The Centers for Disease Control & Prevention estimates that at least one-third of the U.S. population is considered obese (34.9%). Recent studies, however, suggest that these statistics are a huge underestimate and fail to account for an additional 16% of obese individuals in the United States. Obesity is a state of chronic low-grade inflammation that influences various organs, such as white adipose tissue, brown adipose tissue, pancreas, liver, brain, muscle, and the intestine. The far-reaching medical consequences of obesity-associated inflammation include diabetes, cardiovascular disease, hepatic steatosis, and even cancer. Based on these alarming statistics and detrimental consequences, obesity has become a major global health concern. Therefore, there is an urgent need for development of effective therapeutic interventions. In this regard, our conjugates of Lacto-N-fucopentaose III (LNFPIII) linked to a 40kDa dextran backbone (LNFPIII-Dex) have been shown to be anti-inflammatory in vivo and therapeutic for several inflammation-based conditions. In particular, we have shown that LNFPIII-Dex alleviates insulin resistance and hepatosteatosis in a model of diet-induced obesity. Furthermore, LNFPIII-Dex promotes M2 macrophage polarization in vivo and induces lipolysis in hepatocytes. In Aim 1 of this proposal, we will utilize an in vitro cell culture model to determine if LNFPIII-Dex acts directly on adipocytes or indirectly via adipocyte-macrophage crosstalk. In Aim 2, we will evaluate the organ-specific therapeutic benefits of LNFPIII-Dex in an in vivo model of diet-induced obesity. We hope that results from these experiments will lead to a novel therapeutic and/or new molecular targets for metabolic disease.
|Program type||Predoctoral Fellowship|
|Effective start/end date||01/01/2017 → 12/31/2018|