Citokromi P450, jedrni receptorji in fibroblastni rastni dejavniki - nove endokrine osi kot potencialna prijemališca za zdravljenje presnovnih bolezni

Translated title of the contribution: Cytochromes P450, nuclear receptors, and fibroblast growth factors - New en docr ine axes as potential dr ug targ ets to treat metabolic disorders

Klementina Fon Tacer

Research output: Contribution to journalArticle

Abstract

Background Coordinate action of endocrine and nervous system enables adaptation of higher organisms to constant changes in the environment. Fibroblast growth factors (FGFs) primarily regulate embryonic and organ development, however, FGF19 subfamily members despite the name act in an endocrine fashion. The studies of endocrine FGFs resulted in the discovery of new endocrine axes, composed of small lipophilic molecules and members of three protein families: cytochromes P450, nuclear receptors, and FGFs. Cytochromes P450 are enzymes responsible for metabolism of different lipid molecules. Nuclear receptors bind lipid metabolites and act as metabolic sensors. They become activated and as transcriptional factors turn on expression of endocrine FGFs. eFGFs regulate metabolic pathways in target organs that express specific FGF receptor/coreceptor pair. FGF15/19 is expressed in the small intestine and is involved in the postprandial bile acid negative feedback loop in the liver. FGF21 is liver-borne fasting hormone that induces fat utilization. FGF23 is expressed in bone and acts on kidney to regulate phosphate and vitamin D metabolism.Conclusions We describe herein three new endocrine axes that were probably developed for fine tuning metabolite concentration within narrow physiological limits and prevent their toxicity in excess. They play important role in the pathophysiology underlying diverse metabolic disorders and are expected to be potential targets for therapeutic interventions.

Original languageUndefined
Pages (from-to)309-314
Number of pages6
JournalZdravniski Vestnik
Volume78
Issue number6-7
StatePublished - Jun 2009

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Fibroblast Growth Factors
Cytoplasmic and Nuclear Receptors
Cytochrome P-450 Enzyme System
Fibroblast Growth Factor Receptors
Endocrine System
Liver
Metabolic Networks and Pathways
Bile Acids and Salts
Lipid Metabolism
Vitamin D
Nervous System
Small Intestine
Embryonic Development
Names
Fasting
Fats
Phosphates
Hormones
Kidney
Lipids

Keywords

  • Aging
  • Bile acid
  • Fatty acid
  • Metabolic syndrome
  • Metabolism
  • Phosphate
  • Vitamin D

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Citokromi P450, jedrni receptorji in fibroblastni rastni dejavniki - nove endokrine osi kot potencialna prijemališca za zdravljenje presnovnih bolezni. / Tacer, Klementina Fon.

In: Zdravniski Vestnik, Vol. 78, No. 6-7, 06.2009, p. 309-314.

Research output: Contribution to journalArticle

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abstract = "Background Coordinate action of endocrine and nervous system enables adaptation of higher organisms to constant changes in the environment. Fibroblast growth factors (FGFs) primarily regulate embryonic and organ development, however, FGF19 subfamily members despite the name act in an endocrine fashion. The studies of endocrine FGFs resulted in the discovery of new endocrine axes, composed of small lipophilic molecules and members of three protein families: cytochromes P450, nuclear receptors, and FGFs. Cytochromes P450 are enzymes responsible for metabolism of different lipid molecules. Nuclear receptors bind lipid metabolites and act as metabolic sensors. They become activated and as transcriptional factors turn on expression of endocrine FGFs. eFGFs regulate metabolic pathways in target organs that express specific FGF receptor/coreceptor pair. FGF15/19 is expressed in the small intestine and is involved in the postprandial bile acid negative feedback loop in the liver. FGF21 is liver-borne fasting hormone that induces fat utilization. FGF23 is expressed in bone and acts on kidney to regulate phosphate and vitamin D metabolism.Conclusions We describe herein three new endocrine axes that were probably developed for fine tuning metabolite concentration within narrow physiological limits and prevent their toxicity in excess. They play important role in the pathophysiology underlying diverse metabolic disorders and are expected to be potential targets for therapeutic interventions.",
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