FGF21 Regulates Sweet and Alcohol Preference.

Area of Science:

• Endocrinology
• Neuroscience
• Metabolic Regulation

Background:

• Fibroblast growth factor 21 (FGF21) is a metabolic hormone involved in energy homeostasis.
• Human genetic variations in the FGF21 gene correlate with macronutrient intake preferences.
• FGF21 is induced by metabolic stresses like ketogenic and high-carbohydrate diets.

Purpose of the Study:

• To investigate the effect of FGF21 administration on nutrient preference and reward behaviors.
• To explore the neural mechanisms underlying FGF21's influence on preference.

Main Methods:

• Administration of FGF21 to mice and cynomolgus monkeys.
• Assessment of sweet, alcohol, and macronutrient preferences.
• Analysis of central nervous system co-receptor involvement (β-Klotho).
• Measurement of dopamine concentrations in the nucleus accumbens.

Main Results:

• FGF21 administration significantly reduced sweet and alcohol preference in mice.
• Sweet preference was also reduced in cynomolgus monkeys following FGF21 administration.
• These effects in mice were dependent on the FGF21 co-receptor β-Klotho in the central nervous system.
• FGF21 administration correlated with decreased dopamine levels in the nucleus accumbens.

Conclusions:

• FGF21 plays a role in regulating nutrient and alcohol preference.
• Central nervous system mechanisms, involving β-Klotho and dopamine, mediate FGF21's effects on preference.
• FGF21 analogs, currently in clinical trials for metabolic disorders, may also influence reward behaviors in humans.