De novo lipogenesis in human fat and liver is linked to ChREBP-β and metabolic health

被引:247
作者
Eissing, Leah [1 ]
Scherer, Thomas [2 ]
Toedter, Klaus [1 ]
Knippschild, Uwe [3 ]
Greve, Jan Willem [4 ]
Buurman, Wim A. [5 ]
Pinnschmidt, Hans O. [6 ]
Rensen, Sander S. [5 ]
Wolf, Anna M. [3 ]
Bartelt, Alexander [1 ]
Heeren, Joerg [1 ]
Buettner, Christoph [2 ]
Scheja, Ludger [1 ]
机构
[1] Univ Med Ctr Hamburg Eppendorf, Dept Biochem & Mol Cell Biol, D-20246 Hamburg, Germany
[2] Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA
[3] Univ Ulm, Dept General & Visceral Surg, D-89081 Ulm, Germany
[4] Atrium Med Ctr Parkstad, Dept Gen Surg, NL-6401 CX Heerlen, Netherlands
[5] Maastricht Univ, Med Ctr, Dept Gen Surg, NUTRIM Sch Nutr Toxicol & Metab Res Maastricht, NL-6229 ER Maastricht, Netherlands
[6] Univ Med Ctr Hamburg Eppendorf, Dept Med Biometry & Epidemiol, D-20246 Hamburg, Germany
关键词
ENDOPLASMIC-RETICULUM STRESS; ADIPOSE-TISSUE; INSULIN-RESISTANCE; HEPATIC STEATOSIS; WEIGHT-LOSS; TRANSCRIPTION FACTOR; COA DESATURASE; ACID SYNTHESIS; GLUCOSE; OBESE;
D O I
10.1038/ncomms2537
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Clinical interest in de novo lipogenesis has been sparked by recent studies in rodents demonstrating that de novo lipogenesis specifically in white adipose tissue produces the insulin-sensitizing fatty acid palmitoleate. By contrast, hepatic lipogenesis is thought to contribute to metabolic disease. How de novo lipogenesis in white adipose tissue versus liver is altered in human obesity and insulin resistance is poorly understood. Here we show that lipogenic enzymes and the glucose transporter-4 are markedly decreased in white adipose tissue of insulin-resistant obese individuals compared with non-obese controls. By contrast, lipogenic enzymes are substantially upregulated in the liver of obese subjects. Bariatric weight loss restored de novo lipogenesis and glucose transporter-4 gene expression in white adipose tissue. Notably, lipogenic gene expression in both white adipose tissue and liver was strongly linked to the expression of carbohydrate-responsive element-binding protein-beta and to metabolic risk markers. Thus, de novo lipogenesis predicts metabolic health in humans in a tissue-specific manner and is likely regulated by glucose-dependent carbohydrate-responsive element-binding protein activation.
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页数:11
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共 60 条
[1]   Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver [J].
Abel, ED ;
Peroni, O ;
Kim, JK ;
Kim, YB ;
Boss, O ;
Hadro, E ;
Minnemann, T ;
Shulman, GI ;
Kahn, BB .
NATURE, 2001, 409 (6821) :729-733
[2]   The lipogenic transcription factor ChREBP dissociates hepatic steatosis from insulin resistance in mice and humans [J].
Benhamed, Fadila ;
Denechaud, Pierre-Damien ;
Lemoine, Maud ;
Robichon, Celine ;
Moldes, Marthe ;
Bertrand-Michel, Justine ;
Ratziu, Vlad ;
Serfaty, Lawrence ;
Housset, Chantal ;
Capeau, Jacqueline ;
Girard, Jean ;
Guillou, Herve ;
Postic, Catherine .
JOURNAL OF CLINICAL INVESTIGATION, 2012, 122 (06) :2176-2194
[3]   Early and longer term effects of gastric bypass surgery on tissue-specific insulin sensitivity and beta cell function in morbidly obese patients with and without type 2 diabetes [J].
Camastra, S. ;
Gastaldelli, A. ;
Mari, A. ;
Bonuccelli, S. ;
Scartabelli, G. ;
Frascerra, S. ;
Baldi, S. ;
Nannipieri, M. ;
Rebelos, E. ;
Anselmino, M. ;
Muscelli, E. ;
Ferrannini, E. .
DIABETOLOGIA, 2011, 54 (08) :2093-2102
[4]   Identification of a lipokine, a lipid hormone linking adipose tissue to systemic metabolism [J].
Cao, Haiming ;
Gerhold, Kristin ;
Mayers, Jared R. ;
Wiest, Michelle M. ;
Watkins, Steven M. ;
Hotamisligil, Goekhan S. .
CELL, 2008, 134 (06) :933-944
[5]   Characterizing the effects of saturated fatty acids on insulin signaling and ceramide and diacylglycerol accumulation in 3T3-L1 adipocytes and C2Cl2 myotubes [J].
Chavez, JA ;
Summers, SA .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2003, 419 (02) :101-109
[6]   A Ceramide-Centric View of Insulin Resistance [J].
Chavez, Jose A. ;
Summers, Scott A. .
CELL METABOLISM, 2012, 15 (05) :585-594
[7]   Liver-specific inhibition of ChREBP improves hepatic steatosis and insulin resistance in ob/ob mice [J].
Dentin, Renaud ;
Benhamed, Fadila ;
Hainault, Isabelle ;
Fauveau, Veronique ;
Foufelle, Fabienne ;
Dyck, Jason R. B. ;
Girard, Jean ;
Postic, Catherine .
DIABETES, 2006, 55 (08) :2159-2170
[8]   Abdominal obesity and metabolic syndrome [J].
Despres, Jean-Pierre ;
Lemieux, Isabelle .
NATURE, 2006, 444 (7121) :881-887
[9]   Increased hepatic lipogenesis but decreased expression of lipogenic gene in adipose tissue in human obesity [J].
Diraison, F ;
Dusserre, E ;
Vidal, H ;
Sothier, M ;
Beylot, M .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2002, 282 (01) :E46-E51
[10]   Nonalcoholic fatty liver disease: Improvement in liver histological analysis with weight loss [J].
Dixon, JB ;
Bhathal, PS ;
Hughes, NR ;
O'Brien, PE .
HEPATOLOGY, 2004, 39 (06) :1647-1654