N-oleoylglycine (OlGly), a lipid derived from the basic component of olive oil, oleic acid, and N-oleoylalanine (OlAla) are endocannabinoid-like mediators. We report that OlGly and OlAla, by activating the peroxisome proliferator-activated receptor alpha (PPARα), reduce the rewarding properties of a highly palatable food, dopamine neuron firing in the ventral tegmental area, and the obesogenic effect of a high-fat diet rich in lard (HFD-L). An isocaloric olive oil HFD (HFD-O) reduced body weight gain compared to the HFD-L, in a manner reversed by PPARα antagonism, and enhanced brain and intestinal OlGly levels and gut microbial diversity. OlGly or OlAla treatment of HFD-L mice resulted in gut microbiota taxonomic changes partly similar to those induced by HFD-O. We suggest that OlGly and OlAla control body weight by counteracting highly palatable food overconsumption, and possibly rebalancing the gut microbiota, and provide a potential new mechanism of action for the obeso-preventive effects of olive oil-rich diets.

N-油酰甘氨酸 (OlGly) 是一种源自橄榄油基本成分的脂质，油酸和N-油酰丙氨酸 (OlAla) 是内源性大麻素样介质。我们报告说，OlGly 和 OlAla 通过激活过氧化物酶体增殖物激活受体 α (PPARα)，降低了高度适口食物的奖励特性、腹侧被盖区的多巴胺神经元放电以及富含高脂肪饮食的肥胖效应。猪油（HFD-L）。与 HFD-L 相比，等热量橄榄油 HFD (HFD-O) 可通过 PPARα 拮抗作用逆转体重增加，并增强大脑和肠道 OlGly 水平以及肠道微生物多样性。OlGly 或 OlAla 治疗 HFD-L 小鼠导致肠道微生物群分类学变化，部分类似于 HFD-O 引起的变化。我们认为 OlGly 和 OlAla 通过抵消高适口食物的过度消费来控制体重，并可能重新平衡肠道微生物群，并为富含橄榄油的饮食的肥胖预防作用提供潜在的新作用机制。