Adipocyte-Derived PXR Signaling Is Dispensable for Diet-Induced Obesity and Metabolic Disorders in Mice.

Pregnane X receptor (PXR) is a xenobiotic receptor that can be activated by numerous chemicals including endogenous hormones, dietary steroids, pharmaceutical agents, and environmental chemicals. PXR has been established to function as a xenobiotic sensor to coordinately regulate xenobiotic metabolism by regulating the expression of many enzymes and transporters required for xenobiotic metabolism. Recent studies have implicated a potentially important role for PXR in obesity and metabolic disease beyond xenobiotic metabolism, but how PXR action in different tissues or cell types contributes to obesity and metabolic disorders remains elusive. To investigate the role of adipocyte PXR in obesity, we generated a novel adipocyte-specific PXR deficient mouse model (PXRΔAd). Notably, we found that loss of adipocyte PXR did not affect food intake, energy expenditure, and obesity in high-fat diet-fed male mice. PXRΔAd mice also had similar obesity-associated metabolic disorders including insulin resistance and hepatic steatosis as control littermates. PXR deficiency in adipocytes did not affect expression of key adipose genes in PXRΔAd mice. Our findings suggest that adipocyte PXR signaling may be dispensable in diet-induced obesity and metabolic disorders in mice. Further studies are needed to understand the role of PXR signaling in obesity and metabolic disorders in the future. SIGNIFICANCE STATEMENT: The authors demonstrate that deficiency of adipocyte pregnane X receptor (PXR) does not affect diet-induced obesity or metabolic disorders in mice and infers that adipocyte PXR signaling may not play a key role in diet-induced obesity. More studies are needed to understand the tissue-specific role of PXR in obesity.

Active Tumor-Targeted co-Delivery of Epigallocatechin Gallate and Doxorubicin in Nanoparticles for Combination Gastric Cancer Therapy.

The clinical treatment of gastric cancer is hampered by the development of anticancer drug resistance as well as the unfavorable pharmacokinetics, nontarget toxicity, and inadequate intratumoral accumulation of current chemotherapies. The polyphenol epigallocatechin gallate in combination with doxorubicin exhibits synergistic inhibition P-glycoprotein efflux pump activity and cancer cell growth. This study evaluated a potential activated nanoparticle delivery system comprising a hyaluronic acid complex with polyethylene glycol-conjugated gelatin containing encapsulated epigallocatechin gallate and low-dose doxorubicin, which may facilitate targeted drug administration to gastric cancer cells. We confirmed successful delivery of bioactive combination drugs and internalization into gastric cancer cells through CD44 ligand recognition and ensuing inhibition of cell proliferation via caspase-induced apoptosis and G2/M phase cell cycle arrest. Furthermore, the targeted nanoparticles significantly suppressed gastric tumor activity and reduced both tumor and heart tissue inflammatory reaction in vivo compared to systemic combination treatment.