Alex Steiner

Date of Award

Fall 2019

Document Type

Open Access Thesis



First Advisor

Charles Mactutus


Obesity is one of the leading most health risks around the world, being especially problematic in the United States. A combination of high-fat diets and genetic abnormalities are to blame for the ever-growing number of obese individuals.

Melanocortin 4 receptors are vital for regulating energy expenditure and feeding behaviors; mutations of the receptors have been found to be the leading monogenetic cause of obesity. Using MC4R +/- haploinsufficient rats being fed a range of dietary fat, we investigated the physiological and motivational differences using a locomotor task, an operant task with fixed and progressive ratios, as well as a distraction operant task. Percentage of lipid deposits in the liver of each rat was also analyzed using the Area Fraction Fractionator probe for stereological measurements. MC4R +/- haploinsufficiency resulted in a phenotypic resemblance for adult-onset obesity that is worsened by poor dietary fat consumption. Results from the operant tasks indicate that motivational deficits due to MC4R +/- haploinsufficiency can be seen prior to the onset of obesity. Post-obesity motivational deficits may be dependent on dietary fat consumption. Given the full results, the MC4R circuit ties closely with the motivational dopamine circuit providing a possible target in the prevention of adult-onset obesity before developme