Epigenomics in Endocrinology and Nutrition Group, Instituto de Investigacion Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS/SERGAS), Spain; CIBER de Fisiopatologia de La Obesidad y Nutricion (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain.
Epigenomics in Endocrinology and Nutrition Group, Instituto de Investigacion Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS/SERGAS), Spain; Medical Department Pronokal Group, Barcelona, Spain.
Clin Nutr. 2022 Jul;41(7):1566-1577. doi: 10.1016/j.clnu.2022.05.007. Epub 2022 May 18.
BACKGROUND & AIM: Inflammation and oxidative stress are the most probable mechanistic link between obesity and its co-diseases with cancer among them. The aim of this study was to evaluate whether the nutritional ketosis and weight loss induced by a very-low-calorie ketogenic diet (VLCKD) modulates the inflammatory and oxidative stress profile, compared with a standard, balanced hypocaloric diet (LCD) or bariatric surgery (BS) in patients with obesity.
The study was performed in 79 patients with overweight or obesity and 32 normal-weight volunteers as the control group. Patients with obesity underwent a weight reduction therapy based on VLCKD, LCD or BS. The quantification of the circulating levels of a multiplexing test of cytokines and carcinogenesis/aging biomarkers, as well as of lipid peroxides and total antioxidant power, was carried out.
First, we observed that pro-inflammatory cytokines increase, while anti-inflammatory cytokines decrease under excessive body weight. Relevantly, when patients underwent weight loss strategies, it was shown that energy-restricted and surgical strategies of weight loss induced changes in circulating cytokine and lipid peroxides. This effect was more notable in patients following the VLCKD than the LCD or BS and it was observed mainly in the ketosis phase of the intervention. Particularly, IL-11, IL-12, IL-2, INF-γ, INF-β, Pentraxin-3 or MMP1 changed after VLCKD. Whereas, APRIL, TWEAK, osteocalcin and IL-28A increased after BS.
As far as we know, this is the first study that evaluate the time-course of cytokines and oxidative stress markers after a VLCKD as compared with a standard LCD and BS. The observed results support the immunomodulatory effect of nutritional ketosis induced by a VLCKD synergistically with weight loss as a strategy to improve innate-immunity and to prevent infections and carcinogenesis in patients with obesity.
炎症和氧化应激是肥胖及其合并症（包括癌症）之间最可能的机制联系。本研究旨在评估极低卡路里生酮饮食（VLCKD）诱导的营养性酮症和体重减轻与标准平衡低热量饮食（LCD）或减重手术（BS）相比，是否能调节肥胖患者的炎症和氧化应激谱。
该研究纳入了 79 名超重或肥胖患者和 32 名正常体重志愿者作为对照组。肥胖患者接受了基于 VLCKD、LCD 或 BS 的减重治疗。通过多重分析检测试剂盒检测细胞因子和致癌/衰老生物标志物以及脂质过氧化物和总抗氧化能力的循环水平。
首先，我们观察到超重状态下促炎细胞因子增加，而抗炎细胞因子减少。相关地，当患者进行减肥策略时，发现能量限制和手术减肥策略会引起循环细胞因子和脂质过氧化物的变化。与 LCD 或 BS 相比，VLCKD 引起的这种变化更为明显，并且主要发生在干预的酮症阶段。特别地，IL-11、IL-12、IL-2、INF-γ、INF-β、Pentraxin-3 或 MMP1 在 VLCKD 后发生变化。而 APRIL、TWEAK、骨钙素和 IL-28A 在 BS 后增加。
据我们所知，这是第一项评估 VLCKD 与标准 LCD 和 BS 相比后细胞因子和氧化应激标志物时间过程的研究。观察到的结果支持 VLCKD 诱导的营养性酮症的免疫调节作用，作为一种协同减轻体重的策略，改善肥胖患者的固有免疫，预防感染和癌症发生。
