TitleRegulation of gene expression by dietary fat.
Publication TypeJournal Article
Year of Publication1999
AuthorsJump, DB, Clarke, SD
JournalAnnu Rev Nutr
Volume19
Pagination63-90
Date Published1999
ISSN0199-9885
KeywordsAnimals, Arteriosclerosis, Bacteria, Dietary Fats, Fatty Acids, Gene Expression Regulation, Humans, Hyperlipidemias, Neoplasms, Yeasts
Abstract
 

Dietary fat is an important macronutrient for the growth and development of all organisms. In addition to its role as an energy source and its effects on membrane lipid composition, dietary fat has profound effects on gene expression, leading to changes in metabolism, growth, and cell differentiation. The effects of dietary fat on gene expression reflect an adaptive response to changes in the quantity and type of fat ingested. Specific fatty acid-regulated transcription factors have been identified in bacteria, amphibians, and mammals. In mammals, these factors include peroxisome proliferator-activated receptors (PPAR alpha, -beta, and -gamma), HNF4 alpha, NF kappa B, and SREBP1c. These factors are regulated by (a) direct binding of fatty acids, fatty acyl-coenzyme A, or oxidized fatty acids; (b) oxidized fatty acid (eicosanoid) regulation of G-protein-linked cell surface receptors and activation of signaling cascades targeting the nucleus; or (c) oxidized fatty acid regulation of intracellular calcium levels, which affect cell signaling cascades targeting the nucleus. At the cellular level, the physiological response to fatty acids will depend on (a) the quantity, chemistry, and duration of the fat ingested; (b) cell-specific fatty acid metabolism (oxidative pathways, kinetics, and competing reactions); (c) cellular abundance of specific nuclear and membrane receptors; and (d) involvement of specific transcription factors in gene expression. These mechanisms are involved in the control of carbohydrate and lipid metabolism, cell differentiation and growth, and cytokine, adhesion molecule, and eicosanoid production. The effects of fatty acids on the genome provide new insight into how dietary fat might play a role in health and disease.

DOI10.1146/annurev.nutr.19.1.63
Alternate JournalAnnu. Rev. Nutr.
PubMed ID10448517
Grant ListR01 DK043220 / DK / NIDDK NIH HHS / United States
DK43220 / DK / NIDDK NIH HHS / United States
DK46363 / DK / NIDDK NIH HHS / United States
DK53872 / DK / NIDDK NIH HHS / United States