Vascular Inflammation, Insulin Resistance, and Reduced Nitric Oxide Production Precede the Onset of Peripheral Insulin Resistance

• DOI: 10.1161/atvbaha.108.169722
• Publication Date: 2008-09-05T01:57:25Z
• Authors: Francis Kim; Matilda Pham; Ezekiel Maloney; Norma O. Rizzo; Gregory J. Morton; Brent E. Wisse; Elizabeth A. Kirk; Alan Chait; Michael W. Schwartz
• Keywords: Inflammation; Male; 2. Zero hunger; 0303 health sciences; Body Weight; Nitric Oxide; Dietary Fats; I-kappa B Kinase; Mice, Inbred C57BL; Disease Models, Animal; Mice; 03 medical and health sciences; Glucose; Adipose Tissue; Liver; Disease Progression; Animals; Insulin; Endothelium, Vascular; Inflammation Mediators; Insulin Resistance; Muscle, Skeletal; Adiposity

Obesity causes inflammation and insulin resistance in the vasculature as well tissues involved glucose metabolism such liver, muscle, adipose tissue. To investigate relative susceptibility of vascular tissue to these effects, we determined time course over which develops various mice with diet-induced obesity (DIO) compared tissue-based responses changes circulating inflammatory markers.Adult male C57BL/6 were fed either a control low-fat diet (LF; 10% saturated fat) or high-fat (HF, 60% for durations ranging between 1 14 weeks. Cellular assessed by measuring phospho-IkappaBalpha insulin-induced phosphorylation Akt, respectively, extracts thoracic aorta, skeletal visceral fat. As expected, HF feeding induced rapid increases body weight, fat mass, fasting levels controls, each achieved statistical significance within 4 Whereas plasma markers became elevated relatively late DIO (eg, serum amyloid A [SAA], Week 14), aortic lysates 2-fold first week. The early onset was accompanied biochemical evidence both endothelial dysfunction (reduced nitric oxide production; induction intracellular adhesion molecule-1 cell molecule-1) (impaired Akt eNOS). Although also detected muscle liver HF-fed animals, observed much later (between 8 weeks feeding), they not until weeks.During feeding, develop before are This observation suggests that is more susceptible than other deleterious effects nutrient overload.