Fibroblast growth factor 21 analogue LY2405319 lowers blood glucose in streptozotocin-induced insulin-deficient diabetic mice by restoring brown adipose tissue function

2014 ◽  
Vol 17 (2) ◽  
pp. 161-169 ◽  
Author(s):  
J.-H. Kim ◽  
K.-H. Bae ◽  
Y.-K. Choi ◽  
Y. Go ◽  
M. Choe ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Blood Glucose ◽  
Growth Factor ◽  
Brown Adipose Tissue ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Diabetic Mice ◽  
Brown Adipose

scholarly journals Fibroblast Growth Factor-21, Leptin, and Adiponectin Responses to Acute Cold-Induced Brown Adipose Tissue Activation

2020 ◽  
Vol 105 (3) ◽  
pp. e520-e531 ◽  
Author(s):  
Lijuan Sun ◽  
Jianhua Yan ◽  
Hui Jen Goh ◽  
Priya Govindharajulu ◽  
Sanjay Verma ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Growth Factor ◽  
Brown Adipose Tissue ◽  
Fibroblast Growth Factor ◽  
Cold Exposure ◽  
Maximum Temperature ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Adiponectin Concentration ◽  
Brown Adipose

Abstract Background Adipocyte-derived hormones play a role in insulin sensitivity and energy homeostasis. However, the relationship between circulating fibroblast growth factor 21 (FGF21), adipocytokines and cold-induced supraclavicular brown adipose tissue (sBAT) activation is underexplored. Objective Our study aimed to investigate the relationships between cold-induced sBAT activity and plasma FGF21 and adipocytokines levels in healthy adults. Design Nineteen healthy participants underwent energy expenditure (EE) and supraclavicular infrared thermography (IRT) within a whole-body calorimeter at baseline and at 2 hours post-cold exposure. 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/magnetic resonance (PET/MR) imaging scans were performed post-cold exposure. PET sBAT mean standardized uptake value (SUV mean), MR supraclavicular fat fraction (sFF), anterior supraclavicular maximum temperature (Tscv max) and EE change (%) after cold exposure were used to quantify sBAT activity. Main Outcome Measures Plasma FGF21, leptin, adiponectin, and tumor necrosis factor alpha (TNFα) at baseline and 2 hours post-cold exposure. Body composition at baseline by dual-energy x-ray absorptiometry (DXA). Results Plasma FGF21 and adiponectin levels were significantly reduced after cold exposure in BAT-positive subjects but not in BAT-negative subjects. Leptin concentration was significantly reduced in both BAT-positive and BAT-negative participants after cold exposure. Adiponectin concentration at baseline was positively strongly associated with sBAT PET SUV mean (coefficient, 3269; P = 0.01) and IRT Tscv max (coefficient, 6801; P  = 0.03), and inversely correlated with MR sFF (coefficient, −404; P  = 0.02) after cold exposure in BAT-positive subjects but not in BAT-negative subjects. Conclusion Higher adiponectin concentrations at baseline indicate a greater cold-induced sBAT activity, which may be a novel predictor for sBAT activity in healthy BAT-positive adults. Highlights A higher adiponectin concentration at baseline was associated with higher cold-induced supraclavicular BAT PET SUV mean and IRT Tscv max, and lower MR supraclavicular FF. Adiponectin levels maybe a novel predictor for cold-induced sBAT activity.

Fibroblast growth factor-21 is expressed in neonatal and pheochromocytoma-induced adult human brown adipose tissue

Metabolism ◽  
2014 ◽  
Vol 63 (3) ◽  
pp. 312-317 ◽  
Author(s):  
Elayne Hondares ◽  
José M. Gallego-Escuredo ◽  
Pavel Flachs ◽  
Andrea Frontini ◽  
Ruben Cereijo ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Growth Factor ◽  
Brown Adipose Tissue ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Adult Human ◽  
Brown Adipose

scholarly journals Inducible Loss of the Aryl Hydrocarbon Receptor Activates Perigonadal White Fat Respiration and Brown Fat Thermogenesis via Fibroblast Growth Factor 21

2019 ◽  
Vol 20 (4) ◽  
pp. 950 ◽  
Author(s):  
Nathaniel Girer ◽  
Dwayne Carter ◽  
Nisha Bhattarai ◽  
Mehnaz Mustafa ◽  
Larry Denner ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Growth Factor ◽  
Aryl Hydrocarbon Receptor ◽  
Fibroblast Growth Factor ◽  
Knockout Mouse ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Knockout Mouse Model ◽  
Aryl Hydrocarbon ◽  
Brown Adipose

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor highly expressed in hepatocytes. Researchers have employed global and liver-specific conditional Ahr knockout mouse models to characterize the physiological roles of the AHR; however, the gestational timing of AHR loss in these models can complicate efforts to distinguish the direct and indirect effects of post-gestational AHR deficiency. Utilizing a novel tamoxifen-inducible AHR knockout mouse model, we analyzed the effects of hepatocyte-targeted AHR loss in adult mice. The data demonstrate that AHR deficiency significantly reduces weight gain and adiposity, and increases multilocular lipid droplet formation within perigonadal white adipose tissue (gWAT). Protein and mRNA expression of fibroblast growth factor 21 (FGF21), an important hepatokine that activates thermogenesis in brown adipose tissue (BAT) and gWAT, significantly increases upon AHR loss and correlates with a significant increase of BAT and gWAT respiratory capacity. Confirming the role of FGF21 in mediating these effects, this phenotype is reversed in mice concomitantly lacking AHR and FGF21 expression. Chromatin immunoprecipitation analyses suggest that the AHR may constitutively suppress Fgf21 transcription through binding to a newly identified xenobiotic response element within the Fgf21 promoter. The data demonstrate an important AHR-FGF21 regulatory axis that influences adipose biology and may represent a “druggable” therapeutic target for obesity and its related metabolic disorders.

Fibroblast Growth Factor-9 Regulates Adaptive Brown Adipose Tissue Mass Expansion

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 277-OR ◽  
Author(s):  
FARNAZ SHAMSI ◽  
TIAN LIAN HUANG ◽  
YU-HUA TSENG
Keyword(s):  
Adipose Tissue ◽  
Growth Factor ◽  
Brown Adipose Tissue ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth ◽  
Tissue Mass ◽  
Brown Adipose ◽  
Adipose Tissue Mass ◽  
Mass Expansion

scholarly journals Fibroblast Growth Factor 21 and Thyroid Hormone Show Mutual Regulatory Dependency but Have Independent Actions In Vivo

Endocrinology ◽  
2014 ◽  
Vol 155 (5) ◽  
pp. 2031-2040 ◽  
Author(s):  
Eleni M. Domouzoglou ◽  
ffolliott Martin Fisher ◽  
Inna Astapova ◽  
Elliott C. Fox ◽  
Alexei Kharitonenkov ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Growth Factor ◽  
Thyroid Hormone ◽  
Fibroblast Growth Factor ◽  
Knockout Mice ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Brown Adipose ◽  
Circulating Levels

Thyroid hormone (TH) regulates fibroblast growth factor 21 (FGF21) levels in the liver and in the adipose tissue. In contrast, peripheral FGF21 administration leads to decreased circulating levels of TH. These data suggest that FGF21 and TH could interact to regulate metabolism. In the present study, we confirmed that TH regulates adipose and hepatic FGF21 expression and serum levels in mice. We next investigated the influence of TH administration on key serum metabolites, gene expression in the liver and brown adipose tissue, and energy expenditure in FGF21 knockout mice. Surprisingly, we did not observe any significant differences in the effects of TH on FGF21 knockout mice compared with those in wild-type animals, indicating that TH acts independently of FGF21 for the specific outcomes studied. Furthermore, exogenous FGF21 administration to hypothyroid mice led to similar changes in serum and liver lipid metabolites and gene expression in both hypothyroid and euthyroid mice. Thus, it appears that FGF21 and TH have similar actions to decrease serum and liver lipids despite having some divergent regulatory effects. Whereas TH leads to up-regulation in the liver and down-regulation in brown adipose tissue of genes involved in the lipid synthesis pathway (eg, fatty acid synthase (FASN) and SPOT14), FGF21 leads to the opposite changes in expression of these genes. In conclusion, TH and FGF21 act independently on the outcomes studied, despite their ability to regulate each other's circulating levels. Thus, TH and FGF21 may modulate the availability of each other in critical metabolic states.

scholarly journals Nutritional regulation of fibroblast growth factor 21: from macronutrients to bioactive dietary compounds

2016 ◽  
Vol 30 (1) ◽  
Author(s):  
Albert Pérez-Martí ◽  
Viviana Sandoval ◽  
Pedro F. Marrero ◽  
Diego Haro ◽  
Joana Relat
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Metabolic Effects ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Nutritional Regulation ◽  
Ketogenic Diets ◽  
Brown Adipose

AbstractObesity is a worldwide health problem mainly due to its associated comorbidities. Fibroblast growth factor 21 (FGF21) is a peptide hormone involved in metabolic homeostasis in healthy individuals and considered a promising therapeutic candidate for the treatment of obesity. FGF21 is predominantly produced by the liver but also by other tissues, such as white adipose tissue (WAT), brown adipose tissue (BAT), skeletal muscle, and pancreas in response to different stimuli such as cold and different nutritional challenges that include fasting, high-fat diets (HFDs), ketogenic diets, some amino acid-deficient diets, low protein diets, high carbohydrate diets or specific dietary bioactive compounds. Its target tissues are essentially WAT, BAT, skeletal muscle, heart and brain. The effects of FGF21 in extra hepatic tissues occur through the fibroblast growth factor receptor (FGFR)-1c together with the co-receptor β-klotho (KLB). Mechanistically, FGF21 interacts directly with the extracellular domain of the membrane bound cofactor KLB in the FGF21- KLB-FGFR complex to activate FGFR substrate 2α and ERK1/2 phosphorylation. Mice lacking KLB are resistant to both acute and chronic effects of FGF21. Moreover, the acute insulin sensitizing effects of FGF21 are also absent in mice with specific deletion of adipose KLB or FGFR1. Most of the data show that pharmacological administration of FGF21 has metabolic beneficial effects. The objective of this review is to compile existing information about the mechanisms that could allow the control of endogenous FGF21 levels in order to obtain the beneficial metabolic effects of FGF21 by inducing its production instead of doing it by pharmacological administration.

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