Uncontrolled adipocyte proliferation is not the primary lesion in the genetically-obese Zucker rat.

One of several hypotheses concerning the nature of the genetic lesion which produces obesity in the Zucker fatty rat is that a defect in control of cellular proliferation in adipose tissue leads to hypercellular-hypertrophic obesity with all its metabolic and behavioral sequalae. Three lines of evidence are presented which render this hypothesis untenable: (1) maximal cell enlargement precedes maximum rate of cell addition in adipose tissue; (2) lipectomized obese rats do not regenerate subcutaneous adipocytes; and (3) cultured adipocyte precursors from obese rat adipose tissue grow at the same rate as do cells cultured from lean tissue. An alternative hypothesis that an alteration in hepatic lipid metabolism may be the locus of the genetic lesion is presented along with evidence from in-vivo and in-vitro studies of hepatic lipogenesis in the Zucker rat.