Uncoupling Protein-1 Modulates Anxiety-Like Behavior in a Temperature-Dependent Manner

Area of Science:

• Neuroscience
• Metabolic Disorders
• Psychiatry

Background:

• A bidirectional link exists between metabolic and psychiatric disorders.
• The molecular mechanisms underlying this interaction are not fully understood.
• Uncoupling protein 1 (UCP-1) is a key metabolic regulator in brown adipose tissue (BAT).

Purpose of the Study:

• To investigate the role of UCP-1 in emotional behavior.
• To explore UCP-1's function as a modulatory interface between metabolic and psychiatric conditions.
• To examine the impact of UCP-1 deficiency on anxiety- and depression-related behaviors under varying temperatures.

Main Methods:

• Utilized UCP-1 knock-out (KO) mice and wild-type (WT) littermates.
• Assessed anxiety- and depression-related behaviors at thermogenic (23°C) and thermoneutral (29°C) conditions.
• Measured neural and endocrine stress mediators, and fibroblast-growth factor-21 (FGF-21) levels.

Main Results:

• UCP-1 KO mice exhibited enhanced anxiety-related behavior exclusively under thermogenic conditions.
• No significant differences in neural/endocrine stress mediators were observed.
• Integrated stress response activation and elevated FGF-21 levels were noted in UCP-1 KO mice.
• FGF-21 manipulation and BAT removal did not alter the observed behavioral phenotype.

Conclusions:

• UCP-1 plays a novel role in regulating emotions, acting as an inhibitory constraint on anxiety-related behavior.
• This UCP-1 function is temperature-dependent and likely mediated centrally in the brain.
• The findings suggest UCP-1's involvement in fear regulation, independent of its role in BAT thermogenesis.