Uncoupling protein-1 expression does not protect mice from diet-induced obesity

Area of Science:

• Metabolic phenotyping
• Thermogenesis
• Obesity research

Background:

• Uncoupling Protein 1 (UCP1) is key in brown adipose tissue (BAT) thermogenesis.
• Novel reporter mouse models are needed to study UCP1 function in energy balance.

Purpose of the Study:

• To metabolically phenotype a novel UCP1-LUC-iRFP713 knock-in reporter mouse model.
• To investigate the role of UCP1 in cold-induced thermogenesis and protection against weight gain.

Main Methods:

• Generation and metabolic phenotyping of UCP1-LUC-iRFP713 knock-in reporter mice.
• Assessment of UCP1 expression in vivo and in vitro.
• Evaluation of thermogenic capacity following norepinephrine stimulation and cold exposure.
• Analysis of body mass changes under different dietary conditions and ambient temperatures.
• Investigation of weight loss following beta-3 adrenergic receptor agonist (CL316,243) administration.

Main Results:

• Homozygous knock-in mice exhibited reduced UCP1 content, blunted thermogenic capacity, and increased cold sensitivity.
• No significant body mass differences were observed across genotypes without pharmacological UCP1 activation.
• Pharmacological activation of UCP1 led to greater weight reduction in wild-type mice compared to knock-in mice.
• Impaired cold-induced thermogenic capacity did not increase susceptibility to diet-induced obesity.

Conclusions:

• Intact UCP1 expression is essential for cold-induced thermogenesis.
• UCP1 presence alone does not protect against diet-induced obesity.
• Pharmacological activation of brown fat is necessary to promote negative energy balance in diet-induced obese mice.