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      Seasonal variations in photoperiod affect hepatic metabolism of medaka ( Oryzias latipes)

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          Abstract

          Organisms living in temperate regions are sensitive to seasonal variations in the environment; they are known to accumulate energy as fat in their livers during the winter when days are shorter, temperatures are lower, and food is scarce. However, the effect of variations in photoperiod alone on hepatic lipid metabolism has not been well studied. Therefore, in this study, we analyzed lipid metabolism in the liver of medaka, Oryzias latipes, while varying the length of days at constant temperature. Larger amounts of fatty acids accumulated in the liver after 14 days under short‐day conditions than under long‐day conditions. Metabolome analysis showed no accumulation of long‐chain unsaturated fatty acids, but showed a significant accumulation of long‐chain saturated fatty acids. Short‐day conditions induced a reduction in the levels of succinate, fumarate, and malate in the tricarboxylic acid cycle, decreased expression of PPARα, and decreased accumulation of acylcarnitine, which suggested inhibition of lipolysis. In addition, transparent medaka fed on a high‐fat diet under short‐day conditions exhibited greater amounts of fat accumulation and developed fatty liver. The findings of our study will be useful for creating a medaka hepatic steatosis model for future studies of hepatic steatosis‐related diseases.

          Abstract

          In this study, we analyzed lipid metabolism in the liver of medaka, Oryzias latipes, while varying the length of days at constant temperature. Larger amounts of fatty acids accumulated in the liver after 14 days under short‐day conditions than under long‐day conditions. The findings of our study will be useful for creating a medaka hepatic steatosis model for future studies of hepatic steatosis‐related diseases.

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          Most cited references30

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          An atlas of genetic influences on human blood metabolites

          Genome-wide association scans with high-throughput metabolic profiling provide unprecedented insights into how genetic variation influences metabolism and complex disease. Here we report the most comprehensive exploration of genetic loci influencing human metabolism to date, including 7,824 adult individuals from two European population studies. We report genome-wide significant associations at 145 metabolic loci and their biochemical connectivity regarding more than 400 metabolites in human blood. We extensively characterize the resulting in vivo blueprint of metabolism in human blood by integrating it with information regarding gene expression, heritability, overlap with known drug targets, previous association with complex disorders and inborn errors of metabolism. We further developed a database and web-based resources for data mining and results visualization. Our findings contribute to a greater understanding of the role of inherited variation in blood metabolic diversity, and identify potential new opportunities for pharmacologic development and disease understanding.
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            High-fat diet disrupts behavioral and molecular circadian rhythms in mice.

            The circadian clock programs daily rhythms and coordinates multiple behavioral and physiological processes, including activity, sleep, feeding, and fuel homeostasis. Recent studies indicate that genetic alteration in the core molecular clock machinery can have pronounced effects on both peripheral and central metabolic regulatory signals. Many metabolic systems also cycle and may in turn affect function of clock genes and circadian systems. However, little is known about how alterations in energy balance affect the clock. Here we show that a high-fat diet in mice leads to changes in the period of the locomotor activity rhythm and alterations in the expression and cycling of canonical circadian clock genes, nuclear receptors that regulate clock transcription factors, and clock-controlled genes involved in fuel utilization in the hypothalamus, liver, and adipose tissue. These results indicate that consumption of a high-calorie diet alters the function of the mammalian circadian clock.
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              A diet-induced animal model of non-alcoholic fatty liver disease and hepatocellular cancer

              Background & Aims The lack of a preclinical model of progressive non-alcoholic steatohepatitis (NASH) that recapitulates human disease is a barrier to therapeutic development. Methods A stable isogenic cross between C57BL/6J (B6) and 129S1/SvImJ (S129) mice were fed a high fat diet with ad libitum consumption of glucose and fructose in physiologically relevant concentrations and compared to mice fed a chow diet and also to both parent strains. Results Following initiation of the obesogenic diet, B6/129 mice developed obesity, insulin resistance, hypertriglyceridemia and increased LDL-cholesterol. They sequentially also developed steatosis (4–8 weeks), steatohepatitis (16–24 weeks), progressive fibrosis (16 weeks onwards) and spontaneous hepatocellular cancer (HCC). There was a strong concordance between the pattern of pathway activation at a transcriptomic level between humans and mice with similar histological phenotypes (FDR 0.02 for early and 0.08 for late time points). Lipogenic, inflammatory and apoptotic signaling pathways activated in human NASH were also activated in these mice. The HCC gene signature resembled the S1 and S2 human subclasses of HCC (FDR 0.01 for both). Only the B6/129 mouse but not the parent strains recapitulated all of these aspects of human NAFLD. Conclusions We here describe a diet-induced animal model of non-alcoholic fatty liver disease (DIAMOND) that recapitulates the key physiological, metabolic, histologic, transcriptomic and cell-signaling changes seen in humans with progressive NASH. Lay summary We have developed a diet-induced mouse model of non-alcoholic steatohepatitis (NASH) and hepatic cancers in a cross between two mouse strains (129S1/SvImJ and C57Bl/6J). This model mimics all the physiological, metabolic, histological, transcriptomic gene signature and clinical endpoints of human NASH and can facilitate preclinical development of therapeutic targets for NASH.

                Author and article information

                Contributors
                t-takami@yamaguchi-u.ac.jp
                Journal
                FEBS Open Bio
                FEBS Open Bio
                10.1002/(ISSN)2211-5463
                FEB4
                FEBS Open Bio
                John Wiley and Sons Inc. (Hoboken )
                2211-5463
                28 February 2021
                April 2021
                : 11
                : 4 , In the Limelight: Bioplastics ( doiID: 10.1002/feb4.v11.4 )
                : 1029-1040
                Affiliations
                [ 1 ] Department of Liver regenerative medicine Yamaguchi University School of Medicine Ube Japan
                [ 2 ] Department of Gastroenterology and Hepatology Yamaguchi University Graduate School of Medicine Ube Japan
                [ 3 ] Department of Laboratory Science Yamaguchi University Graduate School of Medicine Yamaguchi Japan
                [ 4 ] Department of Oncology and Laboratory Medicine Yamaguchi University Graduate School of Medicine Ube Japan
                [ 5 ] Yamaguchi University Health Administration Center Japan
                Author notes
                [*] [* ] Correspondence

                T. Takami, Department of Gastroenterology and Hepatology, Yamaguchi University School of Medicine, Minami Kogushi 1‐1‐1, Ube Yamaguchi 755‐8505, Japan

                Fax: 81 836 22 2240

                Tel: 81 836 22 2239

                Email: t-takami@ 123456yamaguchi-u.ac.jp

                Author information
                https://orcid.org/0000-0002-2840-8660
                Article
                FEB413095
                10.1002/2211-5463.13095
                8016123
                33475250
                f8603ed4-cf46-441f-9233-ea7081837157
                © 2021 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 13 January 2021
                : 27 April 2020
                : 19 January 2021
                Page count
                Figures: 6, Tables: 3, Pages: 12, Words: 5893
                Funding
                Funded by: Japan Society for the Promotion of Science.
                Award ID: 24659369
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                April 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.1 mode:remove_FC converted:01.04.2021

                fatty liver,medaka,metabolome,photoperiod,tricarboxylic acid cycle

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