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Hematopoietic ABCA1 and ABCG1 regulate monocytosis, macrophage inflammation and insulin resistance in diet-induced obesity

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Introduction: Insulin resistance is a major metabolic defect in obesity and is associated with increased risk of type-2 diabetes and cardiovascular disease (CVD). Recent studies indicate that the feed-forward loop between monocytosis and adipose macrophage accumulation plays a key role in driving adipose tissue inflammation and insulin resistance. It has also been shown that hematopoietic ATP-binding cassette transporter A1 (ABCA1) or both ABCA1 and ABCG1 deletion promotes monocytosis and increases macrophage inflammation, suggesting that hematopoietic ABCA1 along and both ABCA1 and ABCG1 may play important roles in the feed-forward loop between monocytosis and adipose tissue inflammation. We hypothesize that altering hematopoietic ABCA1 or both ABCA1 and ABCG1 expression would affect (I.E. deletion would enhance and overexpression would block) this feed-forward loop between monocytosis and adipose tissue inflammation, thereby affecting insulin resistance.

Purpose: Determine the effects and mechanisms of altering hematopoietic ABCA1 and ABCG1 expression on monocytosis, macrophage inflammation and insulin resistance in diet-induced obesity.