Fibroblast Growth Factor 21 Reduces the Severity of Cerulein-Induced Pancreatitis in Mice

Johnson, C. L.; Weston, Jacqueline Y.; Chadi, Sami A.; Fazio, Elena N.; Huff, Murray W.; Kharitonenkov, Alexei; Köester, Anja; Pin, Christopher L.

doi:10.1053/j.gastro.2009.07.064

Cited by 150 publications

(154 citation statements)

References 34 publications

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“…Tissue protein extraction, protein electrophoresis, and immunoblotting were performed as described (23). Antibodies used were rabbit anti-CPA (1:2,000; AbD Serotec, Oxford, UK) or goat anti-FGF21 (1:500; R&D Systems, Minneapolis, MN).…”

Section: Methodsmentioning

confidence: 99%

“…We have shown that FGF21 is increased in the pancreas during ceruleininduced pancreatitis (CIP) and L-arginine induced pancreatitis and can target pancreatic acinar cells in culture (23). Overexpressing FGF21 reduces the severity of CIP, and Fgf21 Ϫ/Ϫ mice showed enhanced inflammation and fibrosis during CIP, highlighting a protective role for FGF21 in restricting injury during pancreatitis (23). However, there are still limited data regarding the regulation and function of FGF21 in the exocrine pancreas in vivo.…”

mentioning

confidence: 99%

“…FGF21 expression and secretion are triggered by a number of adverse environmental events including fasting (13), alterations in diet leading to increased fatty acid oxidation (4), obesity (9), or hypothermia (14). We have shown that FGF21 is increased in the pancreas during ceruleininduced pancreatitis (CIP) and L-arginine induced pancreatitis and can target pancreatic acinar cells in culture (23). Overexpressing FGF21 reduces the severity of CIP, and Fgf21 Ϫ/Ϫ mice showed enhanced inflammation and fibrosis during CIP, highlighting a protective role for FGF21 in restricting injury during pancreatitis (23).…”

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confidence: 99%

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Silencing of the Fibroblast growth factor 21 gene is an underlying cause of acinar cell injury in mice lacking MIST1

Johnson

Mehmood

Laing

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Silencing of the Fibroblast growth factor 21 gene is an underlying cause of acinar cell injury in mice lacking MIST1

Johnson

Mehmood

Laing

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

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“…Systemic administration and transgenic overexpression of this factor leads to weight loss in obese mouse models through increases in energy expenditure without alterations in food intake (Kharitonenkov et al 2005;Coskun et al 2008). Thus far, the known target tissues of FGF21 action are liver, epididymal WAT (Fisher et al 2010), and the pancreas (Wente et al 2006;Johnson et al 2009). The hepatic effects of FGF21 are dramatic, leading to increased fatty acid oxidation (Coskun et al 2008;Potthoff et al 2009).…”

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confidence: 99%

FGF21 regulates PGC-1α and browning of white adipose tissues in adaptive thermogenesis

Fisher¹,

Kleiner²,

Douris³

et al. 2012

Genes Dev.

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Certain white adipose tissue (WAT) depots are readily able to convert to a ''brown-like'' state with prolonged cold exposure or exposure to b-adrenergic compounds. This process is characterized by the appearance of pockets of uncoupling protein 1 (UCP1)-positive, multilocular adipocytes and serves to increase the thermogenic capacity of the organism. We show here that fibroblast growth factor 21 (FGF21) plays a physiologic role in this thermogenic recruitment of WATs. In fact, mice deficient in FGF21 display an impaired ability to adapt to chronic cold exposure, with diminished browning of WAT. Adipose-derived FGF21 acts in an autocrine/paracrine manner to increase expression of UCP1 and other thermogenic genes in fat tissues. FGF21 regulates this process, at least in part, by enhancing adipose tissue PGC-1a protein levels independently of mRNA expression. We conclude that FGF21 acts to activate and expand the thermogenic machinery in vivo to provide a robust defense against hypothermia.

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“…FGF21 is highly expressed in the pancreas and has protective effects against cerulein-induced pancreatitis [63]. Supporting data show that FGF21-deficient mice are more susceptible to damage, and FGF21-overexpressing mice are partly protected.…”

Section: Pancreas: Fgf21 Preserves B-cell Functionmentioning

confidence: 57%

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

Pérez-Martí

Sandoval

Marrero

et al. 2016

Hormone Molecular Biology and Clinical Investigation

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Abstract:Obesity 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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Fibroblast Growth Factor 21 Reduces the Severity of Cerulein-Induced Pancreatitis in Mice

Cited by 150 publications

References 34 publications

Silencing of the Fibroblast growth factor 21 gene is an underlying cause of acinar cell injury in mice lacking MIST1

Silencing of the Fibroblast growth factor 21 gene is an underlying cause of acinar cell injury in mice lacking MIST1

FGF21 regulates PGC-1α and browning of white adipose tissues in adaptive thermogenesis

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

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