Dataset Information

Dietary Methionine Restriction Reduces Inflammation Independent of FGF21 Action.

ABSTRACT:

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 low-dose FGF21 has little effect on markers of inflammation.

SUBMITTER: Sharma S

PROVIDER: S-EPMC6656589 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Publications

Dietary Methionine Restriction Reduces Inflammation Independent of FGF21 Action.

Sharma Shaligram S Dixon Taylor T Jung Sean S Graff Emily C EC Forney Laura A LA Gettys Thomas W TW Wanders Desiree D

Obesity (Silver Spring, Md.) 20190617 8

<h4>Objective</h4>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.<h4>Methods</h4>Wild-type and Fgf21<sup>-/-</sup> mice were fed a high-fat (HF) control ...[more]

PMID: 31207147

Similar Datasets

Project description:Continuous methionine restriction (MR) is one of only a few dietary interventions known to dramatically extend mammalian healthspan. For example, continuously methionine-restricted rodents show less age-related pathology and are up to 45% longer-lived than controls. Intriguingly, MR is feasible for humans, andanumberofstudieshavesuggestedthatmethionine-restrictedindividualsmayreceivesimilarhealthspan benefits as rodents. However, long-term adherence to a continuously methionine-restricted diet is likely to be challenging (or even undesirable) for many individuals. To address this, we previously developed an intermittent version of MR (IMR) and demonstrated that it confers nearly identical metabolic health benefits to mice as the continuous intervention, despite having a relatively short interventional period (i.e., only three days per week). We also observed that female mice undergoing IMR show a more pronounced amelioration of diet-induced dysglycemia than continuously methionine-restricted counterparts, while male mice undergoing IMR retain more lean body mass as compared with continuously methionine-restricted controls. Prompted by such findings, we sought to determine other ways in which IMR might compare favorably with continuous MR. While it is known that continuous MR has deleterious effects on bone in mice, including loss of both trabecular and cortical bone, we considered that mice undergoing IMR might retain more bone mass. Here, we report that, as compared with continuous MR, IMR results in a preservation of both trabecular and cortical bone, as well as a dramatic reduction in the accumulation of marrow fat. Consistent with such findings, mechanical testing revealed that the bones of intermittently methionine-restricted mice are significantly stronger than those of mice subjected to the continuous intervention. Finally, static histomorphometric analyses suggest that IMR likely results in more bone mass than that produced by continuous MR, primarily by increasing the number of osteoblasts. Together, our results demonstrate that the more practicable intermittent form of MR not only confers similar metabolic health benefits to the continuous intervention but does so without markedly deleterious effects on either the amount or strength of bone. These data provide further support for the use of IMR in humans.

Dataset Information

Dietary Methionine Restriction Reduces Inflammation Independent of FGF21 Action.

Objective

Methods

Results

Conclusions

Publications

Dietary Methionine Restriction Reduces Inflammation Independent of FGF21 Action.

Similar Datasets

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