一般口演　骨2

[O3-E-AM2-07] The role of Id4 on energy metabolism in adipose tissue and liver

〇Rongzhong Zhu Zhu¹, Yoshikazu Hayashi^1,2,3, Soi Kimura¹, Yuji Hatakeyama², Masato Hirata³, Eijiro Jimi^1,4, Tomoyo Kawakubo-Yasukochi¹ (1. OBT Res Ctr, Kyushu Univ Grad Sch Dent, 2. Div Funct Struct, Fukuoka Dent Coll, 3. Oral Med Res Ctr, Fukuoka Dent Coll, 4. Sect Mol Cell Biochem, Kyushu Univ Grad Sch Dent)

キーワード：Id4、energy metabolism、fatty acid synthesis

Id (inhibitor of DNA binding/differentiation) proteins are a group of dominant negative transcriptional regulators of basic helix-loop-helix transcription factors, consisting of Id1-Id4. Previous studies demonstrate that Id proteins are involved in the regulation of several physiological processes, including the proliferation and differentiation of many cell types, and their loss can result in various pathologies. However, the physiological functions of Id4 have yet to be fully elucidated. Recent literature indicates that Id4 is an important modulator of adipocyte differentiation. We thus sought to investigate the role of Id4 on energy metabolism in liver and white adipose tissue using Id4 deficient (Id4 KO) mice. The weight of liver and gonadal white adipose tissue in Id4 KO mice was decreased compared to those in wild-type mice. Histological analysis indicated abnormal tissue formation and little triglyceride accumulation in the white adipose tissue of Id4 KO mice. Conversely, liver specimens stained with hematoxylin and eosin showed no obvious changes between Id4 KO mice and wild-type littermates. However, RNAseq and RT-qPCR analysis revealed that genes responsible for the biosynthesis or elongation of fatty acids were significantly decreased in the liver of Id4 KO mice, compared to that of wild-type ones. In fact, our biochemical analysis demonstrated that fatty acid synthesis was significantly downregulated in the liver of Id4 KO mice, followed by a decrease in fatty acid synthesis-related proteins, such as fatty acid synthase and acetyl-CoA carboxylase 1. In addition, the amount of hepatic acetyl-CoA, which is an initiating substrate not only in fatty acid biosynthesis but also in histone acetylation, was markedly decreased in Id4 KO mice. Our subsequent analysis demonstrated that there were significant differences in the acetylation levels of core histones in wild-type versus Id4 KO mouse liver. Taken together, we suggest that Id4 is essential for fatty acid metabolism and contributes to histone modification in the liver, which regulates chromatin state and gene transcription without changing the DNA sequence. Non-member collaborator: Lo Yi-Chen (Institute of Food Science and Technology, National Taiwan Univ.), Ena Yano (OBT Res Ctr, Fac Dent Sci, Kyushu Univ.)