Anti-inflammatory effects of exercise training in adipose tissue do not require FGF21

Porter, Jay W.; Rowles, Joe L.; Fletcher, Justin A.; Zidon, Terese M.; Winn, Nathan C.; McCabe, Leighton; Park, Young Min; Perfield, James W.; Thyfault, John P.; Rector, R. Scott; Padilla, Jaume; Vieira‐Potter, Victoria J.

doi:10.1530/joe-17-0190

Cited by 25 publications

(33 citation statements)

References 57 publications

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“…MR significantly reduced expression of Ccl2 , Itgam , and Itgax in liver and Ccl2 , Adgre1 , Itgam , and Itgax in adipose tissue of Fgf21 ‐/‐ mice (Figure ). These findings are in line with a previous study that reported that although exercise both increased FGF21 and reduced inflammation, FGF21 was not required for the exercise‐induced reduction in inflammation in adipose tissue . As previously reported , MR produced an unexpected reduction in food intake in the Fgf21 ‐/‐ mice.…”

Section: Discussionsupporting

confidence: 93%

“…The greater expression of these genes indicates that Fgf21 ‐/‐ mice are not only more susceptible to HFD‐induced inflammation but are also likely at greater risk for insulin resistance. Indeed, Fgf21 ‐/‐ mice were shown to have greater adipose tissue inflammation and insulin resistance compared with WT mice . Similarly, others showed that Fgf21 ‐/‐ mice had elevated levels of inflammation in pancreas when fed a HFD compared with WT mice .…”

Section: Discussionmentioning

confidence: 98%

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Dietary Methionine Restriction Reduces Inflammation Independent of FGF21 Action

Sharma

Dixon

Jung

et al. 2019

Obesity

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Objective: Methionine restriction (MR) decreases inflammation and improves markers of metabolic disease in rodents. MR also increases hepatic and circulating concentrations of fibroblast growth factor 21 (FGF21). Emerging evidence has suggested that FGF21 exerts anti-inflammatory effects. The purpose of this study was to determine the role of FGF21 in mediating the MR-induced reduction in inflammation. Methods: Wild-type and Fgf21 -/mice were fed a high-fat (HF) control or HF-MR diet for 8 weeks. In a separate experiment, mice were fed a HF diet (HFD) for 10 weeks. Vehicle or recombinant FGF21 (13.6 µg/d) was administered via osmotic minipump for an additional 2 weeks. Inflammation and metabolic parameters were measured. Results: Fgf21 -/mice were more susceptible to HFD-induced inflammation, and MR reduced inflammation in white adipose tissue (WAT) and liver of Fgf21 -/mice. MR downregulated activity of signal transducer and activator of transcription 3 in WAT of both genotypes. FGF21 administration reduced hepatic lipids and blood glucose concentrations. However, there was little effect of FGF21 on inflammatory gene expression in liver or adipose tissue or circulating cytokines. Conclusions: MR reduces inflammation independent of FGF21 action. Endogenous FGF21 is important to protect against the development of HFD-induced inflammation in liver and WAT, yet administration of lowdose FGF21 has little effect on markers of inflammation.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 98%

Dietary Methionine Restriction Reduces Inflammation Independent of FGF21 Action

Sharma

Dixon

Jung

et al. 2019

Obesity

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“…One possible reason is that the higher levels of circulating FGF21 in pregnant women with GDM could be a compensatory response to the underlying differences in maternal physiology such as higher insulin resistance at the start of the pregnancy, poor reserve in insulin secretion capacity, and low-level inflammation in GDM subjects [27][28][29]. Additionally, circulating FGF21 levels are associated with overeating [30]; hence, increased food intake during pregnancy might also contribute to higher FGF21 levels in GDM subjects. Besides, increased FGF21 levels could reduce the appetite for sugar and preference for carbohydrate, and promote protein ingestion [31,32], thereby ensuring the supply of sufficient essential nutrients during pregnancy.…”

Section: Discussionmentioning

confidence: 99%

Circulating levels of fibroblast growth factor 21 in gestational diabetes mellitus: a meta-analysis

et al. 2021

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In recent times, the role of fibroblast growth factor 21 (FGF21) in patients with gestational diabetes mellitus (GDM) has been increasingly investigated. However, to our knowledge, no systematic analysis has been conducted yet to evaluate the relationship between FGF21 levels and GDM. Confirmed studies related to circulating FGF21 levels and GDM were searched from the databases of PubMed, ISI Web of Science, MEDLINE and EMBASE. Data were reported as standard mean difference (SMD) and associated 95% confidence intervals (CIs). Analysis were performed with Review Manager 5.2 and Stata version 11.0. A total of 392 cases and 435 controls in nine articles were included in this meta-analysis. The circulating FGF21 levels in pregnant women with GDM was higher than that in controls (random effects MD [95% CI] = 0.46, [0.07-0.86], p = 0.02). The result of multivariate meta-regression showed that sample size and point of sample collection contributed to heterogeneity (p = 0.033 and p = 0.047, respectively). Additionally, the results showed that there was no publication bias in this meta-analysis (Z = 1.36, p = 0.175; t = 1.24, p = 0.256, respectively). To conclude, this meta-analysis provides evidence that circulating FGF21 levels are higher in GDM subjects than controls, and it is important to clarify the relationship between circulating FGF21 levels and pregnant women with GDM in accurate prediction of GDM.

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“…However, voluntary wheel running reduced adiposity, adipose tissue inflammation, hyperinsulinemia, and hepatic fatty acid content and oxidation in both FGF21 KO mice and their control littermates (44,129). On the contrary, in mice fed with a high fat diet (HFD), voluntary wheel running did not improve hepatic triglyceride content and glucose tolerance but prevented weight and fat mass gain independently of genotype (97).…”

Section: Moreover In Cultured Skeletal Muscle Cells Fgf21 Expressiomentioning

confidence: 98%

Role of exercise-induced hepatokines in metabolic disorders

Ennequin

Sirvent

Whitham

2019

American Journal of Physiology-Endocrinology and Metabolism

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The health-promoting effects of physical activity to prevent and treat metabolic disorders are numerous. However, the underlying molecular mechanisms are not yet completely deciphered. In recent years, studies have referred to the liver as an endocrine organ, since it releases specific proteins called hepatokines. Some of these hepatokines are involved in whole body metabolic homeostasis and are theorized to participate in the development of metabolic disease. In this regard, the present review describes the role of Fibroblast Growth Factor 21, Fetuin-A, Angiopoietin-like protein 4, and Follistatin in metabolic disease and their production in response to acute exercise. Also, we discuss the potential role of hepatokines in mediating the beneficial effects of regular exercise and the future challenges to the discovery of new exercise-induced hepatokines.

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Anti-inflammatory effects of exercise training in adipose tissue do not require FGF21

Cited by 25 publications

References 57 publications

Dietary Methionine Restriction Reduces Inflammation Independent of FGF21 Action

Dietary Methionine Restriction Reduces Inflammation Independent of FGF21 Action

Circulating levels of fibroblast growth factor 21 in gestational diabetes mellitus: a meta-analysis

Role of exercise-induced hepatokines in metabolic disorders

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