Calorie restriction improves lipid-related emerging cardiometabolic risk factors in healthy adults without obesity: Distinct influences of BMI and sex from CALERIE™ a multicentre, phase 2, randomised controlled trial.
Calorie restriction improves lipid-related emerging cardiometabolic risk factors in healthy adults without obesity: Distinct influences of BMI and sex from CALERIE™ a multicentre, phase 2, randomised controlled trial.
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DOI：
10.1016/j.eclinm.2021.101261
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发表时间：
2022-01
影响因子：
15.1
通讯作者：
CALERIE™ Investigators
中科院分区：
文献类型：
--
作者：
Huffman KM;Parker DC;Bhapkar M;Racette SB;Martin CK;Redman LM;Das SK;Connelly MA;Pieper CF;Orenduff M;Ross LM;Ramaker ME;Dorling JL;Rosen CJ;Shalaurova I;Otvos JD;Kraus VB;Kraus WE;CALERIE™ Investigators
对于许多心血管危险因素，没有进一步降低疾病风险的下限；这包括在健康成人正常范围内的数值。对于由创新技术进步确定的新出现的代谢风险因素来说，这似乎是正确的。此外，似乎有不断发展的证据表明，在正常范围内，性别和身体成分对生活方式干预的不同反应。在这项二级分析中，我们有机会在年轻（21-50岁）、体重正常的健康人群中测试这些新发现的心脏代谢风险分子生物标志物，这些人群接受了两年的卡路里限制。减少能量摄入的长期影响综合评估（CALERIE™）是一项为期24个月、多中心、随机对照试验（2007年5月至2012年11月），在健康、无肥胖的成年人中进行，以评估卡路里限制（CR）促进抗衰老适应的潜力，包括与疾病风险相关的适应。218名参与者（年龄37.9±7.2岁，体重指数（BMI） 25.1±1.7 kg/m2，平均±SD）随机分为2:1至24个月的CR（规定从基线卡路里摄入量减少25%）与随意（AL）。基线、12和24个月的空腹血浆使用核磁共振波谱技术评估脂蛋白、代谢物和炎症标志物。CR组在12个月和24个月时心血管疾病风险标志物、载脂蛋白B和GlycA、胰岛素抵抗和2型糖尿病-脂蛋白胰岛素抵抗指数和糖尿病风险指数（所有PCRvsAL≤0.0009）的平均CR为11.9%。胰岛素抵抗和糖尿病风险的改善是由于cr诱导的脂蛋白改变，特别是富含甘油三酯的脂蛋白颗粒和低密度脂蛋白颗粒的减少，向更大的高密度脂蛋白颗粒（更有效的胆固醇转运体）的转变，以及支链氨基酸（BCAAs）的减少（所有PCRvsAL≤0.004）。这些CR反应在超重的参与者中比正常体重的参与者更明显，男性比女性更明显。在没有明显危险因素或疾病的正常至轻度超重的成年人中，12个月~ 12%的CR改善了新发现的动脉粥样硬化性心血管疾病、胰岛素抵抗和2型糖尿病的危险标志物。这些标记表明，CR通过减少炎症和支链氨基酸以及将脂蛋白从致动脉粥样硬化转变为胆固醇转运来改善风险。此外，这些改善对男性和那些bmi较高的人来说更大，这表明性别和bmi的影响值得在未来关于生活方式介导的疾病风险因素改善的调查中得到关注。CALERIE™试验的设计和实施由美国国立卫生研究院（NIH）提供给四个机构、三个干预点和一个协调中心（U01 AG022132、U01 AG020478、U01 AG020487和U01 AG020480）的u拨款支持。对于这次二次分析，包括样本采集和处理，数据分析和解释，NIH向作者提供了额外的资金，如下：R01 AG054840 (MO， VBK)；R33 ag070455 (kmh, dcp, mb, sbr, ckm, lmr, skd, cfp, cjr, week)；P30 dk072476 (ckm, lmr)；U54 GM104940 （CKM， LMR）。
For many cardiovascular risk factors there is no lower limit to which further reduction will result in decreased disease risk; this includes values within ranges considered normal for healthy adults. This seems to be true for new emerging metabolic risk factors identified by innovative technological advances. Further, there seems to be ever evolving evidence of differential responses to lifestyle interventions by sex and body compositions in the normal range. In this secondary analysis, we had the opportunity to test these principles for newly identified molecular biomarkers of cardiometabolic risk in a young (21–50 years), normal weight healthy population undergoing calorie restriction for two years. The Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE™) was a 24-month, multicenter, randomized controlled trial (May 2007-November 2012) in healthy, adults without obesity to evaluate the potential for calorie restriction (CR) to promote anti-aging adaptations, including those associated with disease risk. 218 participants (age 37.9 ± 7.2 years and body mass index (BMI) 25.1 ± 1.7 kg/m2, mean±SD) were randomized 2:1 to 24 months of CR (prescribed as 25% reduction from baseline calorie intake) versus ad libitum (AL). Fasting plasma from baseline, 12, and 24 months was used for assessments of lipoproteins, metabolites, and inflammatory markers using nuclear magnetic resonance spectroscopy. Averaging 11.9% CR, the CR group had reductions at 12 and 24 months in the cardiovascular disease risk markers, apolipoprotein B and GlycA, and risks for insulin resistance and type 2 diabetes—Lipoprotein Insulin Resistance Index and Diabetes Risk Index (all PCRvsAL≤0.0009). Insulin resistance and diabetes risk improvements resulted from CR-induced alterations in lipoproteins, specifically reductions in triglyceride-rich lipoprotein particles and low-density lipoprotein particles, a shift to larger high-density lipoprotein particles (more effective cholesterol transporters), and reductions in branched chain amino acids (BCAAs) (all PCRvsAL≤0.004). These CR responses were more pronounced in overweight than normal weight participants and greater in men than women. In normal to slightly overweight adults without overt risk factors or disease, 12 months of ∼12% CR improved newly identified risk markers for atherosclerotic cardiovascular disease, insulin resistance and type 2 diabetes. These markers suggest that CR improves risks by reducing inflammation and BCAAs and shifting lipoproteins from atherogenic to cholesterol transporting. Additionally, these improvements are greater for men and for those with greater BMIs indicating sex and BMI-influences merit attention in future investigations of lifestyle-mediated improvements in disease risk factors. The CALERIE™ trial design and implementation were supported by a National Institutes of Health (NIH) U-grant provided to four institutions, the three intervention sites and a coordinating center (U01 AG022132, U01 AG020478, U01 AG020487 U01 AG020480). For this secondary analysis including sample acquisition and processing, data analysis and interpretation, additional funding was provided by the NIH to authors as follows: R01 AG054840 (MO, VBK); R33 AG070455 (KMH, DCP, MB, SBR, CKM, LMR, SKD, CFP, CJR, WEK); P30 DK072476 (CKM, LMR); and U54 GM104940 (CKM, LMR).
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DOI：
10.1152/ajpendo.00334.2019
发表时间：
2020-02-01
影响因子：
5.1
作者：
McGarrah, Robert W.;Zhang, Guo-Fang;Newgard, Christopher B.
通讯作者：
Newgard, Christopher B.
影响因子：
8.2
作者：
Glynn EL;Piner LW;Huffman KM;Slentz CA;Elliot-Penry L;AbouAssi H;White PJ;Bain JR;Muehlbauer MJ;Ilkayeva OR;Stevens RD;Porter Starr KN;Bales CW;Volpi E;Brosnan MJ;Trimmer JK;Rolph TP;Newgard CB;Kraus WE
通讯作者：
Kraus WE
影响因子：
3.6
作者：
Makri, Angeliki;Cheung, Anita;Lodish, Maya
通讯作者：
Lodish, Maya
DOI：
10.1073/pnas.0308291101
发表时间：
2004-04-27
影响因子：
11.1
作者：
Fontana, L;Meyer, TE;Holloszy, JO
通讯作者：
Holloszy, JO
影响因子：
7.7
作者：
Garvey, WT;Kwon, S;Liao, YL
通讯作者：
Liao, YL