Dataset Information

Phytanic acid activates PPAR? to promote beige adipogenic differentiation of preadipocytes.

ABSTRACT: A better understanding of the mechanisms of beige and brown adipogenesis is needed for developing strategies to prevent and treat obesity and associated metabolic disorders. Phytanic acid (PA) exists in a wide range of foods, especially in milk fat and marine foods, but its effects on obesity and beige adipogenesis remain poorly defined. The objective is to investigate the effects and regulatory mechanisms of PA in the beige adipogenesis. In 3T3-L1 preadipocytes, PA elevated the expression of brown adipogenic markers, suggesting that PA promotes beige adipogenic differentiation in committed adipogenic cells. In uncommitted C3H10T1/2 cells, while PA increased PGC1? expression, it did not increase brown adipogenic regulators PRDM16 or UCP1 expression, suggesting that PA had no significant effects on brown adipocyte commitment. PA also enhanced mitochondrial biogenesis and oxygen consumption. Promotion of both mitochondriogenesis and beige adipogenic differentiation were blocked by using PPAR? antagonist or with Ppar? knockdown, showing that PA-mediated beige/brown adipogenic differentiation is dependent on PPAR?. Additionally, the PA-regulated effect is independent on ?3-adrenergic receptor. Taken together, PA promotes beige adipogenic differentiation, but not the commitment of progenitor cells to the brown adipocyte lineage. PPAR? is a key mediator during PA-induced beige/brown adipogenic differentiation.

SUBMITTER: Wang H

PROVIDER: S-EPMC6537602 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Phytanic acid activates PPARα to promote beige adipogenic differentiation of preadipocytes.

Wang Hanning H Mao Xueying X Du Min M

The Journal of nutritional biochemistry 20190311

A better understanding of the mechanisms of beige and brown adipogenesis is needed for developing strategies to prevent and treat obesity and associated metabolic disorders. Phytanic acid (PA) exists in a wide range of foods, especially in milk fat and marine foods, but its effects on obesity and beige adipogenesis remain poorly defined. The objective is to investigate the effects and regulatory mechanisms of PA in the beige adipogenesis. In 3T3-L1 preadipocytes, PA elevated the expression of br ...[more]

PMID: 30951974

Similar Datasets

Project description:Obesity is a major global health issue that contributes to the occurrence of metabolic disorders. Based on this fact, understanding the underlying mechanisms and to uncover promising therapeutic approaches for obesity have attracted intense investigation. Brown adipose tissue (BAT) can help burns excess calories. Therefore, promoting White adipose tissue (WAT) browning and BAT activation is an attractive strategy for obesity treatment. MicroRNAs (miRNAs) are small, non-coding RNAs, which are involved in regulation of adipogenic processes and metabolic functions. Evidence is accumulating that miRNAs are important regulators for both brown adipocyte differentiation and white adipocyte browning. Here we report that the expression of miR-669a-5p increases during the adipogenic differentiation of 3T3-L1 and C3H10T1/2 adipocytes. miR-669a-5p supplementation promotes adipogenic differentiation and causes browning of 3T3-L1 and C3H10T1/2 cells. Moreover, the expression of miR-669a-5p is upregulated in iWAT of mice exposed to cold. These data demonstrate that miR-669a-5p plays a role in regulating adipocyte differentiation and fat browning.Abbreviations: Acadl: long-chain acyl-Coenzyme A dehydrogenase; Acadm: medium-chain acyl-Coenzyme A dehydrogenase; Acadvl: very long-chain acyl-Coenzyme A dehydrogenase, very long chain; Aco2: mitochondrial aconitase 2; BAT: brown adipose tissue; Bmper: BMP-binding endothelial regulator; Cpt1-b:carnitine palmitoyltransferase 1b; Cpt2: carnitine palmitoyltransferase 2; Crat: carnitine acetyltransferase; Cs: citrate synthase; C2MC: Chromosome 2 miRNA cluster; DMEM: Dulbecco's modified Eagle medium; eWAT: epididymal white adipose tissue; ETC: electron transport chain; FAO: fatty acid oxidation; Fabp4:fatty acid binding protein 4; FBS: fetal bovine serum; Hadha: hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha; Hadhb: hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta; HFD: high fat diet; Idh3a: isocitrate dehydrogenase 3 alpha; iWAT: inguinal subcutaneous white adipose tissue; Lpl: lipoprotein lipase; Mdh2: malate dehydrogenase 2; NBCS: NewBorn Calf Serum; mt-Nd1: mitochondrial NADH dehydrogenase 1; Ndufb8:ubiquinone oxidoreductase subunit B8; Nrf1: nuclear respiratory factor 1; Pgc1α: peroxisome proliferative activated receptor gamma coactivator 1 alpha; Pgc1b: peroxisome proliferative activated receptor, gamma, coactivator 1 beta; Pparγ: peroxisome proliferator activated receptor gamma; Prdm16: PR domain containing 16; Rgs4: regulator of G-protein signaling 4; Sdhb: succinate dehydrogenase complex, subunit B; Sdhc: succinate dehydrogenase complex, subunit C; Sdhd: succinate dehydrogenase complex, subunit D; Sh3d21: SH3 domain containing 21; Sfmbt2: Scm-like with four mbt domains 2; TG: triglyceride; TCA: tricarboxylic acid cycle; Tfam: transcription factor A, mitochondrial; TMRE: tetramethylrhodamine, methyl ester; Ucp1: uncoupling protein 1; Uqcrc2: ubiquinol cytochrome c reductase core protein 2; WAT: White adipose tissue.

Project description:BACKGROUND:Although the 3T3-L1 preadipocyte cell line represents an informative model for in vitro adipogenesis research, primary cultured cells are often needed to understand particular human or animal metabolic phenotypes. As demonstrated by in vitro cultured preadipocytes from large mammalian species, primary cultured cells require specific adipogenic differentiation conditions different to that of the 3T3-L1 cell line. These conditions are also species-specific and require optimization steps. However, efficient protocols to differentiate primary preadipocytes using alternative species to rodents are scarce. Sheep represent an amenable animal model for fetal biology and developmental origins of health and disease studies. In this work, we present with the first detailed procedure to efficiently differentiate primary fetal and adult ovine preadipocytes. METHODS:Fetal and adult ovine adipose and skin tissue harvest, preadipocyte and fibroblast isolation, proliferation, and standardization and optimization of a new adipogenic differentiation protocol. Use of commercial cell lines (3T3-L1 and NIH-3T3) for validation purposes. Oil red O stain and gene expression were used to validate adipogenic differentiation. ANOVA and Fisher's exact test were used to determine statistical significance. RESULTS:Our optimized adipogenic differentiation method included a prolonged adipogenic cocktail exposure time from 2 to 8 days, higher insulin concentration, and supplementation with the peroxisome proliferator-activated receptor gamma (PPARγ) agonist, rosiglitazone. This protocol was optimized for both, fetal and adult preadipocytes. CONCLUSIONS:Our protocol enables successful adipogenic differentiation of fetal and adult ovine preadipocytes. This work demonstrates that compared to the 3T3-L1 cell line, fetal ovine preadipocytes require a longer exposure to the differentiation cocktail, and the need for IMBX, dexamethasone, and/or the PPARγ agonist rosiglitazone through the terminal differentiation phase. They also require higher insulin concentration during differentiation to enhance lipid accumulation and similar to human primary preadipocytes, PPARγ agonist supplementation is also required for ovine adipogenic differentiation. This work highlights species-specific differences requirements for adipogenic differentiation and the need to develop standardized methods to investigate comparative adipocyte biology.

Dataset Information

Phytanic acid activates PPAR? to promote beige adipogenic differentiation of preadipocytes.

Publications

Phytanic acid activates PPARα to promote beige adipogenic differentiation of preadipocytes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets