Modulation of foraging-like behaviors by cholesterol-FGF19 axis

Area of Science:

• Neuroscience
• Metabolic regulation
• Behavioral science

Background:

• Foraging behavior is crucial for feeding and metabolic programming.
• Neuronal circuits control foraging, but dietary and hormonal influences are unclear.

Purpose of the Study:

• To investigate how dietary cholesterol affects foraging and locomotor activity.
• To elucidate the roles of Agouti-related protein (AgRP) and fibroblast growth factor 19 (FGF19) in mediating these effects.

Main Methods:

• Assessed locomotor and exploratory activity in mice under varying dietary cholesterol conditions.
• Administered FGF19 centrally and measured behavioral responses.
• Examined intestinal Fgf15 expression in response to dietary cholesterol.

Main Results:

• High dietary cholesterol suppressed locomotor activity, partly mediated by AgRP.
• Dietary cholesterol increased intestinal Fgf15 expression.
• Central FGF19 administration reduced exploratory activity, mimicking cholesterol's suppressive effect.

Conclusions:

• Dietary cholesterol suppresses foraging and exploratory behaviors through AgRP neurons and FGF19 signaling.
• FGF19 in the brain may mediate the anxiogenic effects of dietary cholesterol.
• Dietary cholesterol and FGF15/19 act as satiety signals to the brain, reducing foraging.