Dear All,

I would like to cordially invite you to the habilitation lecture which will take place on the 14th of May at 3pm in the Konorski lecture hall. We will host dr Justyna Janikiewicz (Laboratory of Cell Signaling and Metabolic Disorders, Nencki Institute of Experimental Biology, PAS). Her habilitation is processed by the Scientific Council of the Nencki Institute of Experimental Biology, Polish Academy of Sciences. She will give a lecture entitled: “Not only a matter of fat: role of stearoyl-CoA desaturase 1 in adaptation and lipotoxicity of pancreatic β-cells”.

Abstract:

Obesity-associated type 2 diabetes mellitus (T2D) is an increasing global health and economic burden for which current therapeutic options are clearly inadequate. As a multisystemic disease, it has already reached pandemic proportions with adverse effects on life expectancy and shows no signs of abating. Although T2D considerably affects functioning of liver, heart and muscles due to systemic insulin resistance, it is the pancreatic β-cells failure that remains central contributor to the onset and progression of the disease. Indeed, pancreatic islets are exquisitely vulnerable to the resulting lipotoxicity and the ability of β-cells to alleviate lipotoxic stress is crucial for their functional recovery in T2D remission.
Fatty acids have pleiotropic effects on pancreatic β-cells, but the outcome of their action depends on both the degree of fatty acid desaturation and the duration of exposure. Stearoyl-CoA desaturase 1 (SCD1) is the rate-limiting enzyme that catalyses the biosynthesis of monounsaturated fatty acids from saturated substrates. In particular, SCD1 remains a key regulator of secretory capacity and function in lipid-loaded pancreatic β-cells. Therefore, I intended to unravel the molecular mechanisms underlying SCD1-regulated pancreatic islet function in both healthy and diabetic conditions - specifically in the lipotoxic milieu. Ultimately, this scientific journey has given me an understanding of the novel SCD1-mediated molecular mechanisms in pancreatic β-cells and rodent islets. In summary, these include the reduction of the autophagosome-lysosome assembly during palmitate-induced autophagy, the metabolic inability to form large lipid droplets in SCD1-activity/expression-deficient cells, which could ameliorate the effect of lipotoxicity, the characterization of the action of the SCD1 enzymatic activity product (C18:1) in the adaptation of islets to metabolic stress, describing the role of SCD1 in the preservation of β-cell mass, function and islet architecture under stressful conditions of lipid insult. Due to its high remodelling capacity and unexpected “moonlighting” functions, SCD1 has become an attractive therapeutic tool for targeting metabolic diseases. However, the beneficial effects of systemic SCD1 inhibition on adiposity may be at the expense of β-cells, which cautions against the clinical use of SCD1 inhibition in these critical cells.