Patients undergoing Roux-en-Y gastric bypass(RYGB)surgery elicit striking loss of body weight. Anatomical restructuring of the gastrointestinal(GI) tract, leading to reduced caloric intake and changes in food preferen...Patients undergoing Roux-en-Y gastric bypass(RYGB)surgery elicit striking loss of body weight. Anatomical restructuring of the gastrointestinal(GI) tract, leading to reduced caloric intake and changes in food preference, are thought to be the primary drivers of weight loss in bariatric surgery patients. However, the mechanisms by which RYGB surgery causes a reduced preference for fatty foods remain elusive. In a recent report, Hankir et al described how RYGB surgery modulated lipid nutrient signals in the intestine of rats to blunt their craving for fatty food. The authors reported that RYGB surgery restored an endogenous fat-satiety signaling pathway, mediated via oleoylethanolamide(OEA), that was greatly blunted in obese animals. In RYGB rats, high fat diet(HFD) led to increased production of OEA that activated the intestinal peroxisome proliferation activator receptors-α(PPARα). In RYGB rats, activation of PPARα by OEA was accompanied by enhanced dopamine neurotransmission in the dorsal striatum and reduced preference for HFD. The authors showed that OEA-mediated signals to the midbrain were transmitted via the vagus nerve. Interfering with either the production of OEA in enterocytes, or blocking of vagal and striatal D1 receptors signals eliminated the decreased craving for fat in RYGB rats. These studies demonstrated that bariatric surgery led to alterations in the reward circuitry of the brain in RYGB rats and reduced their preference for HFD.展开更多
Inflammation plays a central role in development of cardiovascular pathology, and enhanced understanding of the innate immune response will help direct novel therapeutic strategies to address heart disease. Host defen...Inflammation plays a central role in development of cardiovascular pathology, and enhanced understanding of the innate immune response will help direct novel therapeutic strategies to address heart disease. Host defense peptides (HDPs)—hereunder defensins—exhibit antimicrobial, chemotactic, tissue healing and other key biological properties. Beta-defensin expression in whole-heart-homogenate has been reported in different species, and plasma alpha-defensins have been associated with cardiovascular morbidity and mortality. Still, the role of defensins in cardiac pathophysiology remains widely undetermined. Here, we show that a subset of rat-beta-defensins (rBDs) is constitutively expressed in the myocardium, and that their gene-expression level is influenced by systemic exposure to inflammatory mediators (highfat-diet and lipopolysaccharide). Using synthetic analogues of select rBD peptides, we evaluated the antimicrobial activity of these HDPs against clinically relevant pathogens and their ability as immunoregulatory compounds. We found that an innate myocardial response that involves rBDs is activated by highfat-diet feeding in rats, and that these HDPs influence monocyte migration-findings that suggest the peptides responding to exogenous danger-signals, and act within the context of a myocardial “first-line-of-defense”.展开更多
文摘Patients undergoing Roux-en-Y gastric bypass(RYGB)surgery elicit striking loss of body weight. Anatomical restructuring of the gastrointestinal(GI) tract, leading to reduced caloric intake and changes in food preference, are thought to be the primary drivers of weight loss in bariatric surgery patients. However, the mechanisms by which RYGB surgery causes a reduced preference for fatty foods remain elusive. In a recent report, Hankir et al described how RYGB surgery modulated lipid nutrient signals in the intestine of rats to blunt their craving for fatty food. The authors reported that RYGB surgery restored an endogenous fat-satiety signaling pathway, mediated via oleoylethanolamide(OEA), that was greatly blunted in obese animals. In RYGB rats, high fat diet(HFD) led to increased production of OEA that activated the intestinal peroxisome proliferation activator receptors-α(PPARα). In RYGB rats, activation of PPARα by OEA was accompanied by enhanced dopamine neurotransmission in the dorsal striatum and reduced preference for HFD. The authors showed that OEA-mediated signals to the midbrain were transmitted via the vagus nerve. Interfering with either the production of OEA in enterocytes, or blocking of vagal and striatal D1 receptors signals eliminated the decreased craving for fat in RYGB rats. These studies demonstrated that bariatric surgery led to alterations in the reward circuitry of the brain in RYGB rats and reduced their preference for HFD.
文摘研究鱼油对高脂模型小鼠血脂的改善作用。将6—7周龄雄性C57BL/6J小鼠分为三组,饲喂正常饮食、高脂饮食或高脂补充鱼油18周后,测定体重、食物摄入量、肝脏指数和空腹血糖,并用酶法检测血清中甘油三酯(Triglyceride,TG)、总胆固醇(total cholesterol,TC)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)浓度及游离脂肪酸(nonestesterified fatty acid,NEFA)含量。通过使用苏木精—伊红染色法及油红O染色法评价了肝组织形态学改变。结果表明,在高脂饮食小鼠中,体重增加,肝脏甘油三酯(TG)水平较正常小鼠高出约38%(P为0.0028);与高脂饮食小鼠相比,高脂补充鱼油的小鼠TG降低了6.80%(P为0.6738)、LDL-C降低了33.23%(P为0.0023),HDL-C水平显著性提升了51.25%,此外,高脂补充鱼油组小鼠表现出更大的代谢变化,脂肪堆积减少33%(P为0.1207)。这些结果表明鱼油补充对高脂饮食诱导脂代谢的有益影响,鱼油可能通过调节脂肪代谢来改善高脂饮食引起的肥胖,血脂异常的潜力,这一结果可以应用于预防肥胖的个性化营养。
文摘Inflammation plays a central role in development of cardiovascular pathology, and enhanced understanding of the innate immune response will help direct novel therapeutic strategies to address heart disease. Host defense peptides (HDPs)—hereunder defensins—exhibit antimicrobial, chemotactic, tissue healing and other key biological properties. Beta-defensin expression in whole-heart-homogenate has been reported in different species, and plasma alpha-defensins have been associated with cardiovascular morbidity and mortality. Still, the role of defensins in cardiac pathophysiology remains widely undetermined. Here, we show that a subset of rat-beta-defensins (rBDs) is constitutively expressed in the myocardium, and that their gene-expression level is influenced by systemic exposure to inflammatory mediators (highfat-diet and lipopolysaccharide). Using synthetic analogues of select rBD peptides, we evaluated the antimicrobial activity of these HDPs against clinically relevant pathogens and their ability as immunoregulatory compounds. We found that an innate myocardial response that involves rBDs is activated by highfat-diet feeding in rats, and that these HDPs influence monocyte migration-findings that suggest the peptides responding to exogenous danger-signals, and act within the context of a myocardial “first-line-of-defense”.
