Adipose and Fatty Liver in the Metabolic Syndrome

University Of California San Diego, La Jolla CA

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Abstract

DESCRIPTION (provided by applicant): In the final 3 decades of the 20th Century the prevalence of childhood obesity tripled in the United States. Not only are more children obese, but the severity of obesity has increased as well. Thus those children who are overweight exceed the healthy range by a larger amount. The consequence of this public health crisis is that more and more children are experiencing weight-related health complications. The metabolic syndrome is a clustering of adverse health conditions that predisposes an individual to the development of cardiovascular disease and type 2 diabetes mellitus. In childhood the metabolic syndrome is seen almost exclusively in obese children. The major components of the metabolic syndrome are abnormalities in glucose and fat metabolism as well as blood pressure. A major unanswered question is, why do some obese children manifest some or all of the complications of the metabolic syndrome while others develop none? The adverse effects of excess body weight are due to the amount of fat and where the fat is located. Fat deep inside the abdomen, termed visceral fat, is believed to cause greater harm than fat located outside the abdomen. One way in which visceral fat may mediate its effects is by overwhelming the liver with fat. In children, fatty liver is only recently received much attention as an important problem. Those children with fatty liver often have many of the same abnormalities as are present in the metabolic syndrome. We hypothesize that the amount of fat inside the abdomen is strongly related to the amount of fat within the liver. Furthermore, we hypothesize that liver fat is both a marker of the metabolic syndrome as well as a direct contributor to the development of the metabolic syndrome. We also believe that race and ethnicity modify the relationships between abdominal fat, liver fat, and the metabolic syndrome. Therefore we propose to measure all of the fat within the body and determine its specific locations using sophisticated imaging techniques some of which have not been previously applied to children. We will also measure the components of the metabolic syndrome. These studies will include a racially and ethnically diverse group of overweight children. The current exploratory proposal will develop data and techniques than can be applied to long-term studies targeted at defining optimal treatments for obese children with the metabolic syndrome of both genders and all races and ethnicities.