Phytanic acid, a novel activator of uncoupling protein-1 gene transcription and brown adipocyte differentiation

Schlüter, Agatha; Barberà, Maria José; Iglesias, Roser; Giralt, Marta; Villarroya, Francesc

doi:10.1042/0264-6021:3620061

Cited by 28 publications

(35 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These results indicate that the effect on glucose uptake is not due to RXR activation, the common partner of these nuclear receptors. The differences between these nuclear receptors have been previously observed, for instance, adipogenesis was inhibited by an RAR-mediated event [29,30], whereas RXR-specific agonists promoted adipocyte differentiation [27].…”

Section: Discussionmentioning

confidence: 76%

“…We used the following dosages: rosiglitazone as PPARγ agonist, 10 μmol/l, a dose previously used in brown adipocytes [19]; TTNPB as RAR agonist, 10 μmol/l; and phytanic acid as RXR agonist, 20 μmol/l. The latter two doses are similar to those used in other studies in vitro [27]. To activate NR1HR we tested the synthetic compounds T0901317 and GW3965 at the optimal doses of 3 and 15 μmol/l, respectively, calculated from dose-response experiments (Fig.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Liver X receptor agonists ameliorate TNFα-induced insulin resistance in murine brown adipocytes by downregulating protein tyrosine phosphatase-1B gene expression

et al. 2006

View full text Add to dashboard Cite

Aims/hypothesis The nuclear receptors, including nuclear receptor subfamily 1, group H, member 3 (NR1HR, also known as liver X receptor [LXR]), are sensors of cholesterol metabolism and lipid biosynthesis that have recently been proposed as insulin sensitisers. TNFα has been described as a link between obesity and the development of insulin resistance, an important contributor to the pathogenesis of type 2 diabetes. Therefore, we decided to investigate the ability of NR1HR agonists to ameliorate TNFα-induced insulin resistance in brown adipocytes. Methods Primary brown adipocytes from rat fetuses, and from wild-type neonate mice and neonate mice deficient in the gene encoding protein tyrosine phosphatase-1B (Ptpn1, also known as Ptp1b) were cultured in the absence or presence of TNFα and different nuclear receptor agonists. Among them, the unrelated NR1HR ligands T0901317, GW3965 and (22R)-hydroxycholesterol were tested. After insulin stimulation, glucose uptake and solute carrier family 2 (facilitated glucose transporter), member 4 (SLC2A4, formerly known as GLUT4) translocation were measured. Next the insulin signalling cascade was determined by submitting cells to lysis, immunoprecipitation and immunoblotting. Results NR1HR agonists ameliorate TNFα-induced insulin resistance restoring completely insulin-stimulated glucose uptake and SLC2A4 translocation to plasma membrane. This effect is parallel to the recovery of the insulin cascade insulin receptor/IRS-2/phosphatidylinositol 3-kinase/protein kinase B, and could be due to the fact that T0901317 prevents the increase of PTPN1 production and phosphatase activity produced by TNFα. In this regard, Ptpn1-deficient brown adipocytes showed protection against insulin resistance by TNFα. Moreover, we observed that T0901317 produced in itself a significant increase over basal glucose uptake consistent with an increase of SLC2A4 protein content in plasma membrane, attributable to the activation of protein kinase ζ and/or the increase of Slc2a4 expression. Conclusions/interpretation Nuclear receptors NR1HR are interesting potential targets for drug treatment of insulin resistance. Keywords

show abstract

Section: Discussionmentioning

confidence: 76%

Section: Resultsmentioning

confidence: 99%

Liver X receptor agonists ameliorate TNFα-induced insulin resistance in murine brown adipocytes by downregulating protein tyrosine phosphatase-1B gene expression

et al. 2006

View full text Add to dashboard Cite

show abstract

“…Previous work has shown that the gene promoter of UCP1, the speci¢c molecular marker of di¡er-entiated brown adipocytes, was highly sensitive to phytanic acid [8]. To test the action of pristanic acid on the UCP1 gene promoter, the HIB-1B brown adipocyte-derived cell line was used.…”

Section: E¡ects Of Pristanic Acid and Phytanic Acid On Ucp1 Genementioning

confidence: 99%

Phytanic acid, but not pristanic acid, mediates the positive effects of phytol derivatives on brown adipocyte differentiation

et al. 2002

Self Cite

View full text Add to dashboard Cite

The phytol derivatives phytanic acid and pristanic acid may activate nuclear hormone receptors and influence gene expression and cell differentiation. Phytanic acid induces brown adipocyte differentiation. It was determined that brown fat and brown adipocytes are sites of high gene expression of phytanoylCoA hydroxylase, the enzyme required for initiation of peroxisomal K K-oxidation of phytanic acid. However, the effects of phytanic acid were not mediated by its K K-oxidation product pristanic acid, which did not promote brown adipocyte differentiation or stimulate transcription of the uncoupling protein-1 gene. Moreover, acute cold exposure of mice caused a dramatic mobilization of the phytanic acid stores in brown adipose tissue thus suggesting that a high local exposure to phytanic acid in brown fat may contribute to signalling adaptive changes in the tissue in response to thermogenic activation. ß

show abstract

“…PA has also been shown to induce adipocyte differentiation [129,130]. The origin of PA, which can also give rise to Refsum syndrome in which phytanoyl-CoA-hydroxylase is defective, is somewhat unclear [131].…”

mentioning

confidence: 99%

The Metabolic Plant Feedback Hypothesis: How Plant Secondary Metabolites Nonspecifically Impact Human Health

Gertsch

2016

Planta Med

View full text Add to dashboard Cite

Humans can ingest gram amounts of plant secondary metabolites daily through diet. Many of these phytochemicals are bioactive beyond our current understanding because they act through weak negative biological feedback mechanisms, undetectable in vitro. Homeostatic-type assessments shed light on the evolutionary implications of the human diet from plants, giving rise to the metabolic plant feedback hypothesis. The hypothesis states that ancient diets rich in carbohydrates coincide with bulk dietary phytochemicals that act as nonspecific inhibitors of metabolic and inflammatory processes. Consequently, food-derived phytochemicals are likely to be equally effective as herbal medicines for these indications. In addition to the ubiquitous flavonoids, terpenoids, and fatty acids in the diet, the likely impact of chronic chlorophyll ingestion on human health is discussed, and data on its modulation of blood glucose levels are presented. A major deduction of this hypothesis is that starchy diets lacking plant secondary metabolites are associated with multimorbidity (lifestyle diseases) including obesity, type 2 diabetes, and cardiovascular disease. It is proposed that the intake of leafy vegetables, spices, and herbal remedies rich in phytochemicals matches the transition and genetic adaptation to early agriculture, playing a compensatory role in the mismatch of old genes and new diets.

show abstract

Phytanic acid, a novel activator of uncoupling protein-1 gene transcription and brown adipocyte differentiation

Cited by 28 publications

References 39 publications

Liver X receptor agonists ameliorate TNFα-induced insulin resistance in murine brown adipocytes by downregulating protein tyrosine phosphatase-1B gene expression

Liver X receptor agonists ameliorate TNFα-induced insulin resistance in murine brown adipocytes by downregulating protein tyrosine phosphatase-1B gene expression

Phytanic acid, but not pristanic acid, mediates the positive effects of phytol derivatives on brown adipocyte differentiation

The Metabolic Plant Feedback Hypothesis: How Plant Secondary Metabolites Nonspecifically Impact Human Health

Contact Info

Product

Resources

About