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Endocrinology. 2017 May 1;158(5):1152-1159. doi: 10.1210/en.2016-1475.

Assisted Reproductive Technologies Predispose to Insulin Resistance and Obesity in Male Mice Challenged With a High-Fat Diet.

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Departments of Cardiology.
Clinical Research, University Hospital Bern, 3010 Bern, Switzerland.
Department of Internal Medicine, University Hospital, 1011 Lausanne, Switzerland.
Facultad de Ciencias, Departamento de Biología, Universidad de Tarapacá, 1775 Arica, Chile.


Assisted reproductive technology (ART) alters glucose homeostasis in mice and humans, but the underlying mechanisms are incompletely understood. ART induces endothelial dysfunction and arterial hypertension by epigenetic alteration of the endothelial nitric oxide synthase (eNOS) gene. In eNOS-deficient mice, insulin resistance is related to impaired insulin stimulation of muscle blood flow and substrate delivery and defective intrinsic skeletal muscle glucose uptake. We therefore assessed glucose tolerance, insulin sensitivity (euglycemic clamp), insulin stimulation of muscle blood flow in vivo, and muscle glucose uptake in vitro in male ART and control mice fed a normal chow (NC) or challenged with a high-fat diet (HFD) during 8 weeks. Glucose tolerance and insulin sensitivity were similar in NC-fed animals. When challenged with a HFD, however, ART mice developed exaggerated obesity, fasting hyperinsulinemia and hyperglycemia, and a 20% lower insulin-stimulated glucose utilization than did control mice (steady-state glucose infusion rate (GIR), 51.3 ± 7.3 vs 64.0 ± 10.8 mg/kg/min, P = 0.012). ART-induced insulin resistance was associated with defective insulin stimulation of muscle blood flow, whereas intrinsic skeletal muscle glucose uptake was normal. In conclusion, ART-induced endothelial dysfunction, when challenged with a metabolic stress, facilitates glucose intolerance and insulin resistance. Similar mechanisms may contribute to ART-induced alterations of the metabolic phenotype in humans.

[Indexed for MEDLINE]

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