Author/Editor		Fon-Tacer, Klementina
Title		Citokromi P450, jedrni receptorji in fibroblastni rastni dejavniki - nove endokribne osi kot potencialna prijemališča za zdravljenje presnovnih bolezni
Translated title		Cytochromes P450, nuclear receptors, and fibroblast growth factors - new endocrine axes as potential drug targets to treat metabolic disorders
Type		članek
Source		Zdrav Vestn
Vol. and No.		Letnik 78, št. 6-7
Publication year		2009
Volume		str. 309-14
Language		slo
Abstract		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. 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.
Descriptors		METABOLIC DISEASES CYTOCHROME P-450 FIBROBLAST GROWTH FACTOR TRANSCRIPTION FACTORS VITAMIN D PHOSPHATES BILE ACIDS AND SALTS FATTY ACIDS AGING