Abstract
In recent years, obesity has become a key factor affecting human health. Moringa oleifera Lam. is a perennial tropical deciduous tree, which is widely used in human medicine due to its nutritional and unique medicinal value. It has a cholesterol-lowering effect, but its mechanism of action is unclear. In this study, we elucidated the inhibitory effect of M. oleifera leaf petroleum ether extract (MOPEE) on lipid accumulation by in vitro and in vivo experiments, and we described its mechanism of action. MOPEE suppressed adipogenesis in 3T3-L1 adipocytes in a dose-dependent manner and had no effect on cell viability at doses up to 400 μg/ml. Furthermore, MOPEE (400 μg/ml) significantly downregulated the expression of adipogenesis-associated proteins [peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding proteins α and β (C/EBPα and C/EBPβ), and fatty acid synthase (FAS)] and upregulated the expression of a lipolysis-associated protein [hormone-sensitive lipase (HSL)] in 3T3-L1 adipocytes. Additionally, MOPEE (400 μg/ml) significantly increased the degree of phosphorylation of AMP-activated protein kinase α (AMPKα) and acetyl-CoA carboxylase (ACC). An AMPK inhibitor reversed the MOPEE-induced activation of AMPKα and ACC in 3T3-L1 adipocytes. Animal experiments showed that, in high-fat diet (HFD) mice, MOPEE [0.5 g/kg body weight (BW)] effectively decreased BW; relative epididymal, perirenal, and mesenteric fat weight and fat tissue size; and hepatic fat accumulation. Furthermore, MOPEE markedly reduced the serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and aspartate aminotransferase (AST). Moreover, MOPEE significantly downregulated the expression of adipogenesis-associated proteins (PPARγ and FAS) and upregulated the expression of a lipolysis-associated protein [adipose triglyceride lipase (ATGL)] in HFD mice hepatic and epididymal fat tissue. Additionally, MOPEE markedly increased the degree of phosphorylation of AMPKα and ACC in HFD mice hepatic and epididymal fat tissue. Following ultrahigh-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS) analysis, three phytocompounds (isoquercitrin, chrysin-7-glucoside, and quercitrin) were identified as compounds with relatively high levels in MOPEE. Among them, quercitrin showed excellent fat accumulation inhibitory activity, and the three compounds had synergistic effects in inhibiting adipogenesis. Taken together, MOPEE inhibits fat accumulation by inhibiting the adipogenesis and promoting the lipolysis, and this process is related to AMPK activation.
Highlights
Metabolic syndrome is a clustering of risk factors, such as central obesity, insulin resistance, dyslipidemia, and hypertension, which together culminate in increased risk of type 2 diabetes mellitus and cardiovascular disease (O’Neill and O’Driscoll, 2015)
We found that the four extracts had no effect on the survival rate of 3T3-L1 adipocytes compared to the untreated control group (Figure 1A)
To detect which extracts could inhibit adipogenesis, 3T3-L1 adipocytes were exposed to the four extracts of M. oleifera leaf (25–400 μg/ml) for 24 h, and the intracellular TG was quantified
Summary
Metabolic syndrome is a clustering of risk factors, such as central obesity, insulin resistance, dyslipidemia, and hypertension, which together culminate in increased risk of type 2 diabetes mellitus and cardiovascular disease (O’Neill and O’Driscoll, 2015). Truncal obesity plays an exceptionally critical role among all the metabolic traits of the metabolic syndrome, and the prevalence of metabolic syndrome has steadily increased with the growing epidemic of obesity (Martin et al, 2015). The occurrence of obesity is closely associated with genetic and environmental factors; environmental factors mainly include eating habits and lifestyle (Lai et al, 2015). Obesity is characterized by pathologic growth of adipose tissues to accommodate excess energy intake by increasing the volume and number of adipocytes in the body. The proliferation and differentiation of preadipocytes play an extremely important role in this process. Inhibiting the preadipocyte proliferation and differentiation (adipogenesis) is one of the methods to prevent and treat obesity (Figarola and Rahbar, 2013)
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