FREE FATTY ACIDS (FFA), A LINK BETWEEN OBESITY AND INSULIN RESISTANCE

Guenther Boden, M.D.

Division of Endocrinology/Diabetes/Metabolism and the General Clinical Research Center, Temple University School of Medicine, Philadelphia, PA

Received 1/21/98 Accepted 1/31/98

2. INTRODUCTION

Obesity is associated with insulin resistance and hyperinsulinemia, two important cardiovascular risk factors (1,2). The fact that hyperinsulinemia and insulin resistance increase with weight gain and decrease with weight loss (3-6) suggests that this is a cause and effect relationship. What remains uncertain is how obesity produces insulin resistance and hyperinsulinemia. It has recently become clear, however, that FFA play a pivotal role in this process. Plasma levels of FFA are elevated in obesity (7,8) primarily because a greater than normal amount of FFA is released from the expanded adipose tissue mass even though the rate of lipolysis from individual fat cells appears to be normal (9,10). The following is a review of the evidence, gained from studies in human subjects, which shows that elevations of plasma FFA produce peripheral and probably also hepatic insulin resistance in healthy subjects and in patients with Type II diabetes.