与肥胖相关的骨桥蛋白和甲基化血液水平可通过极低热量生酮饮食或减肥手术进行差异调节

IF 6.6 2区医学 Q1 NUTRITION & DIETETICS

Clinical nutrition Pub Date : 2025-02-11 DOI:10.1016/j.clnu.2025.02.006

Paula M. Lorenzo , Andrea G. Izquierdo , Ignacio Sajoux , Maitane Nuñez-Garcia , Diego Gomez-Arbelaez , M. Angeles Zulet , Itziar Abete , Javier Baltar , Daniel de Luis , Francisco J. Tinahones , J. Alfredo Martinez , Felipe F. Casanueva , Ana B. Crujeiras

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引用次数: 0

摘要

背景,肌桥蛋白（OPN）被认为在肥胖和相关疾病（如癌症）的病理生理中发挥作用。目的是评估饮食性肥胖（DIO）动物模型中热量限制诱导的体重减轻后脂肪组织（AT）中OPN的表达，并将这些结果反映在肥胖（pvo）患者的循环OPN水平上；并探讨极低热量生酮饮食（VLCKD）对OPN循环蛋白和DNA甲基化水平的影响，与平衡低热量饮食（LCD）或减肥手术（BS）进行比较。方法在饮食性肥胖（DIO）小鼠的皮下（SAT）和内脏（VAT） AT以及4周的热量限制（CR）减肥方案中，评估sopn /SPP1的表达。对32名体重正常的志愿者（20名女性）和79名体重正常的志愿者（59名女性）进行了血浆OPN的评估，并对VLCKD （n = 20）、BS （n = 39）或LCD （n = 20）进行了4-6个月的随访。OPN的DNA甲基化水平从我们的Infinium HumanMethylation450 BeadChips数据集中提取。结果DIO小鼠VAT和pvo血浆中opn水平高于正常体重者，减重后发生变化。特别是，循环OPN在BS后2个月增加，而在VLCKD诱导的最大酮症时下降。VLCKD后cg11226901的甲基化水平也有统计学意义的降低。结论VLCKD后sopn水平降低，BS后sopn水平严重升高。因此，它可能是肥胖相关代谢应激的生物标志物，并可能受到表观遗传调控。

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Obesity-related osteopontin protein and methylation blood levels are differentially modulated by a very low-calorie ketogenic diet or bariatric surgery

Background & aim

Osteopontin (OPN) was proposed to play a role in the pathophysiology of obesity and related disease, such as cancer. The aims were to evaluate the expression of OPN after caloric restriction-induced weight loss in adipose tissue (AT) from an animal model of diet-induced obesity (DIO) and to reflect these results on circulating OPN levels in patients with obesity (PWO); and to explore the effect of a very low-calorie ketogenic diet (VLCKD) on the circulating protein and DNA methylation levels of OPN, compared with a balanced hypocaloric diet (LCD) or bariatric surgery (BS) in PWO.

Methods

OPN/SPP1 expression was evaluated in subcutaneous (SAT) and visceral (VAT) AT derived from diet-induced obesity (DIO) mice and after a 4-week weight-loss protocol of calorie restriction (CR). Plasmatic OPN was also evaluated in 32 normal-weight volunteers (20 women) and 79 PWO (59 women) and after a 4–6 months follow up of a VLCKD (n = 20), BS (n = 39) or LCD (n = 20). DNA methylation levels of OPN were extracted from our Infinium HumanMethylation450 BeadChips data sets.

Results

OPN levels were higher in VAT of DIO mice and plasma of PWO than in normal-weight individuals and changed after weight loss. Particularly, circulating OPN increased 2 months after BS while it decreased at maximum ketosis-induced by VLCKD. A statistically significant decrease was also observed in methylation levels at cg11226901 after VLCKD.

Conclusions

OPN levels were reduced after VLCKD and severely increased after BS. Therefore, it could be a biomarker of the obesity-related metabolic stress and could be epigenetically regulated.

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来源期刊

Clinical nutrition 医学-营养学

CiteScore

14.10

自引率

6.30%

发文量

356

审稿时长

28 days

期刊介绍： Clinical Nutrition, the official journal of ESPEN, The European Society for Clinical Nutrition and Metabolism, is an international journal providing essential scientific information on nutritional and metabolic care and the relationship between nutrition and disease both in the setting of basic science and clinical practice. Published bi-monthly, each issue combines original articles and reviews providing an invaluable reference for any specialist concerned with these fields.