Elucidation of the physiological role of fatty acid elongase Elovl6 in liver and development of new strategy for the treatment of metabolic disease

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Elovl6 is a microsomal enzyme involved in the elongation of saturated and monounsaturated fatty acids with 12, 14, and 16 carbons. In this research, I generated liver-specific Elovl6 deficient mice (LKO), and aimed to elucidate the physiological role of Elovl6 in the liver and identify the lipid factor which control energy metabolismand insulin sensitivity. LKO mice reduce stearate and oleate levels, and increases palmitate and palmitoleate levels in the liver. In contrast to Elovl6^<-/->. mice, LKO mice were not protected against HFHS diet. However, high sucrose diet-feeding in LKO mice caused higher insulin sensitivity than those of flox mice. These results suggest that products of the Elovl6 reaction through de novo lipogenesis regulates hepatic insulin sensitivity, but Elovl6 inhibition in extrahepatic tissue is required to protect mice from HFHS-induced insulin resistance.