Álvarez-Loredo Héctor Edmundo, Layseca-Espinosa Esther, Victoria-Campos Claudia Inés, Hernández-Mendoza Héctor, Chávez-Prieto Estefanía, Rios-Lugo María Judith
Posgrado de Ciencias Biomédicas Básicas, Facultad de Medicina, Universidad Autónoma de San Luis Potosí, Av. Venustiano Carranza 2405, San Luis Potosí, S.L.P, CP 78210, México.
Sección de Medicina Molecular y Traslacional, Centro de Investigación en Ciencias de la Salud y Biomedicina, Universidad Autónoma de San Luis Potosí, Avda. Sierra Leona 550, San Luis Potosí, S.L.P, CP 78210, México.
Hormones (Athens). 2025 Sep 17. doi: 10.1007/s42000-025-00717-4.
Obesity, characterized by excessive fat accumulation, disrupts metabolism, leading to insulin resistance, hyperglycemia, and dyslipidemia. Circadian rhythm genes such as BMAL1 and CRY1 regulate energy balance, lipid metabolism, and glucose homeostasis, with enzymes, for example, DGAT1 and DGAT2, playing critical roles in triglyceride synthesis. Melatonin, a circadian regulator, influences metabolic processes, including glucose and insulin regulation. This study examined melatonin's therapeutic effects in obese Wistar rats. A total of 48 male rats were fed either a standard diet (C group) or a high-fat diet for 11 weeks to induce obesity. Once the obese group was established, the latter animals were subdivided into two experimental groups, namely, OB (obesity-induced) and OB-M (obesity-induced + melatonin), each under two circadian shifts (9 h and 21 h). During the subsequent 6 weeks, all animals received standard diets plus/minus melatonin supplementation (25 µg/mL in drinking water). The 9 h and 21 h time points were selected to evaluate the effects of circadian rhythm alignment or disruption on metabolic outcomes and melatonin efficacy. Body weight, food intake, and water consumption were recorded every third day. Melatonin supplementation significantly reduced body weight in OB-M group, with no effect observed in the control animals. It also improved glucose, cholesterol, and triglyceride levels compared to diet change alone. Leptin and IL-1β levels decreased with melatonin, suggesting anti-inflammatory and metabolic regulatory effects. Additionally, melatonin influenced circadian gene expression, including BMAL1 and CRY1, and showed correlations with metabolic and inflammatory markers. These findings indicate that melatonin supplementation, when combined with dietary modifications, improves metabolic outcomes and contributes to the restoration of circadian and inflammatory balance in obesity. However, further research is required to elucidate the underlying mechanisms.
肥胖以脂肪过度堆积为特征，会扰乱新陈代谢，导致胰岛素抵抗、高血糖和血脂异常。诸如BMAL1和CRY1等昼夜节律基因调节能量平衡、脂质代谢和葡萄糖稳态，而酶（例如二酰甘油酰基转移酶1和二酰甘油酰基转移酶2）在甘油三酯合成中起关键作用。褪黑素作为一种昼夜节律调节因子，会影响包括葡萄糖和胰岛素调节在内的代谢过程。本研究考察了褪黑素对肥胖Wistar大鼠的治疗作用。总共48只雄性大鼠被喂食标准饮食（C组）或高脂饮食11周以诱导肥胖。肥胖组建立后，将后一组动物再细分为两个实验组，即OB（肥胖诱导组）和OB-M（肥胖诱导+褪黑素组），每组处于两种昼夜节律变化（9小时和21小时）条件下。在随后的6周内，所有动物接受标准饮食并加/减褪黑素补充剂（饮用水中含25μg/mL）。选择9小时和21小时这两个时间点来评估昼夜节律调整或紊乱对代谢结果和褪黑素疗效的影响。每隔三天记录体重、食物摄入量和饮水量。补充褪黑素显著降低了OB-M组的体重，而对照动物未观察到效果。与仅改变饮食相比，它还改善了葡萄糖、胆固醇和甘油三酯水平。瘦素和白细胞介素-1β水平随褪黑素降低，表明具有抗炎和代谢调节作用。此外，褪黑素影响昼夜节律基因表达，包括BMAL1和CRY1，并与代谢和炎症标志物存在相关性。这些发现表明，补充褪黑素并结合饮食调整可改善代谢结果，并有助于恢复肥胖状态下的昼夜节律和炎症平衡。然而，需要进一步研究以阐明其潜在机制。
