Metabolic adaptation to calorie restriction

When a person consumes significantly fewer calories over an extended period, their body produces higher levels of hunger-related signals and lowers its resting energy expenditure.

When female mice eat fewer calories at 22°C, their core body temperature drops and stays lower; this drop does not occur when they are kept at 30°C, and the temperature change correlates with most metabolic shifts in the hypothalamus and some in the rest of the body.

When mice are housed at 30°C, the metabolic changes caused by eating fewer calories are significantly smaller in the brain and blood compared to when they are housed at 22°C. This means that standard lab temperatures make the body's response to dieting appear stronger than it would be under normal physiological conditions.

In female mice, a natural brain peptide called leucine enkephalin rises when food intake is reduced at cooler temperatures (22°C) but not at warmer temperatures (30°C). Injecting this peptide directly into the hypothalamus changes body temperature, showing it directly influences temperature regulation during calorie restriction.

In female mice kept at 22°C, reducing calorie intake raises nitric oxide levels in the hypothalamus through the citrulline-nitric oxide cycle, and blocking nitric oxide production stops the drop in body temperature that normally occurs with reduced calorie intake.

In female mice, keeping the environment at 30°C reduces the metabolic changes caused by eating fewer calories, while keeping them at 22°C creates cold stress that changes how their bodies respond to calorie restriction.