The ob gene and insulin. A relationship leading to clues to the understanding of obesity.

Obesity and non-insulin-dependent diabetes are estimated to affect millions of people in the world. This pathology is multifactorial, comprising complex interactions of genetic and environmental factors and lacking a specific therapy. Great interest arose from the recent discovery of the ob gene expressed only in adipose tissue and coding for a protein that appears to regulate adiposity, potentially by acting as a satiety factor. We report here that in normal rats, ob mRNA is respectively up- or downregulated by a rise in insulinemia (induced by 2-day insulin infusion while maintaining euglycemia) or a decrease in insulinemia (induced by a 3-day fast). Our results also show that in genetically obese fa/fa rats studied longitudinally, white adipose tissue ob mRNA levels increase in parallel with early occurring and steadily increasing hyperinsulinemia. This results in adult obese animals having markedly higher ob mRNA levels than age-matched normoinsulinemic lean rats. Furthermore, in adult obese rats, ob mRNA escapes down-regulation as normalization of hyperinsulinemia due to fasting fails to reduce the high ob mRNA levels.