Faculty Opinions recommendation of Hepatic fibroblast growth factor 21 is regulated by PPARalpha and is a key mediator of hepatic lipid metabolism in ketotic states.

Fibroblast growth factor 21 (FGF21) is a metabolic regulator of energy and lipid metabolism. FGF21 is highly expressed in liver while FGF21 receptors (beta-klotho (KLB) and FGFR1c) are highly expressed in white adipose tissues (WATs). Plasma FGF21 has been shown to be increased after 7–10 days of fasting but oppositely plasma FGF21 is also increased in obesity. The aim of this study was to measure the effect of 60 h of fasting on plasma FGF21 levels in obese and lean subjects and to determine the gene expression of KLB and FGFR1c in the subcutaneous WAT before, during and after 60 h of fasting. Eight obese (BMI >30 kg/m2) and seven lean subjects (BMI <25 kg/m2) were fasted for 60 h and blood samples were taken at time 0 and after 12, 36 and 60 h of fasting. A biopsy from the subcutaneous WAT was taken at time 0, 12 and 60 h of fasting. FGF21 was measured in plasma by an ELISA and mRNA expression of KLB and FGFR1c was measured in WAT by quantitative PCR (qPCR). The fast significantly decreased plasma FGF21 in obese subjects while no change in plasma FGF21 was observed in lean subjects. Interestingly, KLB was significantly decreased in WAT in response to fasting in both lean and obese subjects indicating a potential important adaptive regulation of KLB in response to fasting.

Download Full-text

Fibroblast growth factor 21: a regulator of metabolic disease and health span

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00101.2017 ◽

2017 ◽

Vol 313 (3) ◽

pp. E292-E302 ◽

Cited By ~ 32

Author(s):

Ting Xie ◽

Po Sing Leung

Keyword(s):

Lipid Metabolism ◽

Growth Factor ◽

Fibroblast Growth Factor ◽

Metabolic Diseases ◽

Scientific Basis ◽

Fibroblast Growth Factor 21 ◽

Fibroblast Growth ◽

Glucose And Lipid Metabolism ◽

Care Guidelines

Fibroblast growth factor 21 (FGF21) is a potent endocrine regulator with physiological effects on glucose and lipid metabolism and thus garners much attention for its translational potential for the management of obesity and related metabolic syndromes. FGF21 is mainly expressed in several metabolically active tissue organs, such as the liver, adipose tissue, skeletal muscle, and pancreas, with profound effects and therapeutic relevance. Emerging experimental and clinical data point to the demonstrated metabolic benefits of FGF21, which include, but are not limited to, weight loss, glucose and lipid metabolism, and insulin sensitivity. In addition, FGF21 also acts directly through its coreceptor β-klotho in the brain to alter light-dark cycle activity. In this review, we critically appraise current advances in understanding the physiological actions of FGF21 and its role as a biomarker of various metabolic diseases, especially type 2 diabetes mellitus. We also discuss the potentially exciting role of FGF21 in improving our health and prolonging our life span. This information will provide a fuller understanding for further research into FGF21, as well as providing a scientific basis for potentially establishing health care guidelines for this promising molecule.

Download Full-text

Rapid increase in fibroblast growth factor 21 in protein malnutrition and its impact on growth and lipid metabolism – ERRATUM

British Journal Of Nutrition ◽

10.1017/s0007114515003955 ◽

2015 ◽

Vol 114 (9) ◽

pp. 1535-1536 ◽

Cited By ~ 2

Author(s):

Yori Ozaki ◽

Kenji Saito ◽

Kyoko Nakazawa ◽

Morichika Konishi ◽

Nobuyuki Itoh ◽

...

Keyword(s):

Lipid Metabolism ◽

Growth Factor ◽

Fibroblast Growth Factor ◽

Protein Malnutrition ◽

Fibroblast Growth Factor 21 ◽

Fibroblast Growth

Download Full-text

Dual effects of fibroblast growth factor 21 on hepatic energy metabolism

Journal of Endocrinology ◽

10.1530/joe-15-0334 ◽

2015 ◽

Vol 227 (1) ◽

pp. 37-47 ◽

Cited By ~ 11

Author(s):

Ricardo J Samms ◽

Michelle Murphy ◽

Maxine J Fowler ◽

Scott Cooper ◽

Paul Emmerson ◽

...

Keyword(s):

Energy Metabolism ◽

Growth Factor ◽

Fibroblast Growth Factor ◽

Lipid Content ◽

Negative Regulator ◽

Fibroblast Growth Factor 21 ◽

Fibroblast Growth ◽

Hepatic Lipid ◽

Siberian Hamsters ◽

Hepatic Lipid Content

The aim of this study was to investigate the mechanisms by which fibroblast growth factor 21 (FGF21) affects hepatic integration of carbohydrate and fat metabolism in Siberian hamsters, a natural model of adiposity. Twelve aged matched adult male Siberian hamsters maintained in their long-day fat state since birth were randomly assigned to one of two treatment groups and were continuously infused with either vehicle (saline;n=6) or recombinant human FGF21 protein (1 mg/kg per day;n=6) for 14 days. FGF21 administration caused a 40% suppression (P<0.05) of hepatic pyruvate dehydrogenase complex (PDC), the rate-limiting step in glucose oxidation, a 34% decrease (P<0.05) in hepatic acetylcarnitine accumulation, an index of reduced PDC flux, a 35% increase (P<0.05) in long-chain acylcarnitine content (an index of flux through β-oxidation) and a 47% reduction (P<0.05) in hepatic lipid content. These effects were underpinned by increased protein abundance of PD kinase-4 (PDK4, a negative regulator of PDC), the phosphorylated (inhibited) form of acetyl-CoA carboxylase (ACC, a negative regulator of delivery of fatty acids into the mitochondria) and the transcriptional co-regulators of energy metabolism peroxisome proliferator activated receptor gamma co-activator alpha (PGC1α) and sirtuin-1. These findings provide novel mechanistic basis to support the notion that FGF21 exerts profound metabolic benefits in the liver by modulating nutrient flux through both carbohydrate (mediated by a PDK4-mediated suppression of PDC activity) and fat (mediated by deactivation of ACC) metabolism, and therefore may be an attractive target for protection from increased hepatic lipid content and insulin resistance that frequently accompany obesity and diabetes.

Download Full-text