The goal of this project is to develop a minimally invasive treatment for metabolic syndrome associated with obesity. Metabolic syndrome includes diabetogenic, atherogenic, pro-thrombotic and pro-inflammatory metabolic abnormalities; which often present during childhood. Patients with obesity-induced metabolic syndrome have a high risk of cardiovascular disease and type 2 diabetes. The most prevalent form of obesity-associated metabolic syndrome is related to the accumulation of visceral fat, rather than subcutaneous fat or total body fat. Visceral fat and its resident macrophages produce pro-inflammatory cytokines (e.g., necrosis factor-alpha, leptin, and interleukin-6) that are implicated in chronic low-grade inflammation which subsequently lead to metabolic syndrome in the obese. Recent animal studies show that loss of visceral fat may generate substantial improvements in the metabolic risk factor profile. This notion has important clinical implications as it recognize visceral adiposity as a therapeutic target for the management of metabolic syndrome in high-risk patients. While lifestyle modifications in the form of caloric restriction, pharmacotherapy and bariatric surgery have all been shown to provide improvement in metabolic risk factors associated with obesity, it is not known if these improvements are maintained over time. Improvement also takes time, (i.e., several months to years) to show beneficial effects. More importantly none of the existing interventions specifically target visceral fat which is thought to play a causative role in the metabolic syndrome. Thus, in this application we will investigate de-bulking of visceral fat by thermal ablation as a treatment option for obesity-induced metabolic syndrome. We hypothesize that HIFU treatment of visceral fat can improve insulin action in obese rats and provide a non-surgical alternative to visceral fat resection. To test this hypothesis, we will design, build, and validate an MR-guided focused ultrasound system for the ablation of visceral fat in a rodent model of metabolic syndrome.
An epigenetic map of age-associated autosomal loci in northern European families at high risk for the metabolic syndrome
