Obesity, hypertension, and insulin resistance.

Abstract

This article summarizes material presented at the meeting of the American Society of Hypertension (ASH) in New York, New York, May, 2002, as well as presentations at the American Diabetes Association (ADA) Annual Meeting in San Francisco, California, June, 2002. At a symposium addressing the relationships between obesity, hypertension, and cardiovascular disease at the ASH, Roger Unger (Dallas, TX) discussed lipotoxicity and the metabolic syndrome. He pointed out that over that past 50 years there has been a great change in the food environment, so that the “mechanism for preloading calories, storing them for when a famine occurred,” has led to “hypertrophy and hyperplasia of those adipocytes […]. Famines were eliminated and replaced by a never-ending stream of high-quantity, high-fat, high-carbohydrate foods at the same time that physical exertion dropped to an all-time low.” This has led to a progressive increase in obesity, particularly over the past two decades. “As long as the excess fat remains in the adipocyte,” he stated, “health is not deleteriously affected,” but an “increase in ectopic deposition of lipids” causes the insulin-resistant state, with insulin resistance per se characterized by Unger as “not the proximal cause of the syndrome.” Unger examined monogenic disorders of lack of leptin action to understand “the mechanism of the disorder.” These syndromes, which lead to components of the metabolic syndrome, suggest that leptin resistance or deficiency may be a more central cause than insulin resistance. The normal actions of leptin can be seen in animal models of obesity, with overfeeding leading to hyperleptinemia, which may cause fat to deposit primarily in the adipocyte. Normal islets, as an example, “fill up with triglycerides” when incubated with fatty acids, but this can be prevented by administration of leptin. When leptin action is insufficient, as seen in the fatty/fatty ( fa/fa ) rat with loss-of-function …