Details

Autor(en) / Beteiligte

• JUMP, Donald B
• BOTOLIN, Daniela
• YUN WANG
• JINGHUA XU
• CHRISTIAN, Barbara
• DEMEURE, Olivier

Titel

Fatty acid regulation of hepatic gene transcription

Ist Teil von

• The Journal of nutrition, 2005-11, Vol.135 (11), p.2503-2506

Ort / Verlag

Bethesda, MD: American Society for Nutritional Sciences

Erscheinungsjahr

2005

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Dietary fat regulates gene expression by controlling the activity or abundance of key transcription factors. In vitro binding and cell culture studies have identified many transcription factors as prospective targets for fatty acid regulation, including peroxisome proliferator-activated receptors (PPARalpha, beta, gamma1, and gamma2), sterol regulatory element binding protein-1c (SREBP-1c), hepatic nuclear factors (HNF-4alpha and gamma), retinoid X receptor (RXRalpha), liver X receptor (LXRalpha), and others. In vivo studies established that PPARalpha- and SREBP-1c-regulated genes are key targets for PUFA control of hepatic gene expression. PUFA activate PPARalpha by direct binding, leading to the induction of hepatic fatty acid oxidation. PUFA inhibit hepatic fatty acid synthesis by suppressing SREBP-1c nuclear abundance through several mechanisms, including suppression of SREBP-1c gene transcription and enhancement of proteasomal degradation and mRNA(SREBP1c) decay. Changes in intracellular nonesterified fatty acids (NEFA) correlate well with changes in PPARalpha activity and mRNA(SREBP-1c) abundance. Several mechanisms regulate intracellular NEFA composition, including fatty acid transport, acyl CoA synthetases and thioesterases, fatty acid elongases and desaturases, neutral and polar lipid lipases, and fatty acid oxidation. Many of these mechanisms are regulated by PPARalpha or SREBP-1c. Together, these mechanisms control hepatic lipid composition and affect whole-body lipid composition.