title: Hepatic rRNA transcription regulates high-fat-diet-induced obesity.
abstract: Ribosome biosynthesis is a major intracellular energy-consuming process. We previously identified a nucleolar factor, nucleomethylin (NML), which regulates intracellular energy consumption by limiting rRNA transcription. Here, we show that, in livers of obese mice, the recruitment of NML to rRNA gene loci is increased to repress rRNA transcription. To clarify the relationship between obesity and rRNA transcription, we generated NML-null (NML-KO) mice. NML-KO mice show elevated rRNA level, reduced ATP concentration, and reduced lipid accumulation in the liver. Furthermore, in high-fat-diet (HFD)-fed NML-KO mice, hepatic rRNA levels are not decreased. Both weight gain and fat accumulation in HFD-fed NML-KO mice are significantly lower than those in HFD-fed wild-type mice. These findings indicate that rRNA transcriptional activation promotes hepatic energy consumption, which alters hepatic lipid metabolism. Namely, hepatic rRNA transcriptional repression by HFD feeding is essential for energy storage.
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan; Center for Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan.
authors.forename: Shohei
authors.initials: S
authors.lastname: Oie
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan; Center for Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Matsuzaki
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan; Center for Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Yokoyama
authors.affiliation: Department of Peripheral Nervous System Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Tokunaga
authors.affiliation: Graduate School of Pharmaceutical Sciences, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Waku
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan; Center for Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan.
authors.forename: Song-Iee
authors.initials: SI
authors.lastname: Han
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan; Center for Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Iwasaki
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan; Center for Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Mikogai
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan; Center for Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan.
authors.forename: Kayoko
authors.initials: K
authors.lastname: Yasuzawa-Tanaka
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan; Center for Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kishimoto
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan; Center for Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Hiyoshi
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan; Center for Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Nakajima
authors.affiliation: Department of Peripheral Nervous System Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8502, Japan; Department of Electrical Engineering and Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, 1-104 Totsukamachi, Shinjuku-ku, Tokyo 169-8050, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Araki
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Kimura
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan; Center for Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan.
authors.forename: Junn
authors.initials: J
authors.lastname: Yanagisawa
authors.affiliation: Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan; Center for Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Japan. Electronic address: akikomrym@tara.tsukuba.ac.jp.
authors.forename: Akiko
authors.initials: A
authors.lastname: Murayama
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D059305:Diet, High-Fat; D004734:Energy Metabolism; D005227:Fatty Acids / Q000096:biosynthesis; D015870:Gene Expression; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D012335:RNA, Ribosomal / Q000235:genetics / Q000378:metabolism*; D056564:Sirtuin 1 / Q000378:metabolism; D014057:Tomography, X-Ray Computed; D014158:Transcription, Genetic
chemical_list: D005227:Fatty Acids; D009687:Nuclear Proteins; D012335:RNA, Ribosomal; D000255:Adenosine Triphosphate; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1