hydroxysafflor-yellow-a and Obesity

Our previous studies found that safflower yellow (SY) and its main component hydroxysafflor yellow A (HSYA) could alleviate obesity and improve leptin resistance in high-fat diet (HFD) induced obese mice. Therefore, our present study aimed to investigate whether the above effect of SY/HSYA was a direct effect or follow-up effect of weight loss and whether leptin was essential for the anti-obesity effect of SY/HSYA or not. HFD-induced obese mice were treated with SY or HSYA for 4 weeks, while ob/ob mice were treated with SY for 10 weeks. Body weight, food intake, fat mass, and serum leptin levels were measured. The leptin sensitivity experiment was conducted in HFD-induced obese mice. The expressions of leptin and its signaling-related genes were detected by RT-qPCR and Western blot methods. SY/HSYA treatment had no effect on food intake, energy expenditure, body weight, fat mass, and serum leptin levels in HFD-induced obese mice. However, the leptin sensitivity experiment showed that the food intake decreased by 18.4% in the HFD-SY group and the body weight gain decreased by 104.6% in the HFD-HSYA group, respectively (both P < 0.05). Furthermore, the expressions of leptin and leptin signaling inhibitory regulators were significantly decreased, while the phosphorylation of signal transducer and activator of transcription 3 (p-STAT3) were notably increased in WAT of HFD-induced obese mice, fully differentiated 3T3-L1 adipocytes after SY/HSYA intervention (all P < 0.05). Interestingly, SY treatment was ineffective on body weight, fat mass, and glucose metabolism in leptin-deficient ob/ob mice. SY/HSYA administration could firstly improve peripheral leptin resistance in adipose tissue of HFD-induced obese mice before their body weight was significantly changed, and leptin was essential for the anti-obesity effect of SY.

Topics: Animals; Body Weight; Chalcone; Diet, High-Fat; Leptin; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Quinones

Given the high and increasing prevalence of obesity, the safe and effective treatment of obesity would be beneficial. Here, we examined whether oral hydroxysafflor yellow A (HSYA), an active compound from the dried florets of Carthamus tinctorius L., can reduce high-fat (HF) diet-induced obesity in C57BL/6 J mice. Our results showed that the average body weight of HF group treated by HSYA was significantly lower than that of the HF group (P < 0.01). HSYA also reduced fat accumulation, ameliorated insulin resistance, restored glucose homeostasis, reduced inflammation, enhanced intestinal integrity, and increased short-chain fatty acids (SCFAs) production in HF diet-fed mice. Sequencing of 16S rRNA genes in fecal samples demonstrated that HSYA reversed HF diet induced gut microbiota dysbiosis. Particularly, HSYA increased the relative abundances of genera Akkermansia and Romboutsia, as well as SCFAs-producing bacteria, including genera Butyricimonas and Alloprevotella, whereas it decreased the phyla Firmicutes/Bacteroidetes ratio of HF diet-fed mice. Additionally, serum metabolomics analysis revealed that HSYA increased lysophosphatidylcholines (lysoPCs), L-carnitine and sphingomyelin, and decreased phosphatidylcholines in mice fed a HF diet, as compared to HF group. These changed metabolites were mainly linked with the pathways of glycerophospholipid metabolism and sphingolipid metabolism. Spearman's correlation analysis further revealed that Firmicutes was positively while Bacteroidetes and Akkermansia were negatively correlated with body weight, fasting serum glucose and insulin. Moreover, Akkermansia and Butyricimonas had positive correlations with lysoPCs, suggestive of the role of gut microbiota in serum metabolites. Our findings suggest HSYA may be a potential therapeutic drug for obesity and the gut microbiota may be potential territory for targeting of HSYA.

Topics: Adiposity; Administration, Oral; Animals; Anti-Obesity Agents; Bacteria; Biomarkers; Blood Glucose; Chalcone; Diet, High-Fat; Disease Models, Animal; Energy Metabolism; Fatty Acids, Volatile; Gastrointestinal Microbiome; Insulin; Insulin Resistance; Intestines; Male; Metabolomics; Mice, Inbred C57BL; Obesity; Quinones; Weight Loss