Increased insulin sensitivity despite lipodystrophy in Crebbp heterozygous mice

Area of Science:

• Molecular Biology
• Metabolism
• Genetics

Background:

• The cAMP response element binding protein (CREB) binding protein (CBP) acts as a transcriptional co-activator for various factors.
• The precise physiological roles of CBP remain largely undefined.
• CBP facilitates transcription through histone acetylation and recruiting co-activators like SRC-1.

Purpose of the Study:

• To investigate the physiological functions of CBP using a loss-of-function mouse model.
• To elucidate CBP's role in metabolic regulation and energy balance.

Main Methods:

• Analysis of heterozygous CBP-deficient mice (Crebbp+/-) due to embryonic lethality of null mutants (Crebbp-/-).
• Assessment of body weight, adipose tissue mass, insulin sensitivity, glucose tolerance, and response to a high-fat diet.
• Measurement of leptin sensitivity and serum adiponectin levels.

Main Results:

• Crebbp+/- mice exhibited significantly reduced white adipose tissue (WAT) weight.
• Despite lipodystrophy, these mice displayed enhanced insulin sensitivity and glucose tolerance.
• Crebbp+/- mice were fully protected against weight gain on a high-fat diet and showed increased leptin sensitivity and adiponectin levels.

Conclusions:

• CBP deficiency leads to reduced WAT mass and improved metabolic parameters, including insulin sensitivity and glucose tolerance.
• Increased adiponectin and leptin sensitivity in CBP-deficient mice may contribute to their metabolic phenotype.
• CBP appears to function as a critical regulator, or 'master-switch,' controlling the balance between energy storage and expenditure.