Adipose Tissue Dysfunctions in Response to an Obesogenic Diet Are Reduced in Mice after Transgenerational Supplementation with Omega 3 Fatty Acids

Alexandre Pinel,Frédéric Capel,Béatrice Morio,Jean-Paul Rigaudière

doi:10.3390/metabo11120838

Abstract

Obesity is characterized by profound alterations in adipose tissue (AT) biology, leading to whole body metabolic disturbances such as insulin resistance and cardiovascular diseases. These alterations are related to the development of a local inflammation, fibrosis, hypertrophy of adipocytes, and dysregulation in energy homeostasis, notably in visceral adipose tissue (VAT). Omega 3 (n-3) fatty acids (FA) have been described to possess beneficial effects against obesity-related disorders, including in the AT; however, the long-term effect across generations remains unknown. The current study was conducted to identify if supplementation with n-3 polyunsaturated FA (PUFA) for three generations could protect from the consequences of an obesogenic diet in VAT. Young mice from the third generation of a lineage receiving a daily supplementation (1% of the diet) with fish oil rich in eicosapentaenoic acid (EPA) or an isocaloric amount of sunflower oil, were fed a high-fat, high-sugar content diet for 4 months. We explore the transcriptomic adaptations in each lineage using DNA microarray in VAT and bioinformatic exploration of biological regulations using online databases. Transgenerational intake of EPA led to a reduced activation of inflammatory processes, perturbation in metabolic homeostasis, cholesterol metabolism, and mitochondrial functions in response to the obesogenic diet as compared to control mice from a control lineage. This suggests that the continuous intake of long chain n-3 PUFA could be preventive in situations of oversupply of energy-dense, nutrient-poor foods.

Highlights

IntroductionAlteration of White adipose tissue (WAT) physiology during obesity leads to insulin resistance, low grade inflammation, perturbation of fuel selection by metabolic tissues, contributing to a global alteration of energy homeostasis
We previously described that the biometric and metabolic consequences of 17 weeks of an obesogenic diet differed between F3 mice from the eicosapentaenoic acid (EPA) lineage (HFepa) compared to a control/oleic lineage (HFoleic) [23]
HFepa mice gained less weight, fat mass, and exhibited better metabolic function compared to HFoleic mice and to a reference group of F3 mice from the control lineage/oleic receiving a normocaloric diet

Summary

Introduction

Alteration of WAT physiology during obesity leads to insulin resistance, low grade inflammation, perturbation of fuel selection by metabolic tissues, contributing to a global alteration of energy homeostasis. These abnormalities are crucial factors of the increased risk for disability and mortality and the strong socioeconomic impact of obesity [5]. Most healthy and preventive lifestyle recommendations aim at increase physical activity, and reduce energy intake by eating a diet rich in fruits and vegetables and poor in sugars. Such a diet should provide natural bioactive compounds with antioxidant and anti-inflammatory properties [6]. N-3 PUFAs are bioactive nutrients with protective roles against endothelial dysfunctions, inflammation, heart disease, and obesity [10,11]

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