Research

Development of new strategies for the management and treatment of metabolic diseases by qualitative control of fatty acids

Now in the world including Japan, the prevalence of obesity and metabolic disease has grown to epidemic proportions. Therefore, understanding of the molecular basis of energy metabolism and development of the effective therapeutic approaches for preventing lifestyle-related diseases are called for immediately. 

We are working to understand the molecular mechanisms of which the nutrient signals lead to fatty acid synthesis. In this process, we identified and characterized a novel mammalian fatty acid elongase, Elovl6, which catalyzes the elongation of saturated and monounsaturated fatty acids with 12, 14, and 16 carbons (J Lipid Res. 2002). 

We have also shown that mice with targeted disruption of Elovl6 are resistant to diet-induced insulin resistance, despite their developing obesity (Nat Med. 2007, Hepatology 2020). In addition, we have reported that inhibition of Elovl6 could ameliorates the pathologies of type 2 diabetes (Diabetes 2017, Biochim Biophys Acta Mol Basis Dis. 2022), NASH (Hepatology 2012), atherosclerosis (Arterioscler Thromb Vasc Biol. 2011, J Am Heart Assoc. 2016), and cancer (Oncogenesis 2017, Leukemia 2023). These results suggest that inhibition of this elongase could be a new therapeutic approach for the treatment of diabetes, cardiovascular disease and other metabolic diseases, even with concurrent obesity.

The long-term goal of our laboratory is to understand the role of Elovl6 in health and disease, and to elucidate the molecular mechanisms by which Elovl6 regulates energy metabolism, cellular function and disease formation through modulating the quality of fatty acids. 

We also try to extend our investigations to develop new therapeutic approaches for treating lipid-related diseases such as metabolic syndrome, neurodegenerative disease and cancer based on control of fatty acid composition.