Background and ObjectiveAnimal studies can be a great tool to investigate sex differences in a variety of different ways, including behavioral and physiological responses to drug treatments and different “lifestyle variables” such as diets. Consumption of both high‐fat diets and alcohol is known to affect anxiety behaviors and overall health. This project investigated how high‐fat diet and alcohol access and its combination affected the behavior and physiology of male and female C57BL/6J mice.MethodMice were separated into three food groups: high‐fat diet, 10% fat diet, and regular chow, and each group was paired with either water or 10% alcohol. Behavioral assays included diet and alcohol preference, light‐dark box, open field, and feeding and drinking measurements. Physiological measures included glucose tolerance tests and measurement of brain‐derived neurotrophic factor, insulin, and leptin levels.ResultsFemales and males differed in the open field, as male mice decreased activity, while females increased activity when consuming high‐fat diet. While females consumed more ethanol than males, alcohol consumption was able to improve glucose tolerance and increase anxiety in both sexes. Lastly, females were more resistant to the physiological changes caused by high‐fat diet than males, as females consuming high‐fat diet exhibited decreased insulin secretion, less change to brain‐derived neurotrophic factor levels, and better glucose tolerance than males consuming high‐fat diet.ConclusionThese results suggest that the response to high‐fat diet and alcohol consumption is sex dependent and that males are more affected both behaviorally and physiologically by high‐fat diet compared to females.

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ObJeCTIVe: both the consumption of high-fat diets and exercise are known to produce alterations in metabolism and behavior. This study focuses on the effects of a change to a lowfat diet from a high-fat diet and voluntary exercise on obesity, type-2 diabetic-like symptoms, and locomotor behavior in male C57BL/6J mice. DeSIgN: Mice were initially given either a high-fat diet or regular chow, along with a cage with a running-wheel to mimic exercise, or one without, to determine to what extend exercise affects these symptoms. Then half of the mice given a high-fat diet were switched to regular chow to ascertain if the switch in diet would improve type-2 diabetic-like and obesity symptoms. ReSUlTS: Wheel-running alone produced an improvement in insulin in mice continuously fed a high-fat diet (p=0.006), but running-wheels did not produce any further improvements in mice with regular chow replacement (p=0.999) or in controls (p=0.996). Replacement of a high-fat diet with regular chow led to physiological improvements in insulin (p=0.012) and leptin (p <0.001), glucose tolerance (p <0.001), and obesity (p <0.001), more so than exercise alone. Mice consuming a high-fat diet without a wheel exhibited reduced home-cage activity compared to controls after the diet switch (p=0.030), while no reduction was found in running-wheel activity between high-fat diet and regular chow consuming mice after switching diets (p=0.516). CONCLUSIONS: These results suggest that exercise is only partially beneficial to improving health outcomes in mice consuming a high-fat diet, whereas incorporating a better diet, even without exercise, improves quality of health and can suppress T2DM symptoms and related conditions more so than exercise alone.

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