Hyperlipidemic diet causes loss of olfactory sensory neurons, reduces olfactory discrimination, and disrupts odor-reversal learning.
Currently, 65% of Americans are overweight, which leads to well-supported cardiovascular and cognitive declines. Little, however, is known concerning obesity's impact on sensory systems. Because olfaction is linked with ingestive behavior to guide food choice, its potential dysfunction during obesity could evoke a positive feedback loop to perpetuate poor ingestive behaviors. To determine the effect of chronic energy imbalance and reveal any structural or functional changes associated with obesity, we induced long-term, diet-induced obesity by challenging mice to high-fat diets: (1) in an obesity-prone (C57BL/6J) and obesity-resistant (Kv1.3(-/-)) line of mice, and compared this with (2) late-onset, genetic-induced obesity in MC4R(-/-) mice in which diabetes secondarily precipitates after disruption of the hypothalamic axis. We report marked loss of olfactory sensory neurons and their axonal projections after exposure to a fatty diet, with a concomitant reduction in electro-olfactogram amplitude. Loss of olfactory neurons and associated circuitry is linked to changes in neuronal proliferation and normal apoptotic cycles. Using a computer-controlled, liquid-based olfactometer, mice maintained on fatty diets learn reward-reinforced behaviors more slowly, have deficits in reversal learning demonstrating behavioral inflexibility, and exhibit reduced olfactory discrimination. When obese mice are removed from their high-fat diet to regain normal body weight and fasting glucose, olfactory dysfunctions are retained. We conclude that chronic energy imbalance therefore presents long-lasting structural and functional changes in the operation of the sensory system designed to encode external and internal chemical information and leads to altered olfactory- and reward-driven behaviors.
Department of Biological Science and Program in Neuroscience, Florida State University, Tallahassee, Florida 32306.
Nicolas
N
Thiebaud
Department of Biology, University of West Georgia, Carrollton, Georgia 30118.
Melissa C
MC
Johnson
Department of Biological Science and Program in Neuroscience, Florida State University, Tallahassee, Florida 32306.
Jessica L
JL
Butler
Department of Biological Science and Program in Neuroscience, Florida State University, Tallahassee, Florida 32306.
Genevieve A
GA
Bell
Department of Biological Science and Program in Neuroscience, Florida State University, Tallahassee, Florida 32306.
Kassandra L
KL
Ferguson
Department of Biological Science and Program in Neuroscience, Florida State University, Tallahassee, Florida 32306.
Andrew R
AR
Fadool
Department of Mechanical Engineering, Florida State University, Tallahassee, Florida 32310.
James C
JC
Fadool
Larry A. Ryle High School, Union, Kentucky 41091, and.
Alana M
AM
Gale
Larry A. Ryle High School, Union, Kentucky 41091, and.
David S
DS
Gale
Department of Biological Science and Program in Neuroscience, Florida State University, Tallahassee, Florida 32306, Institute of Molecular Biophysics, Florida State University, Tallahassee, Florida 32306 dfadool@bio.fsu.edu.
Debra A
DA
Fadool
D000818:Animals; D001786:Blood Glucose; D059305:Diet, High-Fat / Q000009:adverse effects*; D004193:Discrimination Learning / Q000502:physiology*; D008297:Male; D051379:Mice; D009765:Obesity / Q000209:etiology / Q000503:physiopathology; D009812:Odorants; D055696:Olfactory Perception / Q000502:physiology*; D012193:Reversal Learning / Q000502:physiology*; D011984:Sensory Receptor Cells / Q000502:physiology*; D012903:Smell / Q000502:physiology*
D001786:Blood Glucose
chemical senses; circuitry; metabolism; obesity; olfactory; sensory