Role of the peroxisome proliferator-activated receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene expression.

The peroxisome proliferator activated receptors (PPARs) and their effects on lipid metabolism and adipocyte differentiation

The key roles of elongases and desaturases in mammalian fatty acid metabolism: Insights from transgenic mice.

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.

Regulation of gene expression by dietary fat

Polyunsaturated fatty acids (PUFA) of the n-6 and n-3 families inhibit transcription of a number of hepatic lipogenic and glycolytic genes, e.g. fatty acid synthase. In contrast, saturated and monounsaturated fatty acids exert no suppressive action on lipogenic gene expression. The unique PUFA regulation of gene expression extends beyond the liver to include genes such as adipocyte glucose transporter-4, lymphocyte stearoyl-CoA desaturase 2, and interleukins. Some of the transcriptional effects of PUFA appear to be mediated by eicosanoids, but PUFA suppression of lipogenic and glycolytic genes is independent of eicosanoid synthesis and appears to involve a nuclear mechanism directly modified by PUFA. With the recent cloning of a fatty acid-activated nuclear factor termed peroxisome-proliferator-activated receptor (PPAR) has come the suggestion that PPAR may be the PUFA response factor. This review, however, presents several lines of evidence that indicate that the PPAR and n-6 and n-3 PUFA regulation of lipogenic and glycolytic gene transcription involve separate and independent mechanisms. Thus PPAR appears not to be the PUFA response factor.

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N-3 polyunsaturated fatty acid regulation of hepatic gene transcription.

On the mechanism of induction of the enzyme systems for peroxisomal β-oxidation of fatty acids in rat liver by diets rich in partially hydrogenated fish oil

Jon Kvannes

Papers

On the mechanism of induction of the enzyme systems for peroxisomal β-oxidation of fatty acids in rat liver by diets rich in partially hydrogenated fish oil

The peroxisomal β-oxidation enzyme system of rat heart. Basal level and effect of the peroxisome proliferator clofibrate

A fluorometric assay of acyl-CoA oxidase activity by a coupled peroxidatic reaction: elimination of interfering side reactions.

On the mechanism of stimulation of peroxisomal beta-oxidation in rat heart by partially hydrogenated fish oil.

Rapid and sensitive assay of ornithine decarboxylase activity by high-performance liquid chromatography of the o-phthalaldehyde derivative putrescine