Obesity is characterized by dysregulated homeostatic mechanisms resulting in positive energy balance, yet when this dysregulation occurs is unknown. We assessed the time course of alterations to behaviors promoting weight gain in male and female mice switched to obesogenic 60% or 45% high fat diet (HFD). Switching mice to obesogenic diets promotes transient bouts of hyperphagia during the first 2 weeks followed by persistent caloric hyperphagia. Energy expenditure increases but not sufficiently to offset increased caloric intake, resulting in a sustained net positive energy balance. Hyperphagia is associated with consumption of calorically larger meals (impaired satiation) more frequently (impaired satiety) particularly during the light-cycle. Running wheel exercise delays weight gain in 60% HFD-fed male mice by enhancing satiation and increasing energy expenditure. However, exercise effects on satiation are no longer apparent after 2 weeks, coinciding with weight gain. Thus, exposure to obesogenic diets engages homeostatic regulatory mechanisms for ∼2 weeks that ultimately fail, and consequent weight gain is characterized by impaired satiation and satiety. Insights into the etiology of obesity can be obtained by investigating changes to satiation and satiety mechanisms during the initial ∼2 weeks of HFD exposure.
What is already known about this subject?: Obesity is associated with dysregulated homeostatic mechanisms.Increased caloric consumption contributes to obesity.Obese rodents tend to eat larger, more frequent meals.
What are the new findings in your manuscript?: Exposure to obesogenic diets promotes transient attempts to maintain weight homeostasis.After ∼2 weeks, caloric hyperphagia exceeds increased energy expenditure, promoting weight gain.This is associated with consumption of larger, more frequent meals.
How might your results change the direction of research or the focus of clinical practice?: Our findings suggest that molecular studies focusing on mechanisms that regulate meal size and frequency, particularly those engaged during the first ∼2 weeks of obesogenic diet feeding that eventually fail, can provide unique insight into the etiology of obesity.