Effect of the obese phenotype on brain composition in congenic lean and obese LA/Ntul//-cp rats

Abstract

To determine if the obese phenotype impacted on brain development and composition, groups of congenic male lean and obese littermates of the LA/Ntul//-cp rat strain were fed on a standardized nutritionally adequate diet in littermate pairs from weaning until adulthood. The obese phenotype of his strain develops early onset chronic hyperinsulinemia associated with hypertrophic-hyperplastic obesity during early postweaning growth. At 10.5 months of age, animals were sacrificed by cervical dislocation, and brain tissues excised in its entirety, weighed to the nearest mg, and measures of protein, DNA and lipid determined. Body weights (BW) of obese were significantly greater than lean. Brain mass (BrM) of lean > obese, and BrM:BW of lean was greater obese. Brain protein content (BPC) and Brain DNA (BDNA) of lean was greater than obese. Brain lipid as a percent was similar in both phenotypes and net brain lipid content was proportional to brain mass. Total body fat mass of obese was significantly greater than occurred in lean littermates. Inflammatory cytokines residing in adipose tissue have been reported to contribute to DNA damage in neuronal and other tissues, impede cell replication, and accelerate cell senescence. These results indicate that brain growth and cellular development is impaired in the hyperinsulinemia-prone obese phenotype of this strain, and are likely associated with development of a chronic inflammatory syndrome and cytokine expression common to excessive fat accretion and obesity