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Theses Doctoral

Diet Palatability and Body Weight Regulation

Gallop, Molly Rachel

Body weight in mammals is defended so that small changes in weight evoke neuroendocrine and metabolic responses that encourage a return to one’s previous weight. While these homeostatic responses have been more commonly studied in the case of weight loss, our lab has developed a mouse model of overfeeding to study the physiology of defense against weight gain. In response to overfeeding-induced weight gain, the return to previous body weight is mediated primarily by a striking reduction in food intake, which persists until pre-overfeeding body weight is restored. However, preliminary data do not suggest activation of anorectic POMC neurons which reduce food intake or inhibition of the appetite stimulating AgRP or NPY neurons in the arcuate nucleus of the hypothalamus. Furthermore, we found that adipose tissue from overfed mice does not show the same inflammatory response as mice that have become obese slowly due to ad libitum high-fat diet (HFD) consumption.

Paradoxically, despite the existence of mammalian systems that defend against weight gain, average body weight in humans has been on the rise over the last half century. Concomitant with the rise in obesity rates, has been increasing availability and consumption of processed and fast foods which are generally high in sugar, salt, and fat making them extremely palatable and calorically dense. Both the caloric density and enticing taste of the foods have been implicated in causing overconsumption and contributing to a rise in average body weight and prevalence of obesity. Thus, while controlling for caloric density we have investigated whether diet palatability can increase body weight and suppress defense against weight gain in mice.

We designed our studies so that all diets were of the same caloric density and therefore varied only proportion of calories derived from fats, carbohydrates, and protein. Palatability is the relative subjective preference of one food over another; in our mouse studies we equated preference, when given, a choice with palatability. We confirmed that liquid diets sweetened with sucrose or the non-nutritive sweeteners sucralose and saccharin were preferred over non-sweetened diets. In 12 day feeding studies, although we found that sweetened diets were more palatable than unsweetened diets, they did not increase caloric intake or body weight. Next, we tested whether increasing percent calories from fat leads to increases in palatability or caloric intake. In a similar 12 day feeding preference study, we found diets higher in percent calories from fat (high-fat diet = HFD) were preferred to diets with lower percent calories from fat (low-fat diet = LFD) and that the access to a HFD increased caloric intake and body weight. Employing a four-week single diet feeding study, we also found a linear relationship between percent calories from fat and caloric intake consistent with our hypothesis that percent calories from fat is sensed and modulates caloric intake.

To test whether HFD can suppress defense of body weight, we used an overfeeding paradigm which I help develop, to test whether ad libitum access to a HFD prevented a return to the original body weight following overfeeding. HFD did attenuate the hypophagic response to overfeeding and prevented a return to each mouse’s initial weight with the mice having access to the HFD mice stabilizing at a higher body weight. Palatability has traditionally been ascribed to sensing of smell and taste, however, macronutrients can also be sensed within intestinal tract. To determine whether the effects of percent calories from fat require naso-oral sensing to modulate feeding behavior, we used an intragastric feeding system to bypass taste and smell and deliver HFD directly into the stomach of mice. Even in the absence of oropharyngeal sensing, HFD in the gut was sufficient to increase ad libitum caloric intake of a low-fat diet and increase body weight. Finally, based on our findings of post-oral fat sensing driving caloric intake, we tested whether post-oral sensing of percent calories from fat was sufficient to condition a flavor preference. However, we found that when caloric density was controlled, a high percent calories from fat was not sufficient to condition a flavor preference.

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More About This Work

Academic Units
Nutritional and Metabolic Biology
Thesis Advisors
Ferrante, Anthony W.
Degree
Ph.D., Columbia University
Published Here
August 18, 2021