yfrne.2003.10.001. PMID 14726256.
Elefteriou F, Karsenty G (2004). "[Bone mass regulation by leptin: a hypothalamic control of bone formation]". Pathol. Biol. 52 (3): 148–53. doi:10.1016/j.patbio.2003.05.006. PMID 15063934.
Blüher S, Mantzoros CS (2004). "The role of leptin in regulating neuroendocrine function in humans". J. Nutr. 134 (9): 2469S–2474S. PMID 15333744.
Farooqi S, O'Rahilly S (2007). "Genetics of obesity in humans". Endocr. Rev. 27 (7): 710–18. doi:10.1210/er.2006-0040. PMID 17122358.

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Vanjski linkovi uredi

Leptin Arhivirano 24. 6. 2013. na Wayback Machine
Leptin: Vaš mozak, apetit i gojaznost
Leptin/grelin i njihova uloga u gojaznosti Arhivirano 14. 8. 2013. na Wayback Machine
Leptin Arhivirano 26. 10. 2011. na Wayback Machine
Leptin na 3Dchem.com

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000174697 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000059201 - Ensembl, maj 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid16932309-5] Brennan AM, Mantzoros CS (2006). "Drug Insight: the role of leptin in human physiology and pathophysiology--emerging clinical applications". Nat Clin Pract Endocrinol Metab. 2 (6): 318–27. doi:10.1038/ncpendmet0196. PMID 16932309.

[pmid8717050-6] GreGreen ED, Maffei M, Braden VV, Proenca R, DeSilva U, Zhang Y, Chua SC Jr, Leibel RL, Weissenbach J, Friedman JM (1995). "The human obese (OB) gene: RNA expression pattern and mapping on the physical, cytogenetic, and genetic maps of chromosome 7". Genome Res. 5 (1): 5–12. doi:10.1101/gr.5.1.5. PMID 8717050.CS1 održavanje: više imena: authors list (link)

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