Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain; Unidad de Gestión Clínica de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Málaga, Spain.
Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, Málaga, Spain; Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Regional Universitario, Málaga, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas-CIBERDEM, Málaga, Spain.
Pharmacol Res. 2023 Jan;187:106579. doi: 10.1016/j.phrs.2022.106579. Epub 2022 Nov 23.
The effect of oleic acid (OA) on the regulation of the circadian rhythm present in human visceral (VAT) and subcutaneous (SAT) adipose tissue from patients with morbid obesity has not been analyzed yet. VAT and SAT explants from patients with morbid obesity were incubated with OA to analyze the circadian regulation of clock and other genes related to lipid metabolism (SREBP-1c, FAS, LPL and CPT1), and their association with baseline variables and the improvement of these patients after bariatric surgery. There were significant differences in amplitude and acrophase in VAT with respect to SAT. In VAT, body weight negatively correlated with BMAL1 and CRY1 amplitude, and REVERBα acrophase; body mass index (BMI) negatively correlated with REVERBα acrophase; and waist circumference negatively correlated with PER3 acrophase. In SAT, BMI negatively correlated with CLOCK amplitude, and CLOCK, REVERBα and CRY2 MESOR; and waist circumference negatively correlated with PER3 amplitude and acrophase. A greater short-term improvement of body weight, BMI and waist circumference in patients with morbid obesity after bariatric surgery was associated with a lower CRY1 and CRY2 amplitude and an earlier PER1 and PER3 acrophase in SAT. OA produced a more relevant circadian rhythm and increased the amplitude of most clock genes and lipid metabolism-related genes. OA regulated the acrophase of most clock genes in VAT and SAT, placing CLOCK/BMAL1 in antiphase with regard to the other genes. OA increased the circadian rhythmicity, although with slight differences between adipose tissues. These differences could determine its different behavior in obesity.
尚未分析油酸(OA)对病态肥胖患者内脏(VAT)和皮下(SAT)脂肪组织中昼夜节律调节的影响。用 OA 孵育病态肥胖患者的 VAT 和 SAT 外植体,以分析时钟和其他与脂质代谢相关的基因(SREBP-1c、FAS、LPL 和 CPT1)的昼夜节律调节,及其与基线变量的相关性以及这些患者在减重手术后的改善情况。VAT 与 SAT 相比,振幅和高峰时间存在显著差异。在 VAT 中,体重与 BMAL1 和 CRY1 振幅呈负相关,与 REVERBα 高峰时间呈负相关;体重指数(BMI)与 REVERBα 高峰时间呈负相关;腰围与 PER3 高峰时间呈负相关。在 SAT 中,BMI 与 CLOCK 振幅和 CLOCK、REVERBα 和 CRY2 平均值呈负相关;腰围与 PER3 振幅和高峰时间呈负相关。病态肥胖患者在减重手术后短期内体重、BMI 和腰围的改善更大,与 SAT 中 CRY1 和 CRY2 振幅降低以及 PER1 和 PER3 高峰时间提前有关。OA 产生了更相关的昼夜节律,增加了大多数时钟基因和与脂质代谢相关基因的振幅。OA 调节了 VAT 和 SAT 中大多数时钟基因的高峰时间,使 CLOCK/BMAL1 与其他基因呈反相。OA 增加了昼夜节律性,尽管脂肪组织之间存在细微差异。这些差异可能决定了其在肥胖中的不同行为。