我们对原代人脂肪细胞的研究表明柚皮素,柑橘类黄酮,增加氧消耗率和解偶联蛋白1(UCP1)的基因表达,4型葡萄糖转运蛋白和肉碱棕榈酰转移酶1β(CPT1β)。我们调查了柚皮苷的安全性,它对代谢率的影响,以及一名女性糖尿病患者的血糖和胰岛素反应。受试者从全橙提取物中摄取150毫克柚皮素,每天3次,标准化至28%柚皮素,持续8周,并保持她通常的食物摄入量。体重,静息代谢率,呼吸商,和包括葡萄糖在内的血液化学小组,胰岛素,在基线和8周后测量安全性标记.每2周评估不良事件。我们还检查了过氧化物酶体增殖物激活受体α(PPARα)的参与,过氧化物酶体增殖物激活受体γ(PPARγ),蛋白激酶A(PKA),和蛋白激酶G(PKG)在人脂肪细胞对柚皮素治疗的反应中。与基线相比,体重减少了2.3公斤。代谢率在1小时时达到基线以上3.5%的峰值,但是呼吸商没有变化。与基线相比,胰岛素减少了18%,但血糖的变化在临床上并不显著.其他血液安全指标在其参考范围内,并且没有不良事件。PPARα和PPARγ抑制剂降低了UCP1和CPT1βmRNA的表达,但对PKA或PKG没有抑制作用。我们得出结论,柚皮素补充剂在人类中是安全的,减轻体重和胰岛素抵抗,并通过激活PPARα和PPARγ增加代谢率。柚皮素对能量消耗和胰岛素敏感性的影响值得在随机对照临床试验中进行研究。
Our studies in primary human adipocytes show that naringenin, a citrus flavonoid, increases oxygen consumption rate and gene expression of uncoupling protein 1 (UCP1), glucose transporter type 4, and carnitine palmitoyltransferase 1β (CPT1β). We investigated the safety of naringenin, its effects on metabolic rate, and blood glucose and insulin responses in a single female subject with diabetes. The subject ingested 150 mg naringenin from an extract of whole oranges standardized to 28% naringenin three times/day for 8 weeks, and maintained her usual food intake. Body weight, resting metabolic rate, respiratory quotient, and blood chemistry panel including glucose, insulin, and safety markers were measured at baseline and after 8 weeks. Adverse events were evaluated every 2 weeks. We also examined the involvement of peroxisome proliferator-activated receptor α (
PPARα), peroxisome proliferator-activated receptor γ (PPARγ), protein kinase A (PKA), and protein kinase G (PKG) in the response of human adipocytes to naringenin treatment. Compared to baseline, the body weight decreased by 2.3 kg. The metabolic rate peaked at 3.5% above baseline at 1 h, but there was no change in the respiratory quotient. Compared to baseline, insulin decreased by 18%, but the change in glucose was not clinically significant. Other blood safety markers were within their reference ranges, and there were no adverse events. UCP1 and CPT1β mRNA expression was reduced by inhibitors of
PPARα and PPARγ, but there was no effect of PKA or PKG inhibition. We conclude that naringenin supplementation is safe in humans, reduces body weight and insulin resistance, and increases metabolic rate by
PPARα and PPARγ activation. The effects of naringenin on energy expenditure and insulin sensitivity warrant investigation in a randomized controlled clinical trial.