Abstract
Aquilaria sinensis (Lour.) Spreng is known for its resinous secretion (agarwood), often secreted in defense against injuries. We investigated the effects of A. sinensis flower extract (AF) on peroxisome proliferator-activated receptors alpha and gamma (PPARα and PPARγ), liver X receptor (LXR), glucose uptake, and lipid accumulation (adipogenesis). Activation of PPARα, PPARγ and LXR was determined in hepatic (HepG2) cells by reporter gene assays. Glucose uptake was determined in differentiated muscle (C2C12) cells using 2-NBDG (2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose). Adipogenesis was determined in adipocytes (3T3-L1 cells) by Oil red O staining. At a concentration of 50 µg/mL, AF caused 12.2-fold activation of PPARα and 5.7-fold activation of PPARγ, while the activation of LXR was only 1.7-fold. AF inhibited (28%) the adipogenic effect induced by rosiglitazone in adipocytes and increased glucose uptake (32.8%) in muscle cells at 50 μg/mL. It was concluded that AF acted as a PPARα/γ dual agonist without the undesired effect of adipogenesis and exhibited the property of enhancing glucose uptake. This is the first report to reveal the PPARα/γ dual agonistic action and glucose uptake enhancing property of AF along with its antiadipogenic effect, indicating its potential in ameliorating the symptoms of metabolic syndrome.
Highlights
Metabolic syndrome is defined by the World Health Organization (WHO) as a pathological condition characterized by hyperlipidemia, hypertension, abdominal obesity, and insulin resistance [1]
PPARs are highly expressed in macrophages, adipose tissue and hepatocytes, and play important roles in adipogenesis, lipid metabolism, glucose homeostasis, and immune regulation [32]
Thiazolidinedione class of antidiabetic drugs acting through a full PPARγ agonistic effect, is hampered by adverse effects related to increased weight gain and fluid retention due to enhanced adipogenesis
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Metabolic syndrome is defined by the World Health Organization (WHO) as a pathological condition characterized by hyperlipidemia, hypertension, abdominal obesity, and insulin resistance [1]. The incidence of metabolic syndrome often parallels the incidence of obesity and of type 2 diabetes [2]. Considering the association of metabolic syndrome with obesity, it is quite likely that in a high percentage of these predominantly obese patients, the dysfunction of their adipose tissue becomes a main contributor to the subsequent associated complications. Phytochemicals belonging to polyphenols and flavonoids have been found to improve metabolic syndrome through their beneficial effects against lipid accumulation, high blood pressure and increased blood glucose [3,4]
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