Hydroxytyrosol Inhibits Cannabinoid CB1 Receptor Gene Expression in 3T3‐L1 Preadipocyte Cell Line

Abstract

The 3T3-L1 preadipocyte cell line is a well characterized cell model for studying the adipocyte status and the molecular mechanisms involved in differentiation of these cells. 3T3-L1 preadipocytes have the ability to synthesize and degrade endocannabinoid anandamide (AEA) and their differentiation into adipocytes increases the expression of cannabinoid (CB1) and PPAR-γ receptors. Clinically, the blocking stimulation of the endocannabinoid pathway has been one of the first approaches proposed to counteract the obesity and obesity-associated diseases (such as diabetes, metabolic syndrome and cancer). In this connection, here we studied in cultured 3T3-L1 pre-adipocytes the effects of n-3-PUFA, α-Linolenic acid (OM-3), n-6-PUFA, Linoleic acid (OM-6), and hydroxytyrosol (HT) on the expression of CB1 receptor gene and the adipogenesis-related genes PPAR-γ, Fatty Acid Synthase (FAS) and Lipoprotein Lipase (LPL). HT was able to inhibit 3T3-L1 cell differentiation by down-regulating cell proliferation and CB1 receptor gene expression. HT exhibited anti-adipogenic effects, whereas OM-3 and OM-6 exerted an inhibitory action on cell proliferation associated with an induction of the preadipocytes differentiation and CB1 receptor gene expression. Moreover, the expression of FAS and LPL genes resulted increased after treatment with both HT and OM-3 and OM-6. The present study points out that the intake of molecules such as HT, contained in extra virgin olive oil, may be considered also in view of antiobesity and antineoplastic properties by acting directly on the adipose tissue and modulating CB1 receptor gene transcription.

Caffeic acid and hydroxytyrosol have anti-obesogenic properties in zebrafish and rainbow trout models

“…The decrease in WAT fasn mRNA levels produced by HT treatment was accompanied by a reduction in plasma TAG levels, possibly due to the antagonist effect of this compound on the PPARγ signaling pathway. In agreement with our results, some mammal studies have demonstrated that CA and HT regulate WAT mass by suppressing lipogenic enzyme activity and claimed that PPARγ antagonists can be used to treat hyperlipidemia [74,75]. Interestingly, HT also downregulated pnpla2 transcript abundance in rainbow trout WAT, which is indicative of decreased lipolysis, leading to a reduction in lipid turnover or compensation for excessive WAT decrease.…”

Changes in Plasma Fatty Acids, Free Amino Acids, Antioxidant Defense, and Physiological Stress by Oleuropein Supplementation in Pigs Prior to Slaughter

“…It has been suggested that oleuropein may alter catecholamine synthesis in the brain [47]. On the other hand, it has been reported that hydroxytyrosol, another antioxidant substance extracted from olive leaves, may affect the endocannabinoid system by inhibition of its receptors (CB1) [12]. The endocananabonoid system is not only involved in energy regulation in the organism as a metabolic signaling system, but also in the stress response [17].…”

“…It has been suggested that it activates glucose consumption in a dose-dependent manner in adipocytes and in myotubes [10], and may reduce lipid levels by suppressing lipid synthesis and promoting fatty acid oxidation via the regulation of adenosine monophosphate-activated protein kinase (AMPK) [11]. Recently, it has been reported that olive extracts may modulate cannabinoid receptor (CB1) gene expression, which regulates energy homeostasis in the organism [12]. Due to its effects shown on glucose uptake and lipid metabolism, its use by dietary interventions might affect a specific fatty acid mobilization and glycogen stores as well as amino acid utilization [13]; however, there is no information on the specific mobilization of the fatty acid or free amino acid profile prior to slaughter in fasting conditions.…”

Cell Models and Their Application for Studying Adipogenic Differentiation in Relation to Obesity: A Review

“…Because of this, 3T3-L1 cells have been extensively over the last five years to evaluate the effects of compounds or nutrients on adipogenesis, to establish the underlying molecular mechanisms of adipogenesis and to evaluate the potential application of various compounds and nutrients in the treatment of obesity [ 30 , 31 , 32 ]. Particularly, compounds such as quercetin [ 33 , 34 ] and resveratrol [ 35 , 36 ] inhibit adipogenesis in 3T3-L1 adipocytes.…”