Deficiency of TNFalpha converting enzyme (TACE/ADAM17) causes a lean, hypermetabolic phenotype in mice

Area of Science:

• Metabolism and Endocrinology
• Neuroscience
• Molecular Biology

Background:

• Energy homeostasis is regulated by the central nervous system integrating signals for food intake and energy expenditure.
• The role of TNFalpha converting enzyme (TACE) in energy balance remains largely unexplored.

Purpose of the Study:

• To investigate the role of TACE in the regulation of energy homeostasis.
• To characterize the metabolic phenotype of TACE-deficient mice.

Main Methods:

• Analysis of adult homozygous TACE-deficient mice (Tace(DeltaZn/DeltaZn)).
• Assessment of food intake, energy expenditure, body composition, and hypothalamic neuronal responses.
• Measurement of uncoupling protein-1 (UCP1) levels in brown adipose tissue.

Main Results:

• TACE-deficient mice exhibit severe hypermetabolism and a lean phenotype without increased food intake.
• Hypothalamic arcuate nucleus neurons show normal responses to leptin and fat mass.
• Elevated UCP1 in brown adipose tissue suggests increased sympathetic outflow in TACE-deficient mice.

Conclusions:

• TACE deficiency leads to a novel form of hypermetabolism linked to increased energy expenditure.
• The findings implicate TACE in the regulation of sympathetic nervous system activity and energy balance.
• TACE plays a significant role in maintaining energy homeostasis.