Evidence of persistent hunger following dietary weight loss in mice

Over 40% of adults in the United States struggle with obesity, and nearly half have attempted weight loss, yet most efforts result in weight regain. Rodent models have been used to study the physiological drivers of this phenomenon, but it remains unclear whether they exhibit weight regain after sustained weight loss. To address this, we developed a mouse model of reversed dietary obesity (ReDO) that demonstrates susceptibility to weight regain following sustained weight loss. Male diet-induced obese (DIO) mice were calorically restricted (CR) until weight-matched to controls, then pair-fed for 0, 8, or 28 days, or chronically. Upon return to ad libitum feeding, all ReDO groups displayed persistent hyperphagia relative to controls and chronically pair-fed mice. Variability in body weight regain among pair-fed ReDO mice correlated with initial 4-week weight gain on a high-fat diet. This study introduces a mouse model for mechanistic studies of weight loss-associated hyperphagia and provides a potential predictor of weight regain.