Adipose tissue-specific Yap knockout exacerbates diet-induced obesity through suppression of lipolysis

Area of Science:

• Cellular Biology
• Metabolic Research
• Obesity Studies

Background:

• YAP (Yes-associated protein) is a crucial regulator of diverse cellular functions, including proliferation, differentiation, and apoptosis.
• While YAP is known to inhibit adipogenesis in vitro, its precise role in the development of obesity remains incompletely understood.

Purpose of the Study:

• To investigate the in vivo role of YAP in adipose tissue and its contribution to obesity.
• To elucidate the molecular mechanisms by which YAP influences metabolic processes related to obesity.

Main Methods:

• Generation of an adipose tissue-specific Yap knockout mouse model (YapaKO).
• Assessment of obesity phenotype in YapaKO mice fed a high-fat diet.
• Analysis of lipolytic activity, gene expression of lipolytic enzymes (ATGL, HSL), and physiological responses to fasting and cold exposure.

Main Results:

• Male YapaKO mice exhibited an exacerbated high-fat diet-induced obesity phenotype compared to controls, while female mice did not.
• Reduced expression of key triglyceride lipolytic enzymes (ATGL, HSL) was observed in YapaKO mice, leading to suppressed lipolytic activity.
• Impaired fasting-induced lipolysis resulted in reduced circulating free fatty acids, compromised thermoregulation after cold exposure, and diminished exercise capacity in fasted male mice.

Conclusions:

• YAP functions as a physiological regulator of lipolysis within adipose tissue.
• Activation of YAP in adipose tissue promotes lipolysis, potentially serving as a therapeutic strategy to mitigate obesity.