Kusters Yvo Ham, Schalkwijk Casper G, Houben Alfons Jhm, Kooi M Eline, Lindeboom Lucas, Op 't Roodt Jos, Joris Peter J, Plat Jogchum, Mensink Ronald P, Barrett Eugene J, Stehouwer Coen DA
Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.
CARIM School for Cardiovascular Diseases, Maastricht, The Netherlands.
JCI Insight. 2017 Jul 6;2(13). doi: 10.1172/jci.insight.89695.
Induction of insulin resistance is a key pathway through which obesity increases risk of type 2 diabetes, hypertension, dyslipidemia, and cardiovascular events. Although the detrimental effects of obesity on insulin sensitivity are incompletely understood, accumulation of visceral, subcutaneous, and liver fat and impairment of insulin-induced muscle microvascular recruitment (MVR) may be involved. As these phenotypic changes often coincide in obesity, we aimed to unravel whether they independently contribute to insulin resistance and thus constitute separate targets for intervention.
We measured visceral (VAT) and subcutaneous adipose tissue (SAT) volumes and intrahepatic lipid (IHL) content by MRI, and whole body glucose disposal (WBGD) and MVR (using contrast-enhanced ultrasound) responses to a euglycemic insulin clamp in lean (n = 25) and abdominally obese men (n = 52). Abdominally obese men were randomized to dietary weight loss intervention or habitual diet.
Obesity-associated increases in VAT, SAT, and IHL, along with the decrease in MVR, contributed independently to insulin resistance. Moreover, a dietary weight loss intervention reduced insulin resistance, and mediation analyses showed that decreased IHL and insulin-induced MVR, but not decreased VAT or SAT volumes, independently contributed to improved insulin resistance seen with weight loss.
Quantifying the mutually independent contributions of visceral and subcutaneous adipose tissue, intrahepatic lipid, and insulin-induced muscle microvascular recruitment reveals distinct targets for treating obesity-associated insulin resistance.
Clinicaltrials.gov NCT01675401.
Funding was from the Top Institute Food and Nutrition.
胰岛素抵抗的诱导是肥胖增加2型糖尿病、高血压、血脂异常和心血管事件风险的关键途径。尽管肥胖对胰岛素敏感性的有害影响尚未完全了解，但内脏、皮下和肝脏脂肪的堆积以及胰岛素诱导的肌肉微血管募集（MVR）受损可能与之有关。由于这些表型变化在肥胖中常常同时出现，我们旨在阐明它们是否独立导致胰岛素抵抗，从而构成不同的干预靶点。
我们通过磁共振成像（MRI）测量了瘦人（n = 25）和腹型肥胖男性（n = 52）的内脏脂肪组织（VAT）和皮下脂肪组织（SAT）体积以及肝内脂质（IHL）含量，并通过对比增强超声测量了对正常血糖胰岛素钳夹的全身葡萄糖处置（WBGD）和MVR反应。腹型肥胖男性被随机分为饮食减肥干预组或常规饮食组。
与肥胖相关的VAT、SAT和IHL增加以及MVR降低独立导致胰岛素抵抗。此外，饮食减肥干预降低了胰岛素抵抗，中介分析表明，IHL降低和胰岛素诱导的MVR降低，而不是VAT或SAT体积减小，独立导致了减肥后胰岛素抵抗的改善。
量化内脏和皮下脂肪组织、肝内脂质以及胰岛素诱导的肌肉微血管募集的相互独立作用，揭示了治疗肥胖相关胰岛素抵抗的不同靶点。
Clinicaltrials.gov NCT01675401。
资助来自顶级食品与营养研究所。
