The field of type 1 diabetes (T1D) research has several open questions that remain unanswered. These include, but are not limited to, the short-term effectiveness of current therapies, understanding how the disorder develops, and preventing or curing the disease. There is still an urgent need for safe, effective, and long-acting therapeutic agents in T1D treatment.

In collaboration with Dr. Saghatelian at Salk Institute, we identified and characterized a novel class of endogenous mammalian lipids, Fatty Acid esters of Hydroxy Fatty Acids (FAHFAs), which have potent anti-diabetic and anti-inflammatory properties (Yore MM, Syed I, et al., Cell 2014). In subsequent studies, we have demonstrated that chronic administration of one of the FAHFA family members, Palmitic Acid Hydroxy Stearic Acids (PAHSAs), in diet-induced obese mice promotes insulin sensitivity (Syed I et al., Cell Metabolism 2018).

Given these lipids' potent anti-inflammatory and insulin secretagogue properties, we investigated the role of PAHSAs in delaying the onset of and preventing T1D. Our data demonstrate that PAHSAs markedly attenuate T1D in non-obese diabetic (NOD) mice, a model of autoimmune T1D, and improve β-cell survival and function (Syed I et al., the Journal of Clinical Investigation 2019).

Our current research focuses on identifying the regulation of FAHFA family members in type 1 diabetic humans and the mechanisms by which PAHSAs/FAHFAs prevent T1D by simultaneously attenuating immune-mediated β-cell death and directly acting on β-cells to improve their survival and function. In addition, we are also studying whether FAHFA protects human-induced pluripotent stem cell-derived (hiPSCs) islet β-cells from metabolic stress and immune attack.

These studies can potentially make a significant impact on the field of T1D since the primary limitation to islet cell transplantation, now that hiPSC-derived β-cells have been developed, is immune rejection. Our ultimate goal is to develop FAHFAs as therapeutic agents to treat T1D. The pathways they engage could provide new targets for β-cell preservation and transplantation in humans with T1D.