Protective Effects of Eicosapentaenoic Acid Plus Hydroxytyrosol Supplementation Against White Adipose Tissue Abnormalities in Mice Fed a High-Fat Diet.

Paola Illesca,Francisca Echeverría,Luis A Videla,Rodrigo Valenzuela,Alejandra Espinosa,Cristian Campos,Thea Magrone,Romina Vargas,Sandra Soto-Alarcon,Alicia Rodriguez

doi:10.3390/molecules25194433

Abstract

Objective: Obesity induced by high-fat diet (HFD) elicits white adipose tissue dysfunction. In this study, we have hypothesized that the metabolic modulator eicosapentaenoic acid (EPA) combined with the antioxidant hydroxytyrosol (HT) attenuates HFD-induced white adipose tissue (WAT) alterations. Methods: C57BL/6J mice were administered with a HFD (60% fat, 20% protein, 20% carbohydrates) or control diet (CD; 10% fat, 20% protein, 70% carbohydrates), with or without EPA (50 mg/kg/day), HT (5 mg/kg/day), or both for 12 weeks. Determinations in WAT include morphological parameters, EPA and docosahexaenoic acid content in phospholipids (gas chromatography), lipogenesis, oxidative stress (OS) and inflammation markers, and gene expression and activities of transcription factors, such as sterol regulatory element-binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor-gamma (PPAR-γ), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) (p65 subunit) and nuclear factor erythroid 2-related factor 2 (Nrf2) (quantitative polymerase chain reaction and enzyme linked immunosorbent assay). Results: HFD led to WAT hypertrophy in relation to PPAR-γ downregulation. WAT metabolic dysfunction was characterized by upregulation of lipogenic SREBP-1c system, mitochondrial energy metabolism depression, loss of the antioxidant Nrf2 signaling with OS enhancement, n-3 long-chain polyunsaturated fatty acids depletion and activation of the pro-inflammatory NF-κB system. EPA and HT co-supplementation diminished HFD-dependent effects additively, reaching values close or similar to controls. Conclusion: Data presented strengthen the importance of combined protocols such as EPA plus HT to attenuate metabolic-inflammatory states triggered by obesity.

Highlights

Overweight and obesity have been defined by the World Health Organization (WHO) as the abnormal or excessive fat accumulation that may impair health [1]
high-fat diet (HFD) led to an increase in body weight (BW) gain of 65% (p < 0.05), compared with control diet (CD) groups, which is related with to augmented adiposity (Table 2A, group e)
Dietary intake was comparable in all experimental groups, but energy consumption was higher in mice subjected to the HFD with or without supplementation over CD groups (Data not shown)

Summary

Introduction

Overweight and obesity have been defined by the World Health Organization (WHO) as the abnormal or excessive fat accumulation that may impair health [1]. The fat accumulation that characterizes obesity promotes white adipose tissue (WAT) expansion, altering its normal functions These include hypertrophy contributing to development of oxidative stress, the activation of low-grade inflammatory response and dysregulation of lipolysis accompanied by insulin resistance (IR) [6]. EPA is biosynthesized from the essential precursor α-linolenic acid ((C18:3n-3), ALA) through desaturation and elongation reactions occurring primarily in the liver, with actions being exerted on signal transduction pathways and gene transcription [8] These include downregulation of lipogenic sterol regulatory element-binding protein-1c (SREBP-1c), upregulation of peroxisome proliferator-activated receptor-α (PPAR-α) favoring fatty acid oxidation (FAO) and promotion of inflammation resolution via synthesis of specific pro-resolving mediators (SPMs) [9].

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Conclusion