Adiponectin and Toll-Like Receptor 4: Important Adipocyte Modulators of Systemic Glucose and Lipid Metabolism




Tao, Caroline

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As a global epidemic, the prevalence of obesity and its complications have increased rapidly over the past few decades. Obesity, characterized by excessive amount of body fat accumulation, is a strong predictor to various major health conditions such as type 2 diabetes and cardiovascular disease. Two hallmark features of an unhealthy hypertrophic adipose tissue are decreased adiponectin secretion and increased adipose tissue inflammation. Released almost exclusively from adipocytes, adiponectin exerts potent insulin sensitizing effects on peripheral tissues. Using a series of inducible mouse models, we identified an adipocyte-specific regulatory mechanism for adiponectin expression and release. In addition to the role in maintaining glucose homeostasis, adiponectin is also found to exert anti-fibrotic, anti-inflammatory and anti-apoptotic properties in numerous other cell types. In the obese state, decreased adiponectin secretion contributes to increased adipose tissue inflammation. Toll-like receptor 4 is an important mediator of inflammatory response found abundantly on the cell surface of adipocytes. In this study, using an adipocyte- specific deletion, we demonstrated a dichotomous effect of Toll-like receptor 4 on adipose tissue functionality. Toll-like receptor 4 is essential for proper adipose tissue remodeling to promote healthy expansion during long term high-fat diet exposure. In contrast, toll-like receptor 4 can also be a mediator of insulin resistance during an acute challenge with saturated fatty acids. In summary, my studies highlight a tight in vivo regulation of adiponectin secretion and demonstrate the role of adipocyte toll-like receptor 4 in modulating systemic glucose homeostasis during the development of obesity.

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