Although some human studies suggest that obesity impairs memory and cognition, this finding is not consistent and other groups have failed to find similar associations. Because the ?apple-shaped? anatomical pattern that accompanies visceral obesity has different physiological consequences than the 'pear-shaped' distribution that reflects subcutaneous adiposity, the variable cognitive outcomes reported in obese humans may be due to the use of weight/height ratios to define obesity. Visceral obesity is accompanied by peripheral inflammation and impairs memory, while subcutaneous adiposity does not activate the innate immune system and may protect against obesity-induced cognitive dysfunction. Resident microglia in the central nervous system represent the first line of defense against inflammation, and microglial activation in impairs synaptic plasticity and cognition in other disease models. Microglia regulate neuronal plasticity via receptor-mediated signaling and physical interactions involving synaptic phagocytosis or ?stripping,? but neither of these processes has been investigated in obesity. We hypothesize that visceral and subcutaneous adiposity exert opposing effects on synaptic stripping, and that microglial interactions with neurons determine the cognitive consequences of obesity.

Public Health Relevance

The ?apple-shaped? anatomical pattern that accompanies visceral adiposity increases risk for multiple chronic diseases, including conditions that impact the brain. Although visceral obesity has been linked with deficits in memory and cognition, all fat is not bad, because the 'pear-shaped' distribution that reflects subcutaneous adiposity does not predict cognitive impairment and may be protective. The opposing neural consequences of visceral and subcutaneous adiposity are mirrored by differences in peripheral inflammation, but the role of the immune system in communication between fat and brain remains poorly understood. These experiments examine how body fat distribution recruits the immune system to regulate memory, with the goal of understanding risk factors for cognitive impairment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK110586-01A1
Application #
9311908
Study Section
Neuroendocrinology, Neuroimmunology, Rhythms and Sleep Study Section (NNRS)
Program Officer
Stoeckel, Luke
Project Start
2017-07-01
Project End
2022-05-31
Budget Start
2017-07-01
Budget End
2018-05-31
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Augusta University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
City
Augusta
State
GA
Country
United States
Zip Code
30912