THE ROLE OF LIPOGENESIS IN THE DEVELOPMENT OF OBESITY AND DIABETES INISRAELI SAND RATS (PSAMMOMYS-OBESUS)

Obesity and diabetes in Israeli sand rats, Psammomys obesus, occur wit h the sequential transition of animals from normal insulin sensitivity to impaired insulin sensitivity, accompanied by increased adiposity, prior to insulin resistance and obesity, in a manner similar to suscep tible human populations. The current study was designed to examine the role of de novo lipid synthesis in the development of excessive weigh t gain in P. obesus. Sand rats were classified at 12 wk of age into th ree groups: A, normoglycemic normoinsulinemic; B, normoglycemic hyperi nsulinemic; C, hyperglycemic hyperinsulinemic, based on glucose and in sulin responses in fed sand rats. Body weight, liver weight, white adi pose tissue (WAT) mass and food intake were significantly elevated in Group C compared to Group A (P < 0.05). Lipogenic rate was measured by the amount of H-3 incorporated into subscapular brown adipose tissue (BAT), epidiymal WAT and liver per hour, from sand rats with and witho ut access to food. No difference in lipogenic rate was found between t he groups in BAT, indicating that this tissue is of minor importance i n whole body lipogenesis in P. obesus. In the WAT there was a greater lipogenic rate with the development of obesity and hyperinsulinemia (G roup B vs. Group A) but no difference in the liver. However, the onset of hyperglycemia (Group C) further stimulated WAT lipogenesis and ini tiated increased hepatic lipogenesis, both of which contributed to the pre-existing obesity. This study suggests that elevated lipogenesis i s not the primary cause of obesity in P. obesus, as lipogenic rate onl y markedly increases after obesity is already present in hyperglycemic animals.