Abstract
The Chrysanthemum morifolium Ramat (CM) is widely used as a traditional medicine and herbal tea by the Asian population for its health benefits related to obesity. However, compared to the flowers of CM, detailed mechanisms underlying the beneficial effects of its leaves on obesity and dyslipidemia have not yet been elucidated. Therefore, to investigate the lipidomic biomarkers responsible for the pharmacological effects of CM leaf extract (CLE) in plasma of mice fed a high-fat diet (HFD), the plasma of mice fed a normal diet (ND), HFD, HFD plus CLE 1.5% diet, and HFD plus luteolin 0.003% diet (LU) for 16 weeks were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) combined with multivariate analysis. In our analysis, the ND, HFD, CLE, and LU groups were clearly differentiated by partial least-squares discriminant analysis (PLS-DA) score plots. The major metabolites contributing to this differentiation were cholesteryl esters (CEs), lysophosphatidylcholines (LPCs), phosphatidylcholines (PCs), ceramides (CERs), and sphingomyelins (SMs). The levels of plasma CEs, LPCs, PCs, SMs, and CERs were significantly increased in the HFD group compared to those in the ND group, and levels of these lipids recovered to normal after administration of CLE or LU. Furthermore, changes in hepatic mRNA expression levels involved in the Kennedy pathway and sphingolipid biosynthesis were also suppressed by treatment with CLE or LU. In conclusion, this study examined the beneficial effects of CLE and LU on obesity and dyslipidemia, which were demonstrated as reduced synthesis of lipotoxic intermediates. These results may provide valuable insights towards evaluating the therapeutic effects of CLE and LU and understanding obesity-related diseases.
Highlights
Obesity, one of the major worldwide health problems in recent years, is usually caused by an imbalance in food intake and energy expenditure, with overconsumption of energy intake or decreaseNutrients 2020, 12, 2973; doi:10.3390/nu12102973 www.mdpi.com/journal/nutrientsNutrients 2020, 12, 2973 in physical activity
We investigated the pharmacological effects of CM leaf extract (CLE) and luteolin, which are closely related to the physiological functions and quality of Chrysanthemum morifolium Ramat (CM) [27], and its mechanisms against high-fat diet (HFD)-induced dyslipidemia through alterations of plasma lipid metabolites using the technique of liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS)
The values of body weight, liver weight, total adipose tissue weight, and total cholesterol were 28.1 ± 1.4 g, 1.0 ± 0.1 g, 1.8 ± 0.2 g, and 4.1 ± 0.6 mmol/L in the normal diet (ND) group, respectively; due to administration of HFD, these levels were significantly elevated to 46.6 ± 1.5 g, 2.8 ± 0.3 g, 7.7 ± 0.6 g, and 7.8 ± 1.7 mmol/L respectively, indicating that the obese mouse model was well-established
Summary
One of the major worldwide health problems in recent years, is usually caused by an imbalance in food intake and energy expenditure, with overconsumption of energy intake or decrease. HFD-induced obesity is characterized by abnormally high levels of blood lipids, such as cholesterol, low-density lipoprotein (LDL), and triacylglycerol (TAG), leading to progressive weight gain in various tissues of the body (e.g., liver and fat tissues) due to excess fat accumulation [1,2] It is associated with an increase in the prevalence and risk of metabolic syndrome-related diseases, including type 2 diabetes (T2D), dyslipidemia, cardiovascular diseases (CVD), hypertension, and fatty liver [3,4]. The CM flower extract has been shown to prevent hyperlipidemic fatty liver disease by increasing hepatic peroxisome proliferator-activated receptor (PPAR)-α expression in hyperlipidemic fatty liver disease caused by high-fat milk [12] Such beneficial effects have been reported in HFD-induced obese mice [13] and an alloxan-induced diabetes mellitus model [14]. We investigated the pharmacological effects of CLE and luteolin, which are closely related to the physiological functions and quality of CM [27], and its mechanisms against HFD-induced dyslipidemia through alterations of plasma lipid metabolites using the technique of liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS)
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