Transgenerational supplementation with eicosapentaenoic acid reduced the metabolic consequences on the whole body and skeletal muscle in mice receiving an obesogenic diet

Abstract

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

“…Protection of offspring from weight gain, oxidative stress, and alteration in FA oxidation was demonstrated in animals with Fat1 overexpression that could increase the bioconversion of n-6 to n-3 PUFA [29]. We previously reported that transgenerational intake of EPA (provided by fish oil rich in EPA) could reduce body fat gain and cardiometabolic risk in offspring from the third generation when fed an obesogenic diet [23]. The current study aimed to investigate the specific transcriptomic adaptations in VAT during the development of obesity in these mice, which were compared to a control lineage that received an isocaloric supplementation with a high-oleic sunflower oil.…”

“…The current study aimed to investigate the specific transcriptomic adaptations in VAT during the development of obesity in these mice, which were compared to a control lineage that received an isocaloric supplementation with a high-oleic sunflower oil. We have previously reported the limitation of fibrotic, inflammatory, and anti-metabolic processes in the muscle and liver from these animals [23,24]. However, the biological and molecular adaptations induced by transgenerational intake of n-3 PUFA in the AT remained to be explored.…”

“…Transgenerational supplementation with n-6 or n-3 PUFA could induce specific biological adaptations, which could affect fatty acid metabolism and susceptibility to fat mass accretion [12]. We observed that transgenerational supplementation with fish oil (1% of the diet), rich in EPA, reduced the activation of fibrotic processes in skeletal muscle and contributed to a better metabolic flexibility in the liver in F3 mice exposed to an obesogenic diet through several molecular adaptations [23,24], but the consequences on the AT remained to be explored. As the AT dysfunctions are a key element in the progression of obesity-related comorbidities, nutritional strategies using n-3 PUFA, and aiming at the improvement of its secretory and metabolic activities, were proposed [25].The aim of the present study was to explore how the transgenerational supplementation with n-3 PUFA, mainly in the form of EPA, affected adipose tissue biology and adaptation after an obesogenic challenge.…”

“…The details of the breeding strategy to obtain three generations of mice receiving a supplementation with EPA and of the obesogenic challenge could be found in Section 4.1. We previously described that the biometric and metabolic consequences of 17 weeks of an obesogenic diet differed between F3 mice from the EPA lineage (HFepa) compared to a control/oleic lineage (HFoleic) [23]. Briefly, 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 ( group "Ref") receiving a normocaloric diet.…”

“…Evidence was also provided about the improvement of adipose tissue secretory profile and inflammation in rodents receiving a high-fat diet supplemented with n-3 PUFA [21,22]. Recently, our group has demonstrated that dietary supplementation of three generations of mice with EPA could alleviate the deleterious metabolic impact of an obesogenic diet [23] in the third generation (F3 mice). Transgenerational supplementation with n-6 or n-3 PUFA could induce specific biological adaptations, which could affect fatty acid metabolism and susceptibility to fat mass accretion [12].…”