Hydroxytyrosol supplementation ameliorates the metabolic disturbances in white adipose tissue from mice fed a high-fat diet through recovery of transcription factors Nrf2, SREBP-1c, PPAR-γ and NF-κB

Abstract

BACKGROUND: White adipose tissue (WAT) have a relevant metabolic and inflammatory function, in overweight or obesity conditions. In this regard, the WAT under over feeding nutrition present a significant increment in oxidative stress, pro-inflammatory status and depletion of n-3 long chain polyunsaturated fatty acid. Hydroxytyrosol (HT) is a polyphenol with important cytoprotective effects, and this molecule can modulate the gene expression, transcription factors and enzymatic activity. OBJECTIVE: Therefore, the purpose of this study was evaluate the anti-inflammatory, anti-oxidant and anti-lipogenic effects of HT supplementation mice and the molecular adaptations involved, on dysfunctional WAT from high-fat diet (HFD)-fed mice. METHODS AND RESULTS: Male C57BL/6 J mice received (i) control diet (10% fat); (ii) control diet + HT (daily doses of 5 mg kg body weight), (iii) HFD (60% fat); or (iv) HFD + HT for 12 weeks. HFD-fed mice exhibited: (i) WAT hypertrophy; (ii) oxidative stress and depletion of antioxidant defenses, (iii) increased lipogenesis and pro-inflammatory status, (iv) depletion of n-3 LCPUFA and (v) up-regulation of NF-κB and SREBP 1c with down-regulation Nrf2, and PPAR-γ. HT supplementation attenuated the metabolic impairment produced by HFD in WAT, attenuating increment of NF-κB and SREBP 1c, and increasing the activity of Nrf2 and PPAR-γ. CONCLUSION: Supplementation with HT improve the WAT dysfunction induced by HDF in mice through the modulation of transcription factors NF-κB, Nrf2, SREBP-1c and PPAR-γ as well as their target genes, involved in inflammation, antioxidant defenses and lipogenesis.