Prolonged fasting induces long-lasting metabolic consequences in mice

Area of Science:

• Metabolic Adaptations
• Epigenetics
• Animal Physiology

Background:

• Animals exhibit acute physiological adjustments to endure fasting.
• Long-term metabolic adaptations following severe fasting remain largely uncharacterized.

Purpose of the Study:

• To investigate long-term metabolic adaptations after prolonged fasting.
• To explore the role of hypothalamic epigenetic changes in these adaptations.

Main Methods:

• Adult male mice underwent 48-hour fasting and subsequent refeeding.
• Assessed body composition, energy expenditure, respiratory exchange ratio, and locomotor activity.
• Analyzed hypothalamic gene expression (Pomc, epigenetic modifiers) and histone acetylation.

Main Results:

• Fasting led to weight loss, but refeeding resulted in adiposity above baseline with incomplete recovery of lean mass and energy expenditure.
• A fasting/refeeding cycle induced persistent suppression of Pomc mRNA and altered expression of histone deacetylases and DNA methyltransferases.
• Previous fasting experience altered responses to subsequent fasting/refeeding cycles and high-fat diet challenges, including increased calorie intake and fat mass gain.

Conclusions:

• Cumulative prolonged fasting episodes induce long-lasting metabolic adaptations in mice.
• Hypothalamic epigenetic changes are associated with these persistent metabolic alterations.
• Prior fasting experience influences metabolic and behavioral responses to dietary challenges.