FGF21 lowers plasma triglycerides by accelerating lipoprotein catabolism in white and brown adipose tissues

Schlein, Christian; Talukdar, Saswata; Heine, Markus; Fischer, Alexander W.; Krott, Lucia M.; Nilsson, Stefan K.; Brenner, Martin; Heeren, Joerg; Scheja, Ludger

doi:10.1016/j.atherosclerosis.2016.07.024

Cited by 9 publications

(10 citation statements)

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“…Paradoxically, amelioration of obesity via reduced adiposity is one of the key hallmarks of the in vivo action of FGF21. As recently noted, FGF21 is able to promote adipose tissue lipolysis in mice by indirect mechanisms .…”

Section: Fgf21 and Lipolysismentioning

confidence: 57%

Fibroblast growth factor 21 night watch: advances and uncertainties in the field

Kharitonenkov

DiMarchi

2016

J Intern Med

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Abstract. Kharitonenkov A, DiMarchi R (Indiana University Bloomington, Bloomington, IN, USA). Fibroblast growth factor 21 night watch: advances and uncertainties in the field (Review). J Intern Med 2017; 281: 233-246.Fibroblast growth factor (FGF) 21 belongs to a hormone-like subgroup within the FGF superfamily. The members of this subfamily, FGF19, FGF21 and FGF23, are characterized by their reduced binding affinity for heparin that enables them to be transported in the circulation and function in an endocrine manner. It is likely that FGF21 also acts in an autocrine and paracrine fashion, as multiple organs can produce this protein and its plasma concentration seems to be below the level necessary to induce a pharmacological effect. FGF21 signals via FGF receptors, but for efficient receptor engagement it requires a cofactor, membrane-spanning bKlotho (KLB). The regulation of glucose uptake in adipocytes was the initial biological activity ascribed to FGF21, but this hormone is now recognized to stimulate many other pathways in vitro and display multiple pharmacological effects in metabolically compromised animals and humans. Understanding of the precise physiology of FGF21 and its potential medicinal role has evolved exponentially over the last decade, yet numerous aspects remain to be defined and others are a source of debate. Here we provide a historical overview of the advances in FGF21 biology focusing on the uncertainties in the mechanism of action as well as the differing viewpoints relating to this intriguing protein.

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Section: Fgf21 and Lipolysismentioning

confidence: 57%

Fibroblast growth factor 21 night watch: advances and uncertainties in the field

Kharitonenkov

DiMarchi

2016

J Intern Med

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“…However, clinical trials have shown that, although the promising glucose‐lowering effects observed in studies using rodents did not translate to humans, FGF21 agonism did lead to a decrease in serum TG levels . Such an effect was also observed in a recent study, demonstrating that Fgf21 administration in mice‐reduced VLDL secretion while also increasing TG‐rich lipoprotein catabolism . Fibroblast growth factor 21 has also demonstrated an ability to reduce body weight, insulin levels, and low‐density lipoprotein (LDL) cholesterol, while also increasing high‐density lipoprotein (HDL) levels in obese human subjects, although the underlying mechanism is not fully known at this time.…”

Section: Transcription Factors Important In Regulating Triglyceride Mmentioning

confidence: 97%

“…Phosphorylation of Pparα protein is essential for its transactivation, suggesting an increase in Pparα transcriptional activity, which is supported by the induction of Pparα target genes involved in fatty acid catabolism, including acyl CoA synthetase long‐chain family member 1 ( Acsl1 ), fatty acid binding protein 1 ( Fabp1 ), carnitine palmitoyltransferase 1a ( Cpt1a ), acyl‐Coenzyme A dehydrogenase, medium chain ( Acadm ), and 3‐hydroxy‐3‐methylglutaryl‐CoA synthase 2 (mitochondrial) ( Hmgcs2 ) . Additionally, expression of Fgf21, an important Pparα target that may reduce TG levels via increased TG‐rich lipoprotein catabolism, demonstrated an 8‐fold increase in gene expression and a 7‐fold increase in serum protein levels . Such changes in gene and protein expression were accompanied by a 28% decrease in serum TG levels.…”

Section: Grape Seed Procyanidin Extractmentioning

confidence: 99%

Mechanistic insight into nuclear receptor‐mediated regulation of bile acid metabolism and lipid homeostasis by grape seed procyanidin extract (GSPE)

Downing

Edgar

Ellison

et al. 2017

Cell Biochemistry & Function

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Dietary procyanidins have emerged as important bioactive components that regulate various metabolic pathways to maintain homeostasis. Grape seed procyanidin extract (GSPE), in particular, has demonstrated regulatory effects on bile acid and lipid metabolism in vivo. While numerous studies in rodent models have shown the potent hypolipidemic action of grape seed extracts, human studies have shown inconsistent results. This review will focus on the molecular mechanisms underlying the hypolipidemic actions of GSPE identified to date, specifically highlighting the effects exerted via nuclear receptors. Such evidence may provide avenues for future research in human subjects with GSPE as a therapeutic treatment for the prevention and amelioration of the metabolic syndrome and cardiovascular disease.

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“…In type 2 diabetes, FGF21 decreases body weight and improves the lipid profile (Gaich et al , ; Talukdar et al , ). In obese type 2 diabetic mice, FGF21 lowers plasma triglycerides by lipoprotein catabolism in adipose tissue and maintains adipocyte phospholipid homeostasis (Foltz et al , ; Schlein et al , ; Ye et al , ; Stanislaus et al , ). FGF21 also increases lipid use in response to amino acid starvation (De Sousa‐Coelho et al , ).…”

Section: Potential Therapeutic Targetsmentioning

confidence: 99%

Dyslipidemia in retinal metabolic disorders

Chen

Cagnone

et al. 2019

EMBO Mol Med

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The light‐sensitive photoreceptors in the retina are extremely metabolically demanding and have the highest density of mitochondria of any cell in the body. Both physiological and pathological retinal vascular growth and regression are controlled by photoreceptor energy demands. It is critical to understand the energy demands of photoreceptors and fuel sources supplying them to understand neurovascular diseases. Retinas are very rich in lipids, which are continuously recycled as lipid‐rich photoreceptor outer segments are shed and reformed and dietary intake of lipids modulates retinal lipid composition. Lipids (as well as glucose) are fuel substrates for photoreceptor mitochondria. Dyslipidemia contributes to the development and progression of retinal dysfunction in many eye diseases. Here, we review photoreceptor energy demands with a focus on lipid metabolism in retinal neurovascular disorders.

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FGF21 lowers plasma triglycerides by accelerating lipoprotein catabolism in white and brown adipose tissues

Cited by 9 publications

References 0 publications

Fibroblast growth factor 21 night watch: advances and uncertainties in the field

Fibroblast growth factor 21 night watch: advances and uncertainties in the field

Mechanistic insight into nuclear receptor‐mediated regulation of bile acid metabolism and lipid homeostasis by grape seed procyanidin extract (GSPE)

Dyslipidemia in retinal metabolic disorders

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