Elsevier

Biochimie

Volume 159, April 2019, Pages 66-71
Biochimie

Mini-review
N-3 polyunsaturated fatty acids: An innovative strategy against obesity and related metabolic disorders, intestinal alteration and gut microbiota dysbiosis

https://doi.org/10.1016/j.biochi.2019.01.017Get rights and content

Highlights

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    N-3 fatty acids exert preventive effects on diet-induced obesity and related metabolic disorders.

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    Endogenous n-3 PUFAs enrichment in fat-1 mice maintains the intestinal barrier integrity and lowers metabolic endotoxemia.

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    Transfer of fecal microbiota of fat-1 to wild type mice replicates n-3 PUFAs benefic effects observed.

Abstract

Obesity is now widely recognized to be associated with low-grade systemic inflammation. It has been shown that high-fat feeding modulates gut microbiota which strongly increased intestinal permeability leading to lipopolysaccharide absorption causing metabolic endotoxemia that triggers inflammation and metabolic disorders. N-3 polyunsaturated fatty acids (PUFAs) have been shown associated with anti-obesity properties, but results still remain heterogeneous and very few studies underlined the metabolic pathways involved. Thus, the use of Fat-1 transgenic mice allows to better understanding whether endogenous n-3 PUFAs enrichment contributes to obesity and associated metabolic disorders prevention. It specially evidence that such effects occur through modulations of gut microbiota and intestinal permeability. Then, by remodeling gut microbiota, endogenous n-3 PUFAs improve HF/HS-diet induced features of the metabolic syndrome which in turn affects host metabolism. Thus, increasing anti-obesogenic microbial species in the gut microbiota population (i.e Akkermansia) by appropriate n-3 PUFAs may represent a promising strategy to control or prevent metabolic diseases.

Introduction

Obesity, defined as an abnormal or excessive fat accumulation, is now recognized as an international public health concern. Indeed, in the world, more than 2.1 billion people have a body mass index (BMI) ≥ 25.0 and ≥30.0 in more than half a billion of them with no distinction of age or sex. Although obesity is considered as a multifactorial pathology (genetic predisposition, environmental impact, lack of physical activity …), the leading cause of obesity development is the rising consumption of high-fat/high-sucrose (HF/HS) diets -especially in western countries - and efforts still need to be done to identify factors that would prevent or cure this pathology. Obesity is also associated with increased risk of developing a wide cluster of alterations such as insulin resistance (IR), dyslipidemia, hypertension, diabetes known to be the main components of the metabolic syndrome [1] and of non-alcoholic fatty liver diseases [2].

Section snippets

Obesity and low grade inflammation: role of LPS

Nowadays, obesity is linked to low-grade systemic inflammation which is identified as a key factor of its development and of related metabolic disorders [[3], [4], [5]], even if the molecular origin of such inflammation is not fully elucidated. Cani and co-workers [6] have identified major bacterial components, lipopolysaccharides (LPS), mainly found in the outer membrane of Gram-negative bacteria, as a triggering factor of metabolic endotoxemia when it translocates in the bloodstream, which

N-3 polyunsaturated fatty acids, obesity and related disorders

In this last decade, many studies both in animal and human have focused on the cardioprotective effects of fish oils. Increasing the feeding of n-3 polyunsaturated fatty acids (PUFAs) represents a promising approach [12] against obesity-associated diseases. Thus, the physiological functions and molecular actions of these unsaturated fatty acids have been investigated in the context of obesity, and thanks to their functional properties they could be considered useful to fight metabolic syndrome

N-3 PUFAs, intestinal permeability and microbiota in the context of obesity

Dietary n-3 PUFAs, affecting gut integrity, have been shown to reduce clinical colitis and colonic immunopathology by improving epithelial barrier function in animal models [37,38]. EPA has been shown to up-regulate the expression of tight junctions and to increase the trans-epithelial electrical resistance (TER), thus reducing the permeability of the endothelial cells [39]. EPA and DHA, by lowering permeability-induced inflammatory cytokines such as TNFα, IFNγ and IL-4, can maintain gut

The fat-1 mice: an appropriate model for studying obesity

In obesity-related studies, fat-1 mice represent an innovative animal model that overcomes the use of dietary manipulation helpful for avoiding any confounding dietary elements brought by diets. Indeed, these transgenic mice ubiquitously express a gene coming from C. Elegans, which encodes for a n-3 fatty acid desaturase able to convert n-6 to n-3 PUFAs [55] leading to a remarkable tissue enrichment in n-3 PUFAs compared with WT. Moreover, in this mouse model, tissue contents in n-3 PUFAs not

Remodeling gut microbiota by endogenously synthesized n-3 fatty acids prevents high fat/high sucrose diet-induced metabolic endotoxemia and associated metabolic disorders

In the context of obesity, remodeling the gut microbiome could be a promising therapeutic target. Then, it has recently been pointed out in mice the relative contribution of endogenously synthesized n-3 PUFAs in altering gut microbiota in order to change metabolic parameters [28,57].

Conclusions and future prospects

Altogether, these data evidence that n-3 PUFAs represent a promising approach in the prevention and treatment of obesity and associated disorders. Indeed, by the use of transgenic fat-1 mice avoiding nutritional confounding factors, tissue n-3 PUFAs enrichment indisputably demonstrates that these functional fatty acids prevent weight gain, glucose intolerance, liver steatosis inflammation and leaky gut. Moreover such tissue enrichment unexpectedly change gut microbiota composition (a peculiar

Acknowledgement

This work was supported by INSERM, the Regional Council of Bourgogne, the European Regional Development Fund, the University of Bourgogne, the Fondation de France, a CIFRE grant from Valorex (Combourtillié, France), and a French government grant managed by the French National Research Agency (ANR) under the program “Investissements d’Avenir” with reference ANR-11-LABX-0021-01-LipSTIC LabEx.

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