The Research

Chronic inflammation contributes toward the development of a wide range of diseases including those related to obesity.  Our lab is currently focused on understanding how n-3 polyunsaturated fatty acids (PUFA), which are a major component of the anti-inflammatory Mediterranean diet, can potentially control differing inflammatory responses. Key projects focused on fatty acid metabolism, inflammation, and obesity are described below:

Establishing the cellular targets and molecular mechanisms by which long chain n-3 PUFAs and their downstream metabolites boost humoral immunity in obese rodents and humans with obesity. One major complication of obesity, that is often overlooked, is increased susceptibility to infections and poor responses to vaccinations. We are investigating the novel hypothesis that dietary deficiencies in n-3 PUFAs, due to industrialization of food production, is contributing toward increased susceptibility to viral infections and inflammation in individuals with obesity. We have identified specific deficiencies in n-3 PUFA-derived metabolites in mouse models and very recently in humans. Furthermore, n-3 PUFA administration to obese mice improves B cell-driven antibody production upon influenza infection. Currently, we are translating our mouse studies by determining if n-3 PUFAs and their downstream metabolites are specifically deficient in individuals with obesity upon influenza vaccination. The long-term goal of this work is to drive new precision clinical trials focused on improving humoral immunity and inflammation in individuals with obesity using dietary and pharmacological approaches.

Investigate how metabolites derived from n-3 PUFAs improve pulmonary inflammation in the context of environmental exposures. A relatively new project in the lab is to understand how obesity and environmental exposures impair pulmonary outcomes. This work is timely given the current COVID-19 pandemic in which individuals with obesity are at increased risk for pulmonary complications.  We are investigating how high fat diets, in absence and presence of ozone exposure, impair the pulmonary lipidome thereby pulmonary macrophage polarization and function. Our approach relies on newly constructed knockout mice and cell culture studies. We are also studying the use of dietary n-3 PUFAs to prevent chronic inflammation. These studies involve experiments focused on lipid raft biophysical organization using imaging approaches.  The research is in collaboration with Dr. Kym Gowdy at the Ohio State University. The significance of this work for public health is that we aim to develop effective dietary strategies for preventing pulmonary inflammation in select clinical populations and geographical areas.

Activation of the hydroxyeicosapentaenoic acid pathway for improving aspects of glucose homeostasis. We have discovered that select metabolites synthesized from the n-3 PUFA eicosapentaenoic acid (EPA) known as hydroxyeicosapentaenoic acids (HEPEs) are dramatically lowered in obese male and female mice.  Therefore, we are investigating how these deficiencies contribute toward poor glucose homeostasis and chronic inflammation in response to obesity and type 2 diabetes. We are using a combination of approaches for our studies, which include the use of tissue-specific knockout mouse models, diversity outbred mice (to study the role of the host genome on EPA metabolism), and clinical studies. Collectively, this project will contribute toward better designed clinical trials that implement personalized administration of EPA and/or HEPEs as an effective means of preventing impairments to glucose homeostasis driven by a western obesogenic diet.

Investigate the anti-inflammatory properties of palmitoleic acid in humans. Palmitoleic acid is a fatty acid that is hypothesized to have immunomodulatory properties. The fatty acid is found in low abundance in human circulation and is largely consumed from a few select food sources. We have an ongoing clinical trial in which we are administering two different doses of palmitoleic acid to determine if we can improve chronic inflammation in subjects that have elevated C-reactive protein. This double-blind randomized placebo-controlled trial is registered with clinicaltrials.gov. Secondary outcomes from this study include additional inflammatory markers, association between food intake and food recalls, and circulating blood levels of palmitoleic acid.  This project contributes toward public health by providing key insight about palmitoleic acid, a poorly studied fatty acid that is increasingly recognized to have anti-inflammatory properties. If successful, this work will set the basis for a larger clinical trial.