Histidine supplementation improves insulin resistance through suppressed inflammation in obese women with the metabolic syndrome: a randomised controlled trial
Histidine supplementation improves insulin resistance through suppressed inflammation in obese women with the metabolic syndrome: a randomised controlled trial
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组氨酸补充剂通过抑制患有代谢综合征的肥胖女性的炎症来改善胰岛素抵抗：一项随机对照试验
DOI：
10.1007/s00125-013-2839-7
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发表时间：
2013-05-01
期刊：
影响因子：
8.2
通讯作者：
Li, Y.
中科院分区：
文献类型：
--
作者：
Feng, R. N.;Niu, Y. C.;Li, Y.
目的/假设增加炎症和氧化应激与胰岛素抵抗（IR）和代谢性疾病有关。血清组氨酸水平较低，与肥胖女性的炎症和氧化应激负相关。这项研究的目的是评估肥胖女性中补充组氨酸，炎症，氧化应激和代谢性疾病的疗效。患有代谢综合征（METS）的肥胖女性（METS）总共100名肥胖女性，年龄为33-51岁的BMI> = 28 kg/m（2）的肥胖女性（2）和诊断为NOISTER a DOWN-METS STINE SHINDORN STINE CONDENCE CORMINDY在健康检查中，并在健康状态下进行了诊断，并在健康状态下进行了诊断。安慰剂对照试验。研究人员使用依次编号的密封信封将参与者分配给干预措施，并接受4 g/天组氨酸（n = 50）或相同的安慰剂（n = 50），持续12周。然后，参与者每2周就会参加同一诊所进行预定的访谈，并计算返回的平板电脑。在基线和12周时测量了血清组氨酸，HOMA-IR，BMI，腰围，脂肪质量，血清NEFA和与炎症和氧化应激相关的变量。参与者，检查评估结果的医师和研究人员对小组分配视而不见。此外，在脂肪细胞中还探索了组氨酸的炎症机制。在12周时，总共有92名参与者完成了这条路线。与安慰剂组（n = 47）相比，补充组氨酸显着降低了HOMA -IR（-1.09 [95％CI -1.49，-0.68]），BMI（-0.86 kg/m（2）[95％CI -1.55，-0.17]，-0.17]，-0.17]，-0.17]，腰围（-2.86 CM） -1.86]），脂肪质量（-2.71 kg [95％CI -3.69，-1.73]），血清NEFA（-173.26 Mu Mol/L [95％CI -208.57，-137.94]），血清炎症细胞因子（TNF -Alpha，-3.96 pg） -2.62]; IL -6，-2.15 pg/ml [95％CI -2.52，-1.78]），氧化压力（超氧化物歧化酶，17.84 u/ml [95％CI 15.03，20.65;组氨酸和脂联素通过18.23 Mu mol/L [95％CI 11.74，24.71]和2.02 ng/ml [95％CI 0.60，3.44]分别在组氨酸补充组中（n = 45）。血清组氨酸的变化与IR的变化及其风险因素之间存在显着相关性。干预期间未观察到副作用。 In vitro study indicated that histidine suppresses IL6 and TNF mRNA expression and nuclear factor kappa-B (NF-kappa B) protein production in palmitic acid-induced adipocytes in a dose-dependent manner, and these changes were diminished by an inhibitor of NF-kappa B.Conclusions/interpretation Histidine supplementation could improve IR, reduce BMI, fat mass and NEFA and suppress肥胖妇女的炎症和氧化应激；组氨酸可以通过抑制脂肪细胞中NF-kappa B途径抑制的炎性细胞因子表达来改善IR。
Aims/hypothesisIncreased inflammation and oxidative stress are associated with insulin resistance (IR) and metabolic disorders. Serum histidine levels are lower and are negatively associated with inflammation and oxidative stress in obese women. The objective of this study was to evaluate the efficacy of histidine supplementation on IR, inflammation, oxidative stress and metabolic disorders in obese women with the metabolic syndrome (MetS).MethodsA total of 100 obese women aged 33–51 years with BMI ≥ 28 kg/m2and diagnosed with MetS were included following a health examination in the community hospital in this randomised, double-blinded, placebo-controlled trial. Participants were allocated to interventions by an investigator using sequentially numbered sealed envelopes and received 4 g/day histidine (n= 50) or identical placebo (n= 50) for 12 weeks. Participants then attended the same clinic every 2 weeks for scheduled interviews and to count tablets returned. Serum histidine, HOMA-IR, BMI, waist circumference, fat mass, serum NEFA, and variables connected to inflammation and oxidative stress were measured at baseline and 12 weeks. Participants, examining physicians and investigators assessing the outcomes were blinded to group assignment. In addition, the inflammatory mechanisms of histidine were also explored in adipocytes.ResultsAt 12 weeks, a total of 92 participants completed this trail. Compared with the placebo group (n= 47), histidine supplementation significantly decreased HOMA-IR (−1.09 [95% CI −1.49, −0.68]), BMI (−0.86 kg/m2[95% CI −1.55, −0.17]), waist circumference (−2.86 cm [95% CI −3.86, −1.86]), fat mass (−2.71 kg [95% CI −3.69, −1.73]), serum NEFA (−173.26 μmol/l [95% CI −208.57, −137.94]), serum inflammatory cytokines (TNF-α, −3.96 pg/ml [95% CI −5.29, −2.62]; IL-6, −2.15 pg/ml [95% CI −2.52, −1.78]), oxidative stress (superoxide dismutase, 17.84 U/ml [95% CI 15.03, 20.65]; glutathione peroxidase, 13.71 nmol/ml [95% CI 9.65, 17.78]) and increased serum histidine and adiponectin by 18.23 μmol/l [95% CI 11.74, 24.71] and 2.02 ng/ml [95% CI 0.60, 3.44] in histidine supplementation group (n= 45), respectively. There were significant correlations between changes in serum histidine and changes of IR and its risk factors. No side effects were observed during the intervention. In vitro study indicated that histidine suppressesIL6andTNFmRNA expression and nuclear factor kappa-B (NF-κB) protein production in palmitic acid-induced adipocytes in a dose-dependent manner, and these changes were diminished by an inhibitor of NF-κB.Conclusions/interpretationHistidine supplementation could improve IR, reduce BMI, fat mass and NEFA and suppress inflammation and oxidative stress in obese women with MetS; histidine could improve IR through suppressed pro-inflammatory cytokine expression, possibly by the NF-κB pathway, in adipocytes.Trial registrationwww.chictr.org/cn/ChiCTR-TRC-11001551FundingThe study was supported by the National Natural Science Fund of China (No. 81202184, 81130049, 81102112), Heilongjiang Post/doctoral Fund (No. LBN-Z12193) and Key Laboratory of Nutrition and Food Hygiene (Harbin Medical University, Heilongjiang Higher Education Institutions, No. YYKFKT1202).