The discovery of the endocrine role of adipose tissue in the regulation of energy metabolism has significantly advanced our understanding of the mechanisms for the development of insulin resistance and type 2 diabetes. The recent progress has focused on the role of adipose tissue inflammation and endocrine dysfunction in obesity and insulin resistance. However, how adipocyte dysfunction is linked to adipose tissue inflammation and systemic insulin resistance is far from understood: Insulin sensitivity is modulated by the complex mechanisms involving many adipokines and pro-inflammatory cytokines.
The roles of anti-inflammatory cytokines in glucose metabolism and insulin resistance have been poorly identified. Lipocalin 2, a secreted protein previously known to possess anti-inflammatory properties, is a recently discovered adipokine. Based on preliminary data from our laboratory, we are the first to discover that lipocalin 2 appears to possess a pivotal function in insulin sensitization perhaps linked to its anti-inflammatory activity.
Our central hypothesis is that adipose lipocalin 2 plays a role in mediating adipocyte dysfunction-induced systemic insulin resistance through the mechanism involving adipose inflammation and insulin resistance.
We proposed three aims to discover the biological significance of lipocalin 2 and to define the role and mechanism of lipocalin 2 in the regulation of insulin resistance and inflammation. Both loss and gain of function strategies will be used to test the hypothesis in mice and 3T3-L1 adipocytes. Recombinant lipocalin 2 and RNAi-mediated gene silencing will be used to enhance or decrease lipocalin 2 action, respectively.
The outcomes from these studies will provide new insight into the role of lipocalin 2 as a novel player in adipose tissue inflammation and insulin resistance.
ZEB1 and the Development of Obesity
Oxyntomodulin and the Regulation of Non-Exercise Activity Thermogenesis
Hypothalamic Acyl-CoA Metabolism and Food Intake Regulation
Parents as the Agent of Change for Childhood Obesity
Identifying Novel Roles of Lipocalin 2 in Insulin Action and Glucose Metabolism
GIRK$: A New Obesity Gene?
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