Haufe S, Engeli S, Kaminski J, Witt H, Rein D, Kamlage B, Utz W, Fuhrmann J C, Haas V, Mähler A, Schulz-Menger J, Luft F C, Boschmann M, Jordan J
Institute for Clinical Pharmacology, Hannover Medical School, Hannover, Germany.
Franz Volhard Clinical Research Center at the Experimental and Clinical Research Center, Charité University Medical School and Max Delbrück Center for Molecular Medicine, Berlin, Germany.
Nutr Metab Cardiovasc Dis. 2017 Oct;27(10):858-864. doi: 10.1016/j.numecd.2017.07.001. Epub 2017 Jul 11.
BACKGROUND & AIMS: 3-Hydroxyisobutyrate (3-HIB), a catabolic intermediate of the BCAA valine, which stimulates muscle fatty acid uptake, has been implicated in the pathogenesis of insulin resistance. We tested the hypothesis that circulating 3-HIB herald insulin resistance and that metabolic improvement with weight loss are related to changes in BCAAs and 3-HIB.
We analyzed plasma and urine in 109 overweight to obese individuals before and after six months on hypocaloric diets reduced in either carbohydrates or fat. We calculated the homeostasis model assessment index (HOMA-IR) and whole body insulin sensitivity from oral glucose tolerance tests and measured intramyocellular fat by magnetic resonance spectroscopy. BCAAs and 3-HIB plasma concentrations were inversely related to insulin sensitivity but not to intramyocellular fat content at baseline. With 7.4 ± 4.5% weight loss mean BCAA and 3-HIB plasma concentrations did not change, irrespective of dietary macronutrient content. Individual changes in 3-HIB with 6-month diet but not BCAAs were correlated to the change in whole body insulin sensitivity and HOMA-IR independently of BMI changes.
3-HIB relates to insulin sensitivity but is not associated with intramyocellular fat content in overweight to obese individuals. Moreover, changes in 3-HIB rather than changes in BCAAs are associated with metabolic improvements with weight loss. Registration number for clinical trials: ClinicalTrials.gov Identifier: NCT00956566.
3-羟基异丁酸（3-HIB）是支链氨基酸缬氨酸的一种分解代谢中间产物，可刺激肌肉脂肪酸摄取，与胰岛素抵抗的发病机制有关。我们检验了以下假设：循环中的3-HIB预示胰岛素抵抗，体重减轻带来的代谢改善与支链氨基酸和3-HIB的变化有关。
我们分析了109名超重至肥胖个体在接受低热量饮食（碳水化合物或脂肪含量减少）6个月前后的血浆和尿液。我们通过口服葡萄糖耐量试验计算稳态模型评估指数（HOMA-IR）和全身胰岛素敏感性，并通过磁共振波谱测量肌细胞内脂肪。在基线时，支链氨基酸和3-HIB的血浆浓度与胰岛素敏感性呈负相关，但与肌细胞内脂肪含量无关。体重平均减轻7.4±4.5%时，支链氨基酸和3-HIB的血浆浓度未发生变化，与饮食中常量营养素的含量无关。6个月饮食后3-HIB的个体变化而非支链氨基酸的变化与全身胰岛素敏感性和HOMA-IR的变化相关，且独立于体重指数的变化。
在超重至肥胖个体中，3-HIB与胰岛素敏感性相关，但与肌细胞内脂肪含量无关。此外，与支链氨基酸的变化相比，3-HIB的变化与体重减轻带来的代谢改善有关。临床试验注册号：ClinicalTrials.gov标识符：NCT00956566。
