The burgeoning prevalence of dietary linked obesity and overweight conditions from the age of adolescence and adulthood has reached epidemic proportions in industrialized nations globally since the adoption of low fat-high carbohydrate diets in an attempt to address issues of coronary heart disease. The development of dietary-linked insulin resistance (IR) is one of the most common observations in obesity and overweight conditions and is associated with systemic hypoxia in adipose tissue and a chronic systemic inflammatory state.The IR affects multiple elements of energy metabolism and oxidative free radical generation in both somatic and neural tissues and in addition to cytokine-linked chronic inflammation that likely originates in adipose tissue depots.The LA/Ntul//-cp rat is a congenic animal model of obesity that develops chronic IR but not diabetes (NIDDM) or hypertension and a 25% reduction in typical lifespan in the obese phenotype. The effects of chronic 54% (w/w) starch (ST)- or sucrose (SUC)-based nutritionally complete diets onobesity and brain composition were determined in aging congenic obese rats demonstrating IR but not NIDDM or other common comorbidities in lean and obese littermates at 10.5 months of age.Body weights and adiposity of obese ratswere 2.5 to 3-fold greater than lean rats and were greater when fed the SUC than the ST diet.Plasma Insulin and IR were 4.3-fold greater in obese than lean and were further increased in obese-SUC fed rats, but both phenotypes remained  euglycemic on both diets. Brain mass was decreased by 25% in ST-fed obese animals, with proportional decreases in brain protein and DNA content. Brain mass, protein and DNA content were further decreased in both lean and obese phenotypes when fed SUC vs ST diets. These results are consistent with obesity and insulin resistance as risk factors contributing to the development of brain shrinkage and senescencein an aging rat model and provide insight into the mechanisms contributing to brain senescence and cognitive decline in aging.
Keywords: Obesity, Brain composition, Hyperinsulinemia, Neuroinflammation, Neurosenescence, DNA, Cognitive Decline, Carbohydrate, Rat