Protection against the Metabolic Syndrome by Guar Gum-Derived Short-Chain Fatty Acids Depends on Peroxisome Proliferator-Activated Receptor γ and Glucagon-Like Peptide-1

Gijs Den Besten,Albert K Groen,Rick Havinga,Barbara M Bakker,Aycha Bleeker,Theo H Van Dijk,Albert Gerding,Dirk-Jan Reijngoud,Jolita Ciapaite,Karen Van Eunen

doi:10.1371/journal.pone.0136364

Gijs Den Besten, Albert K Groen + Show 8 more

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https://doi.org/10.1371/journal.pone.0136364

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Abstract

The dietary fiber guar gum has beneficial effects on obesity, hyperglycemia and hypercholesterolemia in both humans and rodents. The major products of colonic fermentation of dietary fiber, the short-chain fatty acids (SCFAs), have been suggested to play an important role. Recently, we showed that SCFAs protect against the metabolic syndrome via a signaling cascade that involves peroxisome proliferator-activated receptor (PPAR) γ repression and AMP-activated protein kinase (AMPK) activation. In this study we investigated the molecular mechanism via which the dietary fiber guar gum protects against the metabolic syndrome. C57Bl/6J mice were fed a high-fat diet supplemented with 0% or 10% of the fiber guar gum for 12 weeks and effects on lipid and glucose metabolism were studied. We demonstrate that, like SCFAs, also guar gum protects against high-fat diet-induced metabolic abnormalities by PPARγ repression, subsequently increasing mitochondrial uncoupling protein 2 expression and AMP/ATP ratio, leading to the activation of AMPK and culminating in enhanced oxidative metabolism in both liver and adipose tissue. Moreover, guar gum markedly increased peripheral glucose clearance, possibly mediated by the SCFA-induced colonic hormone glucagon-like peptide-1. Overall, this study provides novel molecular insights into the beneficial effects of guar gum on the metabolic syndrome and strengthens the potential role of guar gum as a dietary-fiber intervention.

Highlights

The growing prevalence of diseases clustered in the metabolic syndrome is accompanied by a shift in diet in Western and developing countries from a traditional low-calorie diet with highfiber and low-fat content towards a high-calorie diet with low-fiber and high-fat content [1,2]
high-fat diet (HFD) induced body weight (BW) gain, while guar gum supplementation attenuated the increase in BW (Fig 1A) and concomitantly reduced the mass of white adipose tissue (WAT) (Fig 1B)
We demonstrated that guar gum protects against HFD-induced obesity and insulin resistance through the same signaling cascade in liver and adipose tissue as supplemented short-chain fatty acids (SCFAs)

Summary

Introduction

The growing prevalence of diseases clustered in the metabolic syndrome is accompanied by a shift in diet in Western and developing countries from a traditional low-calorie diet with highfiber and low-fat content towards a high-calorie diet with low-fiber and high-fat content [1,2]. Epidemiological studies revealed an inverse correlation between dietary fiber intake and the metabolic syndrome [3], suggesting that fiber supplementation to the diet may be beneficial. A variety of studies have shown that dietary fiber intervention decreased obesity and insulin resistance in both healthy and metabolic syndrome patients (reviewed by Galisteo et al [1]). The beneficial effects of dietary fibers work through the intestinal microbiota [8]. SCFAs have been suggested to play a major role in the dietary fiber-induced beneficial effects. We showed that dose-dependent effects of guar gum-supplementation on body weight and insulin sensitivity correlate with the rate of SCFA uptake by the host, but not with their cecal concentration [10], suggesting that fiber-derived SCFAs need to be taken up to exert their full physiological effect

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