Original Research: Hydroxytyrosol, an ingredient of olive oil, reduces triglyceride accumulation and promotes lipolysis in human primary visceral adipocytes during differentiation

Abstract

Hydroxytyrosol has various pharmacological properties, including anti-oxidative stress and anti-inflammatory activities, preventing hyperglycemia, insulin resistance, and the metabolic syndrome. The present study is focused on the anti-adipogenic and lipolytic activity of hydroxytyrosol on primary human visceral adipocytes. Pre-adipocytes were analyzed after 10 (P10) and 20 (P20) days of treatment during differentiation and after 7 (A7) days of treatment when they reached mature shape. The treatment with hydroxytyrosol extract significantly (P < 0.001) increased apoptosis in P10 and P20 cells in comparison to control and A7 cells; significantly (P < 0.001) reduced triglyceride accumulation in P20 cells compared to P10 and control cells; and significantly (P < 0.001) increased lipolysis in P20 cells in comparison to control cells and A7 mature adipocytes. Hydroxytyrosol-treated P20 cells significantly (P < 0.05) increased expression of genes involved in inhibition of adipogenesis, such as GATA2, GATA3, WNT3A, SFRP5, HES1, and SIRT1. In contrast, genes involved in promoting adipogenesis such as LEP, FGF1, CCND1, and SREBF1 were significantly down-regulated by hydroxytyrosol treatment. These data suggest that hydroxytyrosol promotes lipolysis and apoptotic activity in primary human visceral pre-adipocytes during differentiation and does not affect already mature adipocytes.

Factors involved in white‐to‐brown adipose tissue conversion and in thermogenesis: a review

“…It is present also as an aglycone and gives a pungent taste to olive oil. It has been recognized as a powerful antioxidant compound and also has anti‐obesity properties, like many other molecules detected in olive oil, including hydroxytyrosol . Studies on rats confirmed that anti‐obesity effect of oleuropein and oleuropein aglycone is achieved through the activation of thermogenesis in BAT and an increased release of both epinephrine and NE, which in turn activates lipolytic pathways in AT.…”

Hydroxytyrosol, Tyrosol and Derivatives and Their Potential Effects on Human Health

“…It was shown that HTyr has beneficial effect in hyperlipidemia as it modifies genes related with adipocyte maturation and differentiation and inhibits lipid formation [78]. HTyr was shown to be effective towards the mobilization of lipids [79]. Also, HTyr has beneficial effect on obesity by suppressing dose-dependently intracellular TG accumulation and the expression of adipogenesis-stimulating factors during adipocyte differentiation, promotes lipolysis in human primary visceral adipocytes during differentiation and decreases hepatic steatosis [80,81].…”

Antidiabetic Effects of Hydroxytyrosol: In Vitro and In Vivo Evidence

“…A new proposed approach includes molecules that may potentially modulate endocannabinoid receptor gene expression [39]. Another study showed that exposure of human primary visceral preadipocytes to HT (5–70 µg/mL) resulted in decreased triglyceride accumulation and increased apoptosis, lipolysis, glycerol release and expression of adipogenesis inhibiting genes such as GATA- binding factor 2 and 3 (GATA2 and GATA3) [40], protein Wnt-3A (WNT3A), secreted frizzled-related protein 5 (SFRP5), hairy and enhancer of split-1 (HES1), and NAD-dependent deacetylase sirtuin-1 (SIRT1). Additionally, genes involved in promoting adipogenesis including leptin (LEP), sterol regulatory element-binding protein 1 (SREBF1), Cyclin D1 (CCND1) and fibroblast growth factor 1 (FGF1) were significantly downregulated [40].…”

“…Another study showed that exposure of human primary visceral preadipocytes to HT (5–70 µg/mL) resulted in decreased triglyceride accumulation and increased apoptosis, lipolysis, glycerol release and expression of adipogenesis inhibiting genes such as GATA- binding factor 2 and 3 (GATA2 and GATA3) [40], protein Wnt-3A (WNT3A), secreted frizzled-related protein 5 (SFRP5), hairy and enhancer of split-1 (HES1), and NAD-dependent deacetylase sirtuin-1 (SIRT1). Additionally, genes involved in promoting adipogenesis including leptin (LEP), sterol regulatory element-binding protein 1 (SREBF1), Cyclin D1 (CCND1) and fibroblast growth factor 1 (FGF1) were significantly downregulated [40]. On the other hand, Anter et al 2016 showed that exposure of human bone marrow mesenchymal stem cells (MSCs) to HT (100 µM) as they differentiated into adipocytes, resulted inupregulated adipocyte differentiation genes such as PPARγ and fatty-acid binding protein 4 (FABP4) as well as fat vesicle formation in the MSC adipocytes.…”