Recombinant murine fibroblast growth factor 21 ameliorates obesity-related inflammation in monosodium glutamate-induced obesity rats

Wang, Wen-Fei; Li, Siming; Ren, Guangxin; Zheng, Wu; Lu, Yujia; Yu, Yin-Hang; Xu, Wenjuan; Li, Tian-He; Zhou, Lihong; Liu, Yan; Li, Deshan

doi:10.1007/s12020-014-0433-5

Cited by 50 publications

(45 citation statements)

References 30 publications

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“…The administration of recombinant FGF21 to streptozotocin-treated mice dosedependently repressed FGF21 gene expression in the liver to a greater extent than streptozotocin alone [41]. In a separate study, FGF21 transcript levels were substantially lowered in the liver following FGF21 administration [42]. These results suggest the presence of a negative feedback by FGF21 directed at its own expression.…”

Section: Body Of Review Regulation By Starvation and Overnutritionmentioning

confidence: 83%

The regulation of FGF21 gene expression by metabolic factors and nutrients

Erickson

Moreau

2016

Hormone Molecular Biology and Clinical Investigation

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Fibroblast growth factor 21 (FGF21) gene expression is altered by a wide array of physiological, metabolic, and environmental factors. Among dietary factors, high dextrose, low protein, methionine restriction, short-chain fatty acids (butyric acid and lipoic acid), and all-trans-retinoic acid were repeatedly shown to induce FGF21 expression and circulating levels. These effects are usually more pronounced in liver or isolated hepatocytes than in adipose tissue or isolated fat cells. Although peroxisome proliferator-activated receptor α (PPARα) is a key mediator of hepatic FGF21 expression and function, including the regulation of gluconeogenesis, ketogenesis, torpor, and growth inhibition, there is increasing evidence of PPARα-independent transactivation of the FGF21 gene by dietary molecules. FGF21 expression is believed to follow the circadian rhythm and be placed under the control of first order clock-controlled transcription factors, retinoic acid receptor-related orphan receptors (RORs) and nuclear receptors subfamily 1 group D (REV-ERBs), with FGF21 rhythm being anti-phase to REV-ERBs. Key metabolic hormones such as glucagon, insulin, and thyroid hormone have presumed or clearly demonstrated roles in regulating FGF21 transcription and secretion. The control of the FGF21 gene by glucagon and insulin appears more complex than first anticipated. Some discrepancies are noted and will need continued studies. The complexity in assessing the significance of FGF21 gene expression resides in the difficulty to ascertain (i) when transcription results in local or systemic increase of FGF21 protein; (ii) if FGF21 is among the first or second order genes upregulated by physiological, metabolic, and environmental stimuli, or merely an epiphenomenon; and (iii) whether FGF21 may have some adverse effects alongside beneficial outcomes.

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Section: Body Of Review Regulation By Starvation and Overnutritionmentioning

confidence: 83%

The regulation of FGF21 gene expression by metabolic factors and nutrients

Erickson

Moreau

2016

Hormone Molecular Biology and Clinical Investigation

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“…FGF21 is also secreted into circulation as a myokine in Cpt1b m−/− mice and promotes browning of inguinal white adipose tissue (iWAT), but not eWAT in Cpt1b m−/− mice24. Recent reports have shown that FGF21 decreased expression of IL6 and TNFα in adipose tissue of obese rats and suppressed inflammation in mouse models with FA-induced or diabetic renal dysfunction6465. Thus muscle derived FGF21 in Cpt1b m−/− mice could have anti-inflammatory action locally in the presence of intracellular toxic lipids, and on adipose or possibly other tissues by circulation contributing to the improvement in inflammatory status at the face of constantly elevated systemic lipids.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial fat oxidation is essential for lipid-induced inflammation in skeletal muscle in mice

Warfel

Bermudez

Mendoza

et al. 2016

Sci Rep

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Inflammation, lipotoxicity and mitochondrial dysfunction have been implicated in the pathogenesis of obesity-induced insulin resistance and type 2 diabetes. However, how these factors are intertwined in the development of obesity/insulin resistance remains unclear. Here, we examine the role of mitochondrial fat oxidation on lipid-induced inflammation in skeletal muscle. We used skeletal muscle-specific Cpt1b knockout mouse model where the inhibition of mitochondrial fatty acid oxidation results in accumulation of lipid metabolites in muscle and elevated circulating free fatty acids. Gene expression of pro-inflammatory cytokines, chemokines, and cytokine- and members of TLR-signalling pathways were decreased in Cpt1bm−/− muscle. Inflammatory signalling pathways were not activated when evaluated by multiplex and immunoblot analysis. In addition, the inflammatory response to fatty acids was reduced in primary muscle cells derived from Cpt1bm−/− mice. Gene expression of Cd11c, the M1 macrophage marker, was decreased; while Cd206, the M2 macrophage marker, was increased in skeletal muscle of Cpt1bm−/− mice. Finally, expression of pro-inflammatory markers was decreased in white adipose tissue of Cpt1bm−/− mice. We show that the inflammatory response elicited by elevated intracellular lipids in skeletal muscle is repressed in Cpt1bm−/− mice, strongly supporting the hypothesis that mitochondrial processing of fatty acids is essential for the lipid-induction of inflammation in muscle.

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“…As a result, rats treated with MSG at the neonatal period developed hypophagia, accompanied by arrest in the body weight gain, and concomitant enhanced basal levels of all HPA axis components and leptin (Perello et al 2003;Quines et al 2014). This longterm deregulation in the energy homeostasis induced several metabolic alterations (Poletto et al 2015;Wang et al 2015).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, it has been demonstrated that MSG administration induces alterations in glucose transporters (GLUT) in the liver, muscle and fat and this is associated with hyperglycemia and insulin resistance present in these animals (Nardeli et al 2011;Leguisamo et al 2012;Poletto et al 2015;Wang et al 2015). Furthermore, the MSGtreated rats develop hepatic steatosis in adulthood and an increase in the activities of ATPase enzymes in the liver, accompanied by an increase in the state III of mitochondrial respiration (Lazarin et al 2011;Oliveira et al 2011;Wang et al 2015).…”

Section: Introductionmentioning

confidence: 99%

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Homeostatic effect of p-chloro-diphenyl diselenide on glucose metabolism and mitochondrial function alterations induced by monosodium glutamate administration to rats

et al. 2015

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The metabolic syndrome is a group of metabolic alterations considered a worldwide public health problem. Organic selenium compounds have been reported to have many different pharmacological actions, such as anti-hypercholesterolemic and anti-hyperglycemic. The aim of this study was to evaluate the effect of p-chloro-diphenyl diselenide (p-ClPhSe)2, an organic selenium compound, in a model of obesity induced by monosodium glutamate (MSG) administration in rats. The rats were treated during the first ten postnatal days with MSG and received (p-ClPhSe)2 (10 mg/kg, intragastrically) from 45th to 51 th postnatal day. Glucose, lipid and lactate levels were determined in plasma of rats. Glycogen levels and activities of tyrosine aminotransferase, hexokinase, citrate synthase and glucose-6-phosphatase (G-6-Pase) were determined in livers of rats. Renal G-6-Pase activity was also determined. The purine content [Adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine monophosphate] and mitochondrial functionality in the liver were also investigated. p-(ClPhSe)2 did not alter the reduction in growth performance and in the body weight caused by MSG but reduced epididymal fat deposition of rats. p-(ClPhSe)2 restored glycemia, triglycerides, cholesterol and lactate levels as well as the glucose metabolism altered in rats treated with MSG. p-(ClPhSe)2 restored hepatic mitochondrial dysfunction and the decrease in citrate synthase activity and ATP and ADP levels caused by MSG in rats. In summary, (p-ClPhSe)2 had homeostatic effects on glucose metabolism and mitochondrial function alterations induced by MSG administration to rats.

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Recombinant murine fibroblast growth factor 21 ameliorates obesity-related inflammation in monosodium glutamate-induced obesity rats

Cited by 50 publications

References 30 publications

The regulation of FGF21 gene expression by metabolic factors and nutrients

The regulation of FGF21 gene expression by metabolic factors and nutrients

Mitochondrial fat oxidation is essential for lipid-induced inflammation in skeletal muscle in mice

Homeostatic effect of p-chloro-diphenyl diselenide on glucose metabolism and mitochondrial function alterations induced by monosodium glutamate administration to rats

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