Department

School of Pharmacy

First Advisor

Guanglong He

Description

Obesity is highly prevalent and causes diseases such as diabetes. One contributing factor is chronic inflammation. The adaptor protein caspase recruitment domain-containing protein 9 (CARD9) is involved in the innate immune response by activating pro-inflammatory cytokines in obesity. Another contributing factor is basal and stimulated lipolysis. The end product, free fatty acids, accumulate in the body and result in insulin resistance (IR) and diabetes.

From our previous study, it was found that high fat diet (HFD) induces IR. A CARD9-/- animal model on HFD had improved but not completely ameliorated IR suggesting other factors are involved. One hypothesis is that both inflammation and adipocyte lipolysis contribute to IR. The goal of this project is to determine if CARD9 has an effect on adipocyte lipolysis and related lipid toxicity.

C57BL/6 wild-type and CARD9-/- mice were fed on a normal diet (ND) or a HFD for five months. Western immunoblotting analyses were performed on visceral adipose tissue. The data indicates that p-perilipin, perilipin, ATGL, p-JNK, and p62 were down-regulated in HFD, but little difference was seen between wild-type and CARD9-/- groups. LC3BII/I appears to be up-regulated in HFD, with little difference between wild-type and CARD9-/- groups. Preliminary data shows no change for p-HSL p-AKT, or p-ERK.

To date, our conclusion is HFD increases basal and decreases stimulated lipolysis in visceral adipose tissue, but CARD9 does not have a large effect. This indicates that the difference in insulin sensitivity seen in the CARD9-/- model is likely due to adipocyte lipolysis.

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Effect of CARD9 on adipocyte lipolysis

Obesity is highly prevalent and causes diseases such as diabetes. One contributing factor is chronic inflammation. The adaptor protein caspase recruitment domain-containing protein 9 (CARD9) is involved in the innate immune response by activating pro-inflammatory cytokines in obesity. Another contributing factor is basal and stimulated lipolysis. The end product, free fatty acids, accumulate in the body and result in insulin resistance (IR) and diabetes.

From our previous study, it was found that high fat diet (HFD) induces IR. A CARD9-/- animal model on HFD had improved but not completely ameliorated IR suggesting other factors are involved. One hypothesis is that both inflammation and adipocyte lipolysis contribute to IR. The goal of this project is to determine if CARD9 has an effect on adipocyte lipolysis and related lipid toxicity.

C57BL/6 wild-type and CARD9-/- mice were fed on a normal diet (ND) or a HFD for five months. Western immunoblotting analyses were performed on visceral adipose tissue. The data indicates that p-perilipin, perilipin, ATGL, p-JNK, and p62 were down-regulated in HFD, but little difference was seen between wild-type and CARD9-/- groups. LC3BII/I appears to be up-regulated in HFD, with little difference between wild-type and CARD9-/- groups. Preliminary data shows no change for p-HSL p-AKT, or p-ERK.

To date, our conclusion is HFD increases basal and decreases stimulated lipolysis in visceral adipose tissue, but CARD9 does not have a large effect. This indicates that the difference in insulin sensitivity seen in the CARD9-/- model is likely due to adipocyte lipolysis.