The Sabri Ülker Center’s Translational Research Efforts

This year, we have made important progress towards our translational aspirations as one of our Center members, Mehmet Furkan Burak, MD recently received a $2.5M grant, and launched a double-blind clinical trial with Massachusetts General and Brigham and Women’s Hospital. In this trial, Dr. Burak will test the potential benefits of palmitoleic acid (POA) compared to a placebo in human subjects, focusing on insulin sensitivity, glucose production, and fat formation. One of the most exciting aspects of reaching this stage is the fact that POA was discovered in our Center. POA is a monounsaturated fatty acid naturally found in the body’s adipose tissue, but is also, in specific foods such as certain fish and macadamia nuts. Although it can be consumed through diet, POA contains other complex oils such as palmitic acid, which is generally harmful to the body and counteracts its benefits. Through a purification technique, palmitic acid is separated and thus, creates clinical-grade POA, used in clinical testing.

The initial findings began “at the bench” by exploring a hypothesis that resulted from years of studying fatty acid binding proteins. Our laboratory found that when these proteins are blocked in mice, they start producing higher levels of POA in adipocytes, and when delivered into circulation, the animals do not exhibit any of the diseases associated with obesity. The discovery of POA was reported in the manuscript “Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism” published in Cell and revealed a novel, lipidmediated endocrine network as well as demonstrating that adipose tissue uses lipokines such as C16:1n7-palmitoleate, to communicate with distant organs and regulate systemic metabolic homeostasis. Supplementation of POA in mice improved insulin sensitivity and reversed the lipogenic gene expression. Now, the same methods described in this paper and conducted in our lab are being reformulated for testing in humans, a real-life transition “from bench” to “bedside.”

How will this research be safely translated to clinical trials?

The study will recruit overweight and obese individuals (BMI 25-40) with mild insulin resistance, prediabetes, and/or impaired glucose tolerance. After an initial study screening visit confirms eligibility for the study, an oral glucose tolerance test (OGTT) will be administered to provide for stratified randomization, for better homogeneity between POA and placebo groups. The study aims to have 40 participants, which will consist of 2 main overnight visits consisting of an insulin clamp procedure and a mixed meal tolerance test the night prior; participants will also have a liver MRI and DEXA scan during these two visits. Participants will be asked to consume a palmitoleic acidminimized diet for 10 weeks, which will start 2 weeks before the first overnight visit. This research study will compare insulin sensitivity before, and 8 weeks after taking POA vs placebo in the same individuals. After the first overnight visit, participants will be given either POA or placebo capsules to be taken daily for 8 weeks, until the second overnight visit. There will also be a short blood draw visit 4 weeks after the first overnight. Participants in the study will be appropriately compensated.

Dr. Burak’s road to becoming a principal investigator for clinical trial was not easy, but it was direct. He exhaustively pursued the endpoint to see if bench laboratory discoveries have positive benefits for people. The path to successfully launching an approved clinical trial took 5 years of work toward acquiring the appropriate funding source, as well as developing the protocol and supplying the appropriate data needed to launch this investigator-initiated study. Since this is an academic study, upon completion, the data will be provided to the public so it may be useful in furthering research regarding adipose tissue-related changes in obesity, and how to reverse symptoms, while also potentially translating POA into a viable treatment option.