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. 2020 May:79:108352.
doi: 10.1016/j.jnutbio.2020.108352. Epub 2020 Feb 4.

Quercetin attenuates adipose hypertrophy, in part through activation of adipogenesis in rats fed a high-fat diet

Diahann J Perdicaro  1 , Cecilia Rodriguez Lanzi  1 , Julián Gambarte Tudela  2 , Roberto M Miatello  1 , Patricia I Oteiza  3 , Marcela A Vazquez Prieto  4
Affiliations

Quercetin attenuates adipose hypertrophy, in part through activation of adipogenesis in rats fed a high-fat diet

Diahann J Perdicaro et al. J Nutr Biochem. 2020 May.

Abstract

An impaired capacity of adipose tissue expansion leads to adipocyte hypertrophy, inflammation and insulin resistance (IR) under positive energy balance. We previously showed that a grape pomace extract, rich in flavonoids including quercetin (Q), attenuates adipose hypertrophy. This study investigated whether dietary Q supplementation promotes adipogenesis in the epididymal white adipose tissue (eWAT) of rats consuming a high-fat diet, characterizing key adipogenic regulators in 3T3-L1 pre-adipocytes. Consumption of a high-fat diet for 6 weeks caused IR, increased plasma TNFα concentrations, eWAT weight, adipocyte size and the eWAT/brown adipose tissue (BAT) ratio. These changes were accompanied by decreased levels of proteins involved in angiogenesis, VEGF-A and its receptor 2 (VEGF-R2), and of two central adipogenic regulators, i.e. PPARγ and C/EBPα, and proteins involved in mature adipocyte formation, i.e. fatty acid synthase (FAS) and adiponectin. Q significantly reduced adipocyte size and enhanced angiogenesis and adipogenesis without changes in eWAT weight and attenuated systemic IR and inflammation. In addition, high-fat diet consumption increased eWAT hypoxia inducible factor-1 alpha (HIF-1α) levels and those of proteins involved in adipose inflammation (TLR-4, CD68, MCP-1, JNK) and activation of endoplasmic reticulum (ER) stress, i.e. ATF-6 and XBP-1. Q mitigated all these events. Q and quercetin 3-glucoronide prevented TNFα-mediated downregulation of adipogenesis during 3T3-L1 pre-adipocytes early differentiation. Together, Q capacity to promote a healthy adipose expansion enhancing angiogenesis and adipogenesis may contribute to reduced adipose hypertrophy, inflammation and IR. Consumption of diets rich in Q could be useful to counteract the adverse effects of high-fat diet-induced adipose dysfunction.

Keywords: Adipogenesis; Adipose tissue; Angiogenesis; Inflammation; Quercetin.

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