Research On Mechanisms Of Eliminating Obesity By Luteolin Based On Circadian Rhythm

The circadian clocks control daily oscillation of many physiological processes,including feeding behavior,lipid/carbohydrate metabolism,and sleep.The circadian clock and obesity are intimately interconnected.During the development of diet-induced obesity,overnutrition affects oscillations and expressions of circadian clock genes and clock-controlled genes in peripheral tissues.The dysfunction of circadian clock increases the capacity of the adipocyte for triglyceride storage and finally leads to obesity.Luteolin?LU?can induce adipose tissue browning and thermogenesis resulting in weight loss.However,the effect of circadian rhythms on this process remains unclear.PPAR?/RXR?/FGF21 pathway may as a molecular link between circadian rhythm and energy metabolism,however,little is known as to whether PPAR?/RXR?/FGF21 signaling is involved in the process of LU-activated adipocyte browning.Chrysanthemum morifolium Ramat.?Chr?is a notable medicinal and edible crop that contains its main active flavonoid luteolin,and is considered a health food due to its biological effects,such as decreasing free radicals,ameliorating cardiovascular disorders,reducing inflammation,lowering blood glucose,and losing body weight.The effective classication of Chr cultivars and determination of luteolin content in Chr are important subjects for guiding the medicinal application of Chr and luteolin.Notably,multispectral imaging system?MSI?covers the electromagnetic wave from visible light to near-infrared ray and can realize the rapid and non-destructive detection of samples,which has great guiding significance and theoretical value for identification of chr and determination of luteolin content.This study provides a new theory for rapid and non-destructive test of food and treatment of obesity.The main results were as follows:1.Dietary luteolin induces adipose tissue browning in wild-type mice through rhythmically increasing hepatic PPAR?/RXR?/FGF21 pathway.Luteolin?LU?induced circadian entrainment of energy expenditure by increasing rhythmic expression of UCP1 and metabolically related genes,accompanied by ameliorating daily rhythms in core clock genes disrupted by high-fat diet?HFD?in metabolic tissues in wild-type?WT?mice.PPAR?/RXR?/FGF21 signaling in liver,the critical participation in LU-regulated metabolic and rhythm disorders,exhibited higher levels and more powerful circadian rhythmicity by dietary LU,resulting in activation of adipose tissue browning.2.Deficiency of Per2 blocks luteolin-activated adipose tissue browning in mice through weakening hepatic PPAR?/RXR?/FGF21 pathway.Luteolin?LU?did not affect diet-induced obesity and metabolic disorders in Per2^-/-mice.UCP1 expressions in adipose tissue were not changed by dietary LU in HFD-fed Per2^-/-mice.Strikingly,Loss of Per2 led to the less change of PPAR?,RXR?,and FGF21 diurnal levels by dietary LU.In vitro,LU treatment directly activated PPAR?/RXR?/FGF21 signaling in primary cultured hepatocytes from WT mice rather than Per2^-/-mice.Taken together,deletion of the core clock component Per2 impedes LU-induced adipose tissue browning through weakening hepatic PPAR?/RXR?/FGF21 pathway in mice.3.Discrimination of cultivars and determination of luteolin content of Chrysanthemum morifolium Ramat.A combination of MSI with principal component analysis?PCA?and least squares-support vector machines?LS-SVM?were applied to classify Chr cultivars.PCA derived from the spectral and morphological features data of the samples explained 99.61%for summing up the first three principal components and the LS-SVM model achieved 98%discrimination accuracy in the prediction set.Additionally,partial least squares?PLS?and LS-SVM models were obtained to predict performance for luteolin content determination,with Rp of 0.949 and 0.965,RMSEP of 0.387 and 0.314 mg/g,respectively.All results demonstrated that the combination of MSI system with chemometrics methods could be a rapid and non-destructive method to discriminate between Chr cultivars and determine luteolin content in Chr.