PPARalpha is a key regulator of hepatic FGF21.
paper
Cited
Public
Unavailable
- Authors
- LundΓ₯sen, Thomas; Hunt, Mary C; Nilsson, Lisa-Mari; Sanyal, Sabyasachi; Angelin, Bo; Alexson, Stefan E H; Rudling, Mats
- Year
- 2007
- Journal
- Biochemical and biophysical research communications
- PMID
- 17601491
- DOI
- 10.1016/j.bbrc.2007.06.068
The metabolic regulator fibroblast growth factor 21 (FGF21) has antidiabetic properties in animal models of diabetes and obesity. Using quantitative RT-PCR, we here show that the hepatic gene expression of FGF21 is regulated by the peroxisome proliferator-activated receptor alpha (PPARalpha). Fasting or treatment of mice with the PPARalpha agonist Wy-14,643 induced FGF21 mRNA by 10-fold and 8-fold, respectively. In contrast, FGF21 mRNA was low in PPARalpha deficient mice, and fasting or treatment with Wy-14,643 did not induce FGF21. Obese ob/ob mice, known to have increased PPARalpha levels, displayed 12-fold increased hepatic FGF21 mRNA levels. The potential importance of PPARalpha for FGF21 expression also in human liver was shown by Wy-14,643 induction of FGF21 mRNA in human primary hepatocytes, and PPARalpha response elements were identified in both the human and mouse FGF21 promoters. Further studies on the mechanisms of regulation of FGF21 by PPARalpha in humans will be of great interest.
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| Possible role of fibroblast growth factor 21 on atherosclerosis via amelioration of endoplasmic reticulum stress-mediated apoptosis in apoE(-/-) mice. | Wu X et al. | β | 2015 | β |
| Practical prospects for boosting hepatic production of the "pro-longevity" hormone FGF21. | McCarty MF | β | 2015 | β |
| Rapid increase in fibroblast growth factor 21 in protein malnutrition and its impact on growth and lipid metabolism. | Ozaki Y et al. | β | 2015 | β |
| Recombinant murine fibroblast growth factor 21 ameliorates obesity-related inflammation in monosodium glutamate-induced obesity rats. | Wang WF et al. | β | 2015 | β |
| Research Perspectives on the Regulation and Physiological Functions of FGF21 and its Association with NAFLD. | Inagaki T | β | 2015 | β |
| The Fibroblast Growth Factor signaling pathway. | Ornitz DM et al. | β | 2015 | β |
| The role of fibroblast growth factor 21 in the pathogenesis of non-alcoholic fatty liver disease and implications for therapy. | Liu J et al. | β | 2015 | β |
| Tissue-specific actions of the metabolic hormones FGF15/19 and FGF21. | Owen BM et al. | β | 2015 | β |
| Transcriptome Analysis of K-877 (a Novel Selective PPARΞ± Modulator (SPPARMΞ±))-Regulated Genes in Primary Human Hepatocytes and the Mouse Liver. | Raza-Iqbal S et al. | β | 2015 | β |
| Ξ±-Lipoic acid as a triglyceride-lowering nutraceutical. | Pashaj A et al. | β | 2015 | β |
| Alpha lipoic acid induces hepatic fibroblast growth factor 21 expression via up-regulation of CREBH. | Bae KH et al. | β | 2014 | β |
| ATF4- and CHOP-dependent induction of FGF21 through endoplasmic reticulum stress. | Wan XS et al. | β | 2014 | β |
| Determinants of GH resistance in malnutrition. | Fazeli PK et al. | β | 2014 | β |
| Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on hormones of energy balance in a TCDD-sensitive and a TCDD-resistant rat strain. | LindΓ©n J et al. | β | 2014 | β |
| Exendin-4 regulates lipid metabolism and fibroblast growth factor 21 in hepatic steatosis. | Lee J et al. | β | 2014 | β |
| FGF-21 and skeletal remodeling during and after lactation in C57BL/6J mice. | Bornstein S et al. | β | 2014 | β |
| FGF21 expression and release in muscle cells: involvement of MyoD and regulation by mitochondria-driven signalling. | Ribas F et al. | β | 2014 | β |
| Fibroblast growth factor 21: a promising therapeutic target in obesity-related diseases. | Cheung BM et al. | β | 2014 | β |
| Fibroblast growth factor 21 is not required for the reductions in circulating insulin-like growth factor-1 or global cell proliferation rates in response to moderate calorie restriction in adult mice. | Thompson AC et al. | β | 2014 | β |
| Fibroblast growth factor 21, the endocrine FGF pathway and novel treatments for metabolic syndrome. | Zhang J et al. | β | 2014 | β |
| Fibroblast growth factor (Fgf) 21 is a novel target gene of the aryl hydrocarbon receptor (AhR). | Cheng X et al. | β | 2014 | β |
| Glucagon is essential for adaptive thermogenesis in brown adipose tissue. | Kinoshita K et al. | β | 2014 | β |
| Glucagon stimulates hepatic FGF21 secretion through a PKA- and EPAC-dependent posttranscriptional mechanism. | Cyphert HA et al. | β | 2014 | β |
| Hepatic FGF21 production is increased in late pregnancy in the mouse. | Cui Y et al. | β | 2014 | β |
| Hepatic mTORC1 controls locomotor activity, body temperature, and lipid metabolism through FGF21. | Cornu M et al. | β | 2014 | β |
| Improved glucose tolerance in insulin-resistant rats after pea hull feeding is associated with changes in lipid metabolism-targeted transcriptome. | Chan CB et al. | β | 2014 | β |
| Increased fibroblast growth factor 21 expression in high-fat diet-sensitive non-human primates (Macaca mulatta). | Nygaard EB et al. | β | 2014 | β |
| Integrated physiology and systems biology of PPARΞ±. | Kersten S | β | 2014 | β |
| Interplay between FGF21 and insulin action in the liver regulates metabolism. | Emanuelli B et al. | β | 2014 | β |
| Lifelong caloric restriction reprograms hepatic fat metabolism in mice. | Kuhla A et al. | β | 2014 | β |
| Liver-enriched transcription factor CREBH interacts with peroxisome proliferator-activated receptor Ξ± to regulate metabolic hormone FGF21. | Kim H et al. | β | 2014 | β |
| Novel sandwich immunoassays for the measurement of total and active FGF21. | Umberger TS et al. | β | 2014 | β |
| Nrf2 induces fibroblast growth factor 21 in diabetic mice. | Furusawa Y et al. | β | 2014 | β |
| Regulators of human white adipose browning: evidence for sympathetic control and sexual dimorphic responses to sprint interval training. | Scalzo RL et al. | β | 2014 | β |
| Skeletal muscle mitochondrial uncoupling drives endocrine cross-talk through the induction of FGF21 as a myokine. | Keipert S et al. | β | 2014 | β |
| The role of fibroblast growth factor 21 in the pathogenesis of liver disease: a novel predictor and therapeutic target. | Liu WY et al. | β | 2014 | β |
| Transcriptional regulation of fibroblast growth factor 21 expression. | Bae KH et al. | β | 2014 | β |
| Up-regulation of endoplasmic reticulum stress induced genes of the unfolded protein response in the liver of periparturient dairy cows. | Gessner DK et al. | β | 2014 | β |
| Activation of Liver FGF21 in hepatocarcinogenesis and during hepatic stress. | Yang C et al. | β | 2013 | β |
| Adverse effects of excessive leucine intake depend on dietary protein intake: a transcriptomic analysis to identify useful biomarkers. | Imamura W et al. | β | 2013 | β |
| Bitter melon extract attenuating hepatic steatosis may be mediated by FGF21 and AMPK/Sirt1 signaling in mice. | Yu Y et al. | β | 2013 | β |
| Concurrent activation of liver X receptor and peroxisome proliferator-activated receptor alpha exacerbates hepatic steatosis in high fat diet-induced obese mice. | Gao M et al. | β | 2013 | β |
| Expression of fibroblast growth factor 21 in the liver of dairy cows in the transition period and during lactation. | Schlegel G et al. | β | 2013 | β |
| FGF21 mediates the lipid metabolism response to amino acid starvation. | De Sousa-Coelho AL et al. | β | 2013 | β |
| Fibroblast growth factor 21: a novel metabolic regulator from pharmacology to physiology. | Li H et al. | β | 2013 | β |
| Fibroblast growth factor 21 as an emerging metabolic regulator: clinical perspectives. | Woo YC et al. | β | 2013 | β |
| Fibroblast growth factor 21 is not required for the antidiabetic actions of the thiazoladinediones. | Adams AC et al. | β | 2013 | β |
| Fibroblast growth factor 21 mediates specific glucagon actions. | Habegger KM et al. | β | 2013 | β |
| Fibroblast growth factor 21 predicts the metabolic syndrome and type 2 diabetes in Caucasians. | Bobbert T et al. | β | 2013 | β |
| Influence of growth hormone on circulating fibroblast growth factor 21 levels in humans. | Lundberg J et al. | β | 2013 | β |
| Protective effect of FGF21 on type 1 diabetes-induced testicular apoptotic cell death probably via both mitochondrial- and endoplasmic reticulum stress-dependent pathways in the mouse model. | Jiang X et al. | β | 2013 | β |
| Recruitment of histone methyltransferase G9a mediates transcriptional repression of Fgf21 gene by E4BP4 protein. | Tong X et al. | β | 2013 | β |
| Serum levels of the adipokine fibroblast growth factor-21 are increased in preeclampsia. | Stepan H et al. | β | 2013 | β |
| Stress heats up the adipocyte. | Fisher FM et al. | β | 2013 | β |
| Activating transcription factor 4-dependent induction of FGF21 during amino acid deprivation. | De Sousa-Coelho AL et al. | β | 2012 | β |
| Activation of the farnesoid X receptor induces hepatic expression and secretion of fibroblast growth factor 21. | Cyphert HA et al. | β | 2012 | β |
| Circulating fibroblast growth factors as metabolic regulators--a critical appraisal. | Angelin B et al. | β | 2012 | β |
| Cobalt chloride decreases fibroblast growth factor-21 expression dependent on oxidative stress but not hypoxia-inducible factor in Caco-2 cells. | Liu Y et al. | β | 2012 | β |
| Conjugated linoleic acid induces hepatic expression of fibroblast growth factor 21 through PPAR-Ξ±. | Yu J et al. | β | 2012 | β |
| Dietary moderately oxidized oil induces expression of fibroblast growth factor 21 in the liver of pigs. | Varady J et al. | β | 2012 | β |
| Differential specificity of endocrine FGF19 and FGF21 to FGFR1 and FGFR4 in complex with KLB. | Yang C et al. | β | 2012 | β |
| Endocrine fibroblast growth factors 15/19 and 21: from feast to famine. | Potthoff MJ et al. | β | 2012 | β |
| Exercise increases serum fibroblast growth factor 21 (FGF21) levels. | Cuevas-Ramos D et al. | β | 2012 | β |
| FGF21 as a therapeutic reagent. | Zhao Y et al. | β | 2012 | β |
| FGF21 is increased by inflammatory stimuli and protects leptin-deficient ob/ob mice from the toxicity of sepsis. | Feingold KR et al. | β | 2012 | β |
| Fibroblast growth factor 21 promotes bone loss by potentiating the effects of peroxisome proliferator-activated receptor Ξ³. | Wei W et al. | β | 2012 | β |
| Fibroblast growth factor-21 regulates PPARΞ³ activity and the antidiabetic actions of thiazolidinediones. | Dutchak PA et al. | β | 2012 | β |
| Inhibition of intestinal bile acid transporter Slc10a2 improves triglyceride metabolism and normalizes elevated plasma glucose levels in mice. | LundΓ₯sen T et al. | β | 2012 | β |
| Lack of overt FGF21 resistance in two mouse models of obesity and insulin resistance. | Hale C et al. | β | 2012 | β |
| Liver X receptor negatively regulates fibroblast growth factor 21 in the fatty liver induced by cholesterol-enriched diet. | Uebanso T et al. | β | 2012 | β |
| Long-term fenofibrate therapy increases fibroblast growth factor 21 and retinol-binding protein 4 in subjects with type 2 diabetes. | Ong KL et al. | β | 2012 | β |
| Metabolic actions of fibroblast growth factor 21. | Cuevas-Ramos D et al. | β | 2012 | β |
| Metformin stimulates FGF21 expression in primary hepatocytes. | Nygaard EB et al. | β | 2012 | β |
| Modulating fibroblast growth factor 21 in hyperphagic OLETF rats with daily exercise and caloric restriction. | Fletcher JA et al. | β | 2012 | β |
| Peroxisome deficiency-induced ER stress and SREBP-2 pathway activation in the liver of newborn PEX2 knock-out mice. | Kovacs WJ et al. | β | 2012 | β |
| Plasma mannose-binding lectin is stimulated by PPARΞ± in humans. | Rakhshandehroo M et al. | β | 2012 | β |
| Ξ²Klotho is required for fibroblast growth factor 21 effects on growth and metabolism. | Ding X et al. | β | 2012 | β |
| Effects of short-term continuous subcutaneous insulin infusion on fasting plasma fibroblast growth factor-21 levels in patients with newly diagnosed type 2 diabetes mellitus. | Yang M et al. | β | 2011 | β |
| FGF21 reloaded: challenges of a rapidly growing field. | Kharitonenkov A et al. | β | 2011 | β |
| Fibroblast growth factor 21 is a metabolic regulator that plays a role in the adaptation to ketosis. | Domouzoglou EM et al. | β | 2011 | β |
| Hepatosteatosis in peroxisome deficient liver despite increased Ξ²-oxidation capacity and impaired lipogenesis. | Peeters A et al. | β | 2011 | β |
| Liver fat but not other adiposity measures influence circulating FGF21 levels in healthy young adult twins. | Tyynismaa H et al. | β | 2011 | β |
| Paradoxical regulation of human FGF21 by both fasting and feeding signals: is FGF21 a nutritional adaptation factor? | Uebanso T et al. | β | 2011 | β |
| Plasma FGF21 displays a circadian rhythm during a 72-h fast in healthy female volunteers. | Andersen B et al. | β | 2011 | β |
| Plasma FGF21 is elevated by the intense lipid mobilization of lactation. | Schoenberg KM et al. | β | 2011 | β |
| Serum FGF-21 levels in type 2 diabetic patients. | Cheng X et al. | β | 2011 | β |
| The link between fibroblast growth factor 21 and sterol regulatory element binding protein 1c during lipogenesis in hepatocytes. | Zhang Y et al. | β | 2011 | β |
| Thiazolidinediones are potent inducers of fibroblast growth factor 21 expression in the liver. | Oishi K et al. | β | 2011 | β |
| Bezafibrate induces plasminogen activator inhibitor-1 gene expression in a CLOCK-dependent circadian manner. | Oishi K et al. | β | 2010 | β |
| Control of steroid 21-oic acid synthesis by peroxisome proliferator-activated receptor alpha and role of the hypothalamic-pituitary-adrenal axis. | Wang T et al. | β | 2010 | β |
| Daily physical activity, fasting glucose, uric acid, and body mass index are independent factors associated with serum fibroblast growth factor 21 levels. | Cuevas-Ramos D et al. | β | 2010 | β |
| Fibroblast growth factor 21: from pharmacology to physiology. | Kliewer SA et al. | β | 2010 | β |
| Glucagon and lipid interactions in the regulation of hepatic AMPK signaling and expression of PPARalpha and FGF21 transcripts in vivo. | Berglund ED et al. | β | 2010 | β |
| Increased fibroblast growth factor 21 in obesity and nonalcoholic fatty liver disease. | Dushay J et al. | β | 2010 | β |
| Peroxisome proliferator-activated receptor alpha target genes. | Rakhshandehroo M et al. | β | 2010 | β |
| PPARs: diverse regulators in energy metabolism and metabolic diseases. | Wang YX | β | 2010 | β |
| Proxisome proliferator-activated receptor-Ξ± mediates high-fat, diet-enhanced daily oscillation of plasminogen activator inhibitor-1 activity in mice. | Hayashida S et al. | β | 2010 | β |
| Regulation of FGF21 expression and secretion by retinoic acid receptor-related orphan receptor alpha. | Wang Y et al. | β | 2010 | β |
| Serum fibroblast growth factor 21 levels in gestational diabetes mellitus in relation to insulin resistance and dyslipidemia. | Stein S et al. | β | 2010 | β |
| The Role of PPARΞ± Activation in Liver and Muscle. | Burri L et al. | β | 2010 | β |
| Transcriptional repressor E4-binding protein 4 (E4BP4) regulates metabolic hormone fibroblast growth factor 21 (FGF21) during circadian cycles and feeding. | Tong X et al. | β | 2010 | β |
| A very low carbohydrate ketogenic diet improves glucose tolerance in ob/ob mice independently of weight loss. | Badman MK et al. | β | 2009 | β |
| Circulating fibroblast growth factor 21 is induced by peroxisome proliferator-activated receptor agonists but not ketosis in man. | Christodoulides C et al. | β | 2009 | β |
| Endocrine fibroblast growth factors as regulators of metabolic homeostasis. | Kurosu H et al. | β | 2009 | β |
| Fenofibrate simultaneously induces hepatic fatty acid oxidation, synthesis, and elongation in mice. | Oosterveer MH et al. | β | 2009 | β |
| FGF21 induces PGC-1alpha and regulates carbohydrate and fatty acid metabolism during the adaptive starvation response. | Potthoff MJ et al. | β | 2009 | β |
| Fibroblast growth factor 21: an overview from a clinical perspective. | RydΓ©n M | β | 2009 | β |
| Fibroblast growth factor 21 controls glycemia via regulation of hepatic glucose flux and insulin sensitivity. | Berglund ED et al. | β | 2009 | β |
| Fibroblast growth factor 21-deficient mice demonstrate impaired adaptation to ketosis. | Badman MK et al. | β | 2009 | β |
| Fibroblast growth factor-21 is induced in human skeletal muscles by hyperinsulinemia. | Hojman P et al. | β | 2009 | β |
| Role of PPARΞ± in the control of torpor through FGF21-NPY pathway: From circadian clock to seasonal change in mammals. | Ishida N | β | 2009 | β |
| Serum concentrations and tissue expression of a novel endocrine regulator fibroblast growth factor-21 in patients with type 2 diabetes and obesity. | Mraz M et al. | β | 2009 | β |
| The Klotho gene family as a regulator of endocrine fibroblast growth factors. | Kurosu H et al. | β | 2009 | β |
| Torpor induction in mammals: recent discoveries fueling new ideas. | Melvin RG et al. | β | 2009 | β |
| Bezafibrate, a peroxisome proliferator-activated receptors agonist, decreases body temperature and enhances electroencephalogram delta-oscillation during sleep in mice. | Chikahisa S et al. | β | 2008 | β |
| Circadian expression of FGF21 is induced by PPARalpha activation in the mouse liver. | Oishi K et al. | β | 2008 | β |
| Effects of Momordica charantia on insulin resistance and visceral obesity in mice on high-fat diet. | Shih CC et al. | β | 2008 | β |
| FGF21 is an Akt-regulated myokine. | Izumiya Y et al. | β | 2008 | β |
| Fibroblast growth factor 21 corrects obesity in mice. | Coskun T et al. | β | 2008 | β |
| Inhibition of growth hormone signaling by the fasting-induced hormone FGF21. | Inagaki T et al. | β | 2008 | β |
| Partial resistance to peroxisome proliferator-activated receptor-alpha agonists in ZDF rats is associated with defective hepatic mitochondrial metabolism. | Satapati S et al. | β | 2008 | β |
| Plasma concentrations of fibroblast growth factors 19 and 21 in patients with anorexia nervosa. | DostΓ‘lovΓ‘ I et al. | β | 2008 | β |
| Sequential changes in the expression of genes involved in lipid metabolism in adipose tissue and liver in response to fasting. | Palou M et al. | β | 2008 | β |
| Serum FGF21 levels are increased in obesity and are independently associated with the metabolic syndrome in humans. | Zhang X et al. | β | 2008 | β |
| The circulating metabolic regulator FGF21 is induced by prolonged fasting and PPARalpha activation in man. | GΓ€lman C et al. | β | 2008 | β |
| Regulation of circadian gene expression in liver by systemic signals and hepatocyte oscillators. | Kornmann B et al. | β | 2007 | β |