African cactiform Hoodia gordonii (Asclepiadaceae) has been used for thousands of years by Xhomani Bushmen as an anorexant during hunting trips and has been proposed as a new agent for the management of body weight. However, its in vivo targets and molecular mechanisms remain elusive. GPR119, a G protein-coupled receptor highly expressed in pancreatic β cells and intestinal L cells, has been demonstrated to facilitate glucose-stimulated insulin secretion (GSIS) and represents a novel and attractive target for the therapy of metabolic disorders. Here, we disclose that Gordonoside F (a steroid glycoside isolated from H. gordonii), but not the widely known P57, activates specifically GPR119. Successful synthesis of Gordonoside F facilitates further characterization of this compound. Gordonoside F promotes GSIS both in vitro and in vivo and reduces food intake in mice. These effects are mediated by GPR119 because GPR119 knockout prevents the therapeutic effects of Gordonoside F. Interestingly, the appetite-suppressing effect of Hoodia extract was also partially blocked by GPR119 knockout. Our results demonstrate for the first time, to our knowledge, that GPR119 is a direct target and one of the major mechanisms underlying the therapeutic effect of the popular "weight loss" herb H. gordonii. Given the long history of safe application of this herb in weight control, it is foreseeable that the novel scaffold of Gordonoside F provides a promising opportunity to develop new drugs in treating metabolic diseases.

Simple SummaryMannan oligosaccharides (MOS) are a promising feed additive to improve animal health, immune capacity, and antioxidation. Based on the previous studies, we carried out three experiments to investigate the effects of MOS on the gas emission, protein and energy utilization, and fasting metabolism of sheep. The results showed that 2.0% MOS supplementation led to the lowest in vitro CO2 production and lower CH4 production and decreased in vivo intake. However, it also decreased urine nitrogen excretion and energy released as CH4, and then improved the utilization of crude protein and energy of sheep. There were no differences in the parameters of respiration and energy metabolism of sheep under the fasting condition. The findings indicated that MOS slightly affected the gas emission and nutrients and energy utilization of sheep.AbstractThis study investigated the effects of mannan oligosaccharides (MOS) on in vitro and in vivo gas emission, utilization of crude protein (CP) and energy, and relative parameters of sheep under fasting metabolism conditions. In vitro gas productions were evaluated over 12 h in sheep diets containing different amounts of MOS (from 0% to 6.0%/kg, the increment was 0.5%). A control experiment was used to assess the gas emission, utilization of CP and energy, and fasting metabolism in control sheep and sheep treated with 2.0% MOS over 24 days (d). The results showed that 2.0% MOS supplementation led to the lowest in vitro CO2 production and less CH4 production, while also leading to decrease in vivo nutrients intake, CP and energy excretion, digested and retained CP, and energy released as CH4 (p < 0.05). Furthermore, 2.0% MOS supplementation appeared to decrease in vivo O2 consumption and CH4 production per metabolic body weight (BW0.75), and increase the CP retention rate of sheep (p < 0.074). MOS did not affect other parameters, along with the same parameters of sheep under fasting metabolism conditions (p > 0.05). The findings indicate MOS has only slight effects on the gas emission and nutrients and energy metabolism of sheep.