The natural carotenoid astaxanthin, a <scp>PPAR</scp>‐α agonist and <scp>PPAR</scp>‐γ antagonist, reduces hepatic lipid accumulation by rewiring the transcriptome in lipid‐loaded hepatocytes

Jia, Yaoyao; Kim, Jin Young; Jun, Hee-Jin; Kim, Sun Joong; Lee, Ji Hae; Hoang, Minh Hien; Hwang, Kwang Yeon; Um, Soo‐Jong; Chang, Hyo Ihl; Lee, Sung Joon

doi:10.1002/mnfr.201100798

Cited by 109 publications

(81 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studies in HepG2 cells treated with genistein, another polyphenol that is the main soy isoflavone, induced the expression of PPARa at both messenger RNA (mRNA) and protein levels and enhanced expression of genes involved in fatty acid catabolism through activation of PPAR-a (34). Additional PPAR-a ligands from diet with hypolipidemic activity have been reported, such as the natural carotenoid abundant in seafood, astaxanthin, and the active compound extracted from the tomato, 9-oxo-10(E),12(E)-octadecadienoic acid (35,36).…”

Section: Natural and Synthetic Ppar-a Ligandsmentioning

confidence: 98%

PPAR-α as a Key Nutritional and Environmental Sensor for Metabolic Adaptation

Contreras¹,

Torres²,

Tovar³

2013

Advances in Nutrition

194

148

View full text Add to dashboard Cite

Peroxisome proliferator-activated receptors (PPARs) are transcription factors that belong to the superfamily of nuclear hormone receptors and regulate the expression of several genes involved in metabolic processes that are potentially linked to the development of some diseases such as hyperlipidemia, diabetes, and obesity. One type of PPAR, PPAR-α, is a transcription factor that regulates the metabolism of lipids, carbohydrates, and amino acids and is activated by ligands such as polyunsaturated fatty acids and drugs used to treat dyslipidemias. There is evidence that genetic variants within the PPARα gene have been associated with a risk of the development of dyslipidemia and cardiovascular disease by influencing fasting and postprandial lipid concentrations; the gene variants have also been associated with an acceleration of the progression of type 2 diabetes. The interactions between genetic PPARα variants and the response to dietary factors will help to identify individuals or populations who can benefit from specific dietary recommendations. Interestingly, certain nutritional conditions, such as the prolonged consumption of a protein-restricted diet, can produce long-lasting effects on PPARα gene expression through modifications in the methylation of a specific locus surrounding the PPARα gene. Thus, this review underlines our current knowledge about the important role of PPAR-α as a mediator of the metabolic response to nutritional and environmental factors.

show abstract

Section: Natural and Synthetic Ppar-a Ligandsmentioning

confidence: 98%

PPAR-α as a Key Nutritional and Environmental Sensor for Metabolic Adaptation

Contreras¹,

Torres²,

Tovar³

2013

Advances in Nutrition

194

148

View full text Add to dashboard Cite

show abstract

“…Indeed, apart from fatty acids, numerous other dietary components have been proposed to serve as PPARα agonists, including but not limited to the flavanoid cyanidin [152], the carotenoid astaxanthin [153], the plant triterpenoid ursolic acid [154], the plant stilbenoid pterostilbene [155], isohumulones in hops [156], soy isoflavones [157], and conjugated linoleic acid [158]. However, it is highly questionable whether intake of any of these compounds is high enough to lead to PPARα activation in vivo, especially taking into account the abundance of fatty acids in our diet and in the cell.…”

Section: Regulation Of Intermediary Metabolism By Pparα Upon Physiolomentioning

confidence: 99%

Integrated physiology and systems biology of PPARα

Kersten

2014

Molecular Metabolism

516

415

View full text Add to dashboard Cite

The Peroxisome Proliferator Activated Receptor alpha (PPARα) is a transcription factor that plays a major role in metabolic regulation. This review addresses the functional role of PPARα in intermediary metabolism and provides a detailed overview of metabolic genes targeted by PPARα, with a focus on liver. A distinction is made between the impact of PPARα on metabolism upon physiological, pharmacological, and nutritional activation. Low and high throughput gene expression analyses have allowed the creation of a comprehensive map illustrating the role of PPARα as master regulator of lipid metabolism via regulation of numerous genes. The map puts PPARα at the center of a regulatory hub impacting fatty acid uptake, fatty acid activation, intracellular fatty acid binding, mitochondrial and peroxisomal fatty acid oxidation, ketogenesis, triglyceride turnover, lipid droplet biology, gluconeogenesis, and bile synthesis/secretion. In addition, PPARα governs the expression of several secreted proteins that exert local and endocrine functions.

show abstract

“…128 In addition, astaxanthin was reported to reduce total cholesterol in mice and the cellular cholesterol in HepG2 hepatocytes and increase HDL-cholesterol concentrations in rats. 90,91,93 As mentioned earlier, lycopene increased the expression of PPARγ, LXRα, and ABCA1 and decreased cellular total cholesterol levels in human prostate LNCaP and DU145 cancer cells. 15,16 Lycopene or APO10LA reduced hepatic total cholesterol and elevated cholesterol-efflux genes in BCO2-knockout male mice.…”

Section: Pparγ In Anti-inflammatory Actions and Modification Of Cholementioning

confidence: 60%

“…It reduced lipid accumulation and cellular cholesterol and triglyceride concentrations by rewiring the transcriptome in lipid-loaded HepG2 hepatocytes. 93 However, astaxanthin improved the adipogenic differentiation potential of mouse neural progenitor cells. Astaxanthin-treated neural progenitor cells showed prominent fat formation and induced significant overexpression of adipogenesis-related AP and PPARγ mRNA.…”

Section: Other Carotenoidsmentioning

confidence: 99%

Role of PPARγ in the nutritional and pharmacological actions of carotenoids

Wang¹,

Shi²,

Gu³

et al. 2016

RRBC

View full text Add to dashboard Cite

Peroxisome proliferator-activated receptor gamma (PPARγ) has been shown to play an important role in the biological effects of carotenoids. The PPARγ-signaling pathway is involved in the anticancer effects of carotenoids. Activation of PPARγ partly contributes to the growth-inhibitory effects of carotenoids (β-carotene, astaxanthin, bixin, capsanthin, lutein, and lycopene) on breast cancer MCF7 cells, leukemia K562 cells, prostate cancer (LNCaP, DU145, and PC3 cells), and esophageal squamous cancer EC109 cells. PPARγ is the master regulator of adipocyte differentiation and adipogenesis. Downregulated PPARγ and PPARγ-target genes have been associated with the suppressive effects of β-carotene and lycopene on 3T3L1 and C3H10T1/2 adipocyte differentiation and adipogenesis. β-Carotene is cleaved centrally into retinaldehyde by BCO1, the encoding gene being a PPARγ-target gene. Retinaldehyde can be oxidized to retinoic acid and also be reduced to retinol. β-Carotene can also be cleaved asymmetrically into β-apocarotenals and β-apocarotenones by BCO2. The inhibitory effects of β-carotene on the development of adiposity and lipid storage are dependent substantially on BCO1-mediated production of retinoids. The effects of β-carotene on body adiposity were absent in BCO1-knockout mice. Retinoid metabolism is connected with the activity of PPARγ in the control of body-fat reserves. Retinoic acid, retinaldehyde, retinol, and β-apocarotenals exert suppressive effects on preadipocyte differentiation and adipogenesis via downregulation of PPARγ expression in cell culture. The molecular mechanisms underlying retinoic acid effects on adipose-tissue biology and the development of adiposity remain poorly understood. Adiposity can be affected by retinoids through long-lasting effects at critical developmental stages. Retinol saturase increases PPARγ-transcriptional activity and adipocyte differentiation. Other carotenoids that have been reported to suppress adipocyte differentiation and lipid accumulation in the main via modulation of PPARγ and PPARγ-target genes include astaxanthin, bixin, norbixin, β-cryptoxanthin, fucoxanthin and its metabolites, lycopene, apo-10'-lycopenoic acid, siphonaxanthin, and neoxanthin, except paprika pigments. Lutein, lycopene, and paprika carotenoids reduce proinflammatory cytokine levels by an induction of PPARγ in immune tissues and cells. Lycopene, apo-10'-lycopenoic acid, and astaxanthin might prevent atherosclerosis through modifying cholesterol metabolism via increasing PPARγ expression in macrophages.

show abstract

The natural carotenoid astaxanthin, a PPAR‐α agonist and PPAR‐γ antagonist, reduces hepatic lipid accumulation by rewiring the transcriptome in lipid‐loaded hepatocytes

Abstract: AX is a PPAR-α agonist and PPAR-γ antagonist, reduces hepatic lipid accumulation by rewiring the transcriptome in lipid-loaded hepatocytes.

Cited by 109 publications

References 43 publications

PPAR-α as a Key Nutritional and Environmental Sensor for Metabolic Adaptation

PPAR-α as a Key Nutritional and Environmental Sensor for Metabolic Adaptation

Integrated physiology and systems biology of PPARα

Role of PPARγ in the nutritional and pharmacological actions of carotenoids

Contact Info

Product

Resources

About

The natural carotenoid astaxanthin, a PPAR‐α agonist and PPAR‐γ antagonist, reduces hepatic lipid accumulation by rewiring the transcriptome in lipid‐loaded hepatocytes

Abstract: AX is a PPAR-α agonist and PPAR-γ antagonist, reduces hepatic lipid accumulation by rewiring the transcriptome in lipid-loaded hepatocytes.

Cited by 109 publications

References 43 publications

PPAR-α as a Key Nutritional and Environmental Sensor for Metabolic Adaptation

PPAR-α as a Key Nutritional and Environmental Sensor for Metabolic Adaptation

Integrated physiology and systems biology of PPARα

Role of PPAR&gamma; in the nutritional and pharmacological actions of carotenoids

Contact Info

Product

Resources

About

Role of PPARγ in the nutritional and pharmacological actions of carotenoids