High-fat, high-sugar diet (HFHS) induced leptin resistance and intestinal epithelial dysfunction is implicated in hyperphagia and metabolic disorders. Numerous studies have demonstrated the efficacy of dietary interventions for reducing appetite. This study aims to investigate whether triacylglycerol rich in DHA (DHA-TG) could regulate appetite in mice fed with a HFHS diet and the mechanism by which it achieves that. DHA-TG could reduce food intake and regulate neuropeptides (POMC, AgRP, and NPY) expression in HFHS diet-fed mice. Hypothalamic transcriptome analysis reveals that these effects might be attributed to the role of DHA-TG in modulating hormone secretion and digestive system process. According to ELISA and RT-qPCR analysis, DHA-TG ameliorated leptin secretion and attenuated central leptin resistance induced by HFHS diet feeding. Besides, DHA-TG prevented the damage of intestinal epithelial barrier in nutritive obese mice by improving leptin sensitivity. Based on jejunal transcriptome analysis, DHA-TG also protected intestinal endocrine function, especially the secretion of another anorectic hormone, cholecystokinin (CCK), in HFHS diet-fed mice. Furthermore, DHA-TG was ineffective in repressing appetite, and improving gut leakage in leptin-deficient mice (ob/ob mice). In conclusion, DHA-TG has a potential to regulate appetite with the action of leptin, and intestinal epithelial functions in HFHS diet-fed mice.

高脂肪、高糖饮食 (HFHS) 诱导的瘦素抵抗和肠上皮功能障碍与食欲过盛和代谢紊乱有关。许多研究已经证明了饮食干预对降低食欲的功效。本研究旨在调查富含 DHA (DHA-TG) 的三酰基甘油是否可以调节喂食 HFHS 饮食的小鼠的食欲，以及它实现这一目标的机制。DHA-TG 可以减少 HFHS 饮食喂养小鼠的食物摄入并调节神经肽（POMC、AgRP 和 NPY）的表达。下丘脑转录组分析表明，这些作用可能归因于 DHA-TG 在调节激素分泌和消化系统过程中的作用。根据 ELISA 和 RT-qPCR 分析，DHA-TG 改善了瘦素分泌并减弱了 HFHS 饮食喂养诱导的中枢瘦素抵抗。除了，DHA-TG通过提高瘦素敏感性来预防营养性肥胖小鼠肠上皮屏障的损伤。根据空肠转录组分析，DHA-TG 还可以保护 HFHS 饮食喂养小鼠的肠道内分泌功能，尤其是另一种厌食激素胆囊收缩素 (CCK) 的分泌。此外，DHA-TG 在抑制食欲和改善瘦素缺陷小鼠（ob/ob 小鼠）的肠道渗漏方面无效。总之，DHA-TG 有可能通过瘦素的作用调节食欲，以及 HFHS 饮食喂养小鼠的肠上皮功能。胆囊收缩素 (CCK)，在 HFHS 饮食喂养的小鼠中。此外，DHA-TG 在抑制食欲和改善瘦素缺陷小鼠（ob/ob 小鼠）的肠道渗漏方面无效。总之，DHA-TG 有可能通过瘦素的作用调节食欲，以及 HFHS 饮食喂养小鼠的肠上皮功能。胆囊收缩素 (CCK)，在 HFHS 饮食喂养的小鼠中。此外，DHA-TG 在抑制食欲和改善瘦素缺陷小鼠（ob/ob 小鼠）的肠道渗漏方面无效。总之，DHA-TG 有可能通过瘦素的作用调节食欲，以及 HFHS 饮食喂养小鼠的肠上皮功能。