Food Restriction in Mice Induces Food-Anticipatory Activity and Circadian-Rhythm-Related Activity Changes

Abstract

Anorexia nervosa (AN) is characterized by emaciation, hyperactivity, and amenorrhea. To what extent AN-related symptoms are due to food restriction or neuronal dysfunction is currently unknown. Thus, we investigated the relevance of food restriction on AN-related symptoms. Disrupted circadian rhythms are hypothesized to contribute to the pathophysiology of AN. Starvation was induced by restricting food access in early adolescent or adolescent mice to 40% of their baseline food intake until a 20% weight reduction was reached (acute starvation). To mimic chronic starvation, the reduced weight was maintained for a further 2 weeks. Locomotor activity was analyzed using running wheel sensors. The circadian-rhythm-related activity was measured using the tracking system Goblotrop. Amenorrhea was determined by histological examination of vaginal smears. All cohorts showed an increase in locomotor activity up to 4 h before food presentation (food-anticipatory activity, FAA). While amenorrhea was present in all groups except in early adolescent acutely starved mice, hyperactivity was exclusively found in chronically starved groups. Adolescent chronically starved mice showed a decrease in circadian-rhythm-related activity at night. Chronic starvation most closely mimics AN-related behavioral changes. It appears that the FAA is a direct consequence of starvation. The circadian activity changes might underlie the pathophysiology of AN.

Starvation in Mice Induces Liver Damage Associated with Autophagy

“…We focused on the starvation-induced changes in the liver, as this organ plays an important role in nutritional storage in conditions of malnutrition. To analyze the pathophysiology of the liver, we used a murine SIH model that mimics the core features of AN, such as body weight loss, hyperactivity, and amenorrhea [ 12 ]. In this study, both acute and chronic starvation induced hyperactivity in all groups, which might be an excessive drive to forage in mice.…”

“…To unravel this pathophysiology, we used the murine starvation-induced hyperactivity (SIH) model, which mimics the somatic consequences of AN, such as body weight loss, hyperactivity, and amenorrhea, as well as endocrine changes [ 12 , 13 , 14 , 15 , 16 ]. To mimic chronic starvation, a fixed body weight loss was induced, increasing the comparability of results [ 14 ].…”

Glial cell changes in the corpus callosum in chronically-starved mice

“…Female C57BL/6J mice (n = 60 animals, 4-weeks old referred to as early adolescents and 8 weeks-old referred to adolescents) were purchased from Janvier Labs (Le Genest-Saint-Isle, France) as part of a large cohort study [ 11 , 25 ] and housed under a 12/12 h light/dark cycle and a temperature of 22 ± 2 °C. The beginning of the light phase was at 6 AM.…”

“…In each starvation phase, the mice were allowed free access to their calculated amount of food for the following 24 h. Throughout the various phases of starvation, the control group animals consistently had unrestricted access to food. To investigate running activity (previously described [ 11 ]), we utilized running wheels (11.5 cm in diameter) attached to the top of the cages. The running distance was evaluated every hour using an activity program (VitalView Activity 1.4, STARR Life Science Corp.).…”

“…To investigate the cellular basis of starvation-induced changes in the brain, we used a semi-starvation-induced hyperactivity (SIH) mouse model involving a limited amount of food and access to running wheels [ 10 , 11 ]. In this model, mice received reduced food intake until a 20% weight reduction was reached (one-week phase defined as acute starvation) and maintained for two weeks (chronic starvation).…”