The chlorophyll-derived metabolite phytanic acid induces white adipocyte differentiation

Abstract

Phytanic acid is a derivative of the phytol side-chain of chlorophyll. It appears in humans following the ingestion of fatcontaining foods and is present in human blood at a low micromolar concentration. It may activate retinoid X receptors (RXR) or peroxisome proliferator-activated receptor (PPAR) a in vitro. Phytanic acid induced the adipocyte differentiation of 3T3-L1 cells in culture as assessed by accumulation of lipid droplets and induction of the aP2 mRNA marker. This effect was mimicked by a synthetic activator of RXR but not by a PPARa agonist or by palmitic acid. In human pre-adipocytes in primary culture, phytanic acid also induced adipocyte differentiation. These findings indicate that phytanic acid may act as a natural rexinoid in adipose cells and suggest a potential use in the treatment of human type 2 diabetes and obesity.

Thiamine pyrophosphate: An essential cofactor for the α-oxidation in mammals – implications for thiamine deficiencies?

“…Another, and probably more important, mechanism to be considered is the modulation of transcription. Phytanic acid has been shown to bind and activate the nuclear receptors RXR [45][46][47] and PPAR-α [47], to enhance transcription of uncoupling protein-1 [48] and of fatty acid binding protein [49], and to induce adipocyte differentiation [48,50]. Other reported cellular effects of phytanic acid are nitric oxide-dependent apoptosis in vascular smooth muscle [51], morphological changes in retinal pigment epithelial cells, in particular generalized swelling, presence of lipid vacuoles and loss of apical microvilli, which are also seen in the retina of Refsum disease patients [52], and cytosolic calcium release, increase in reactive oxygen species and apoptosis due to mitochondrial impairment in rat hippocampal astrocytes [53,54].…”

Effects of Rilpivirine on Human Adipocyte Differentiation, Gene Expression, and Release of Adipokines and Cytokines

“…Human adipocyte precursor cells from healthy individuals, obtained from Advancell (Barcelona, Spain), were cultured as previously reported (20). After cells had reached 80% confluence, differentiation was induced by treating cells with Dulbecco's modified Eagle's medium (DMEM)-F12 medium containing 33 M biotin, 17 M sodium pantothenate, 200 nM insulin, 25 nM dexamethasone, 0.5 mM IBMX (3-isobutyl-1-methylxanthine), 2 M rosiglitazone, and 0.2 nM triiodothyronine.…”

IDH1 gene transcription is sterol regulated and activated by SREBP-1a and SREBP-2 in human hepatoma HepG2 cells

“…Several metabolic functions for phytanic acid have been reported: regulation of glucose metabolism in primary rat hepatocytes by acting as an agonist to peroxisome proliferator-activated receptors (PPARs) (21,22) and retinoid X receptor (RXR) (23); white adipocyte differentiation (24); and activation of uncoupling protein-1 gene transcription and brown adipocyte differentiation (25). In the autosomal disorder Refsum's disease, ␣ -oxidation of phytanic acid is affected in some, but not all, cases, and accumulation of this acid is observed in various tissues (26).…”