Kadowaki Satoshi, Tamura Yoshifumi, Sugimoto Daisuke, Kaga Hideyoshi, Suzuki Ruriko, Someya Yuki, Yamasaki Nozomu, Sato Motonori, Kakehi Saori, Kanazawa Akio, Kawamori Ryuzo, Watada Hirotaka
Department of Metabolism & Endocrinology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Sportology Center, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
J Clin Med. 2023 Jun 16;12(12):4084. doi: 10.3390/jcm12124084.
A short-term high-calorie high-fat diet (HCHFD) impairs insulin sensitivity in non-obese South Asian but not Caucasian men; however, the effect of short-term HCHFD on insulin sensitivity in East Asians is unknown. We recruited 21 healthy non-obese Japanese men to evaluate metabolic parameters and gut microbiota before and after 6-day HCHFD consisting of a regular diet plus a 45% energy excess with dairy fat supplementation. We evaluated tissue-specific insulin sensitivity and metabolic clearance rate of insulin (MCRI) using a two-step hyperinsulinemic euglycemic clamp, glucose tolerance using the glucose tolerance test, and measured ectopic fat in muscle and the liver using ¹H-magnetic resonance spectroscopy. The primary outcome of this study was insulin sensitivity measured by the clamp study. The secondary/exploratory outcomes were other metabolic changes. After HCHFD, levels of circulating lipopolysaccharide binding protein (LBP), a marker of endotoxemia, increased by 14%. In addition, intramyocellular lipid levels in the tibialis anterior and soleus and intrahepatic lipid levels increased by 47%, 31%, and 200%, respectively. Insulin sensitivity decreased by 4% in muscle and 8% in liver. However, even with reduced insulin sensitivity, glucose metabolism was maintained by increased serum insulin concentrations due to lower MCRI and higher endogenous insulin secretion during the clamp. Glucose levels during the meal tolerance test were comparable before and after HCHFD. In conclusion, short-term HCHFD impaired insulin sensitivity in the muscle and livers of non-obese Japanese men with increased LBP and ectopic fat accumulation. Elevated insulin levels from modulated insulin secretion and clearance might contribute to the maintenance of normal glucose metabolism during the clamp and meal tolerance test.
短期高热量高脂肪饮食（HCHFD）会损害非肥胖南亚男性的胰岛素敏感性，但对白种男性无此影响；然而，短期HCHFD对东亚人胰岛素敏感性的影响尚不清楚。我们招募了21名健康的非肥胖日本男性，以评估在为期6天的HCHFD（由常规饮食加45%的能量过剩及补充乳脂肪组成）前后的代谢参数和肠道微生物群。我们使用两步高胰岛素正葡萄糖钳夹技术评估组织特异性胰岛素敏感性和胰岛素的代谢清除率（MCRI），通过葡萄糖耐量试验评估葡萄糖耐量，并使用¹H-磁共振波谱测量肌肉和肝脏中的异位脂肪。本研究的主要结局是通过钳夹研究测量的胰岛素敏感性。次要/探索性结局是其他代谢变化。HCHFD后，内毒素血症标志物循环脂多糖结合蛋白（LBP）水平升高了14%。此外，胫前肌和比目鱼肌的肌内脂质水平以及肝内脂质水平分别升高了47%、31%和200%。肌肉中的胰岛素敏感性降低了4%，肝脏中降低了8%。然而，即使胰岛素敏感性降低，由于钳夹期间MCRI降低和内源性胰岛素分泌增加，血清胰岛素浓度升高维持了葡萄糖代谢。HCHFD前后餐耐量试验期间的血糖水平相当。总之，短期HCHFD损害了非肥胖日本男性肌肉和肝脏的胰岛素敏感性，同时LBP升高和异位脂肪堆积增加。胰岛素分泌和清除调节导致的胰岛素水平升高可能有助于在钳夹和餐耐量试验期间维持正常的葡萄糖代谢。
