Gut microbiota regulate the activation of adipose browning, which promote energy dissipation and combat diet-induced obesity. Pomegranate peel polyphenols (PPPs) have been shown to reduce obesity, regulate lipid metabolism in adipose tissue, and modulate the composition of gut microbiota in animal fed high-fat diet (HFD). However, the role of gut microbiota in the improvement of obesity by PPPs has not been elucidated. In current study, we applied antibiotics to inhibit gut microbiota in mice fed HFD and treated with PPPs. The results showed that the inhibition of gut microbiota impair the effect of PPPs on reducing obesity and promoting adipose browning, and change the fecal metabolomic profiles in respond to PPPs. Moreover, the inhibition of gut microbiota supressed the promotive effects of PPPs on the levels of Akkermansia and microbiota-related metabolites, such as urolithin A, short-chain fatty acids (SCFAs), and bile acids (BAs), which were associated with activating adipose browning. Therefore, our results suggested that the presence of gut microbiota is essential for PPPs to ameliorate HFD-induced obesity. The related bacteria or metabolites generated by the interaction between PPPs and microbiota promote adipose browning and facilitate the beneficial effects of PPPs.

The high incidence of postpartum hypogalactia hinders the healthy development of postpartum women and the next generation. Lacquer seed oil (LSO), the oil extracted from the seeds of the lacquer tree, has been traditionally used as a dietary supplement for promoting postpartum lactation and recovery in some districts of China. However, its physiological effects have not been verified, and the mechanism and active components of LSO have not been analyzed. Thus, we applied LSO to bromocriptine-induced postpartum hypogalactia rats. The results showed that LSO supplement effectively improves bromocriptine-induced postpartum hypogalactia. LSO also increased prolactin levels reduced by bromocriptine, promoted JAK2/STAT5 and PI3K/AKT pathways and several gene expression levels of milk synthesis in mammary gland. Moreover, metabolomic and network pharmacological analysis further revealed that JAK2/STAT5, PI3K/AKT, and estrogen signaling pathway are the potential main regulatory sites for the beneficial effects of LSO on postpartum hypogalactia, and that quercetin, kaempferol, arachidonic acid, epicatechin, and β-sitosterol are the top 5 main active ingredients of LSO. Our results suggested that LSO has great potential in the application of the improvement of postpartum hypogalactia.

Insulin resistance (IR) has been considered to be an important causative factor of metabolic syndrome (MetS). The present study investigated whether pomegranate peel polyphenols (PPPs) could prevent the development of MetS by improving IR in rats. Male Sprague-Dawley (SD) rats were fed high fat diet (HFD) to induce MetS and supplemented with different dosages of PPPs for 12 weeks. The results showed that HFD-induced insulin resistant rats had disordered metabolism of blood glucose, blood lipid, and terrible muscle fiber morphology when compared with normal diet-fed rats, but PPPs treatment at a dosage of 300 mg/kg·day significantly reversed these negative effects. Moreover, in skeletal muscle tissue of insulin resistant rats, PPPs treatments significantly increased the protein expressions of insulin receptor (InsR) and phosphorylated insulin receptor substrate 1 (IRS-1), stimulated peroxisome proliferator activated receptor gamma (PPARγ) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT/PKB) signaling pathway, and aggrandized the protein levels of phosphorylated glycogen synthase kinase-3β (GSK-3β) and glucose transporter 4 (GLUT4). Our results suggest that PPPs possess of the beneficial effects on alleviating IR by enhancing insulin sensitivity and regulating glucose metabolism.