Eleanna O. De Filippis, M.D., Ph.D.

This study is being done to better understand the relationship between inflammation in your AT, abnormal deposition of fat around your liver and how this affects its appearance and function and ultimately insulin resistance.

The purpose of this study is to find the inheritable changes in genetic makeup that are related to the development of type 2 diabetes in Latino families.

The objective of this study is to assess the metabolic effect of systemic inhibition of IL-4 signaling on insulin sensitivity in patients with atopic dermatitis by comparing in vivo evaluations of insulin sensitivity in subjects on dupilumab vs. subjects matched for similar adiposity, with atopic dermatitis, but without dupilumab therapy.

This study is being done to better understand the relationship between inflammation and insulin resistance in your Adipose (fat) Tissue .

To determine whether EOS recruitment in AT is impaired during obesity. Therefore, we hypothesize that chronic, low-grade inflammation of AT initiates epigenetic modifications in EOS and/or in AT, thereby impairing the recruitment of eosinophils.

This protocol is being conducted to determine the mechanisms responsible for insulin resistance, obesity and type 2 diabetes.

This study aims to assess adipose tissue-eosinophil content and adiopose tissue metabolism 3 months after endoscopic gastroplasty weight loss procedure.

There are two purposes for this project.

• One purpose of this project is to develop information about Latinos in the Maricopa County area who may be interested in participating in future research studies about health.

• A second purpose is that researchers at Mayo Clinic are developing a new research resource called a Biobank. A Biobank is a collection of blood samples and other information. Participants in the Biobank provide samples of blood, complete a health questionnaire, and allow access to medical records now and in the future. A Biobank is as a library for researchers; instead of having to look for volunteers for each new project, researchers can use samples from the Biobank as well as share information already collected.

The goal of this proposal is to highlight a potentially pivotal role of EOS in human metabolism. This pilot project will initiate future investigations demonstrating AT-EOS involvement in insulin sensitivity (IS). These data will be innovative, and of great clinical importance in the era of FDA-approved biologic drugs treating many eosinophilic-driven diseases. These drugs lack comprehensive assessment of their impact on metabolic health. Our central hypothesis is that elimination of circulating EOS will negatively affect systemic inflammation and plasma adipokines levels (low adiponectin, high leptin) resulting in impaired glucose metabolism, all central features of IR. Our team is well suited to perform these studies based on our experience in measuring in vivo IS in humans. We propose the following specific aim:

Aim 1: To determine the metabolic effects of decreasing circulating EOS in healthy subjects. Mepolizumab is an FDA-approved drug that selectively reduces circulating EOS12. We have an IND exemption approved by the FDA to use mepolizumab in healthy subjects to test our central hypothesis. This pilot study will lay the foundation to further investigate the impact of Mepolizumab on AT-EOS content and tissue homeostasis (NIH R01 proposal). Elucidating a role for EOS in metabolic homeostasis will advance the role of future immunotherapeutic agents in the treatment of IR and prevent development of obesity-related complications.