BIOSIS / 2006:234207

AN

    2006:234207  BIOSIS

DN

    PREV200600228562

TI

    peroxisome proliferator-activated receptor-gamma transcriptionally
    up-regulates hormone-sensitive lipase via the involvement of
    specificity protein-1. 

AU

    Deng, Tuo; Shan, Song; Li, Ping-Ping; Shen, Zhu-Fang; Lu, Xian-Ping;
    Cheng, Jing; Ning, Zhi-Qiang [Reprint Author]

CS

    Tsing Hua Univ, Shenzhen Res Inst, Chipscreen Biosci Ltd, Shenzhen 518057,
    Peoples R China
    zqning@chipscreen.com

SO

    Endocrinology, (FEB 2006) Vol. 147, No. 2, pp. 875-884. 
    CODEN: ENDOAO. ISSN: 0013-7227. 

DT

    Article

LA

    English

ED

    Entered STN: 12 Apr 2006
    Last Updated on STN: 12 Apr 2006

AB

    Both peroxisome proliferator-activated receptor (PPAR)-gamma and
    hormone-sensitive lipase (HSL) play important roles in lipid
    metabolism and insulin sensitivity.  We demonstrate that expression of the
    HSL gene is up-regulated by PPAR gamma and PPAR gamma agonists
    (rosiglitazone and pioglitazone) in the cultured hepatic cells and
    differentiating preadipocytes.  Rosiglitazone treatment also results in
    up-regulation of the HSL gene in liver and skeleton muscle from an
    experimental obese rat model, accompanied by the decreased triglyceride
    content in these tissues.  The proximal promoter (-87 bp of the human
    HSL gene) was found to be essential for PPAR gamma-mediated
    transactivating activity.  This important promoter region contains two
    GC-boxes and binds the transcription factor specificity protein-1 (Sp1)
    but not PPAR gamma.  The Sp1-promoter binding activity can be endogenously
    enhanced by PPAR gamma and rosiglitazone, as demonstrated by analysis of
    EMSA and chromatin immunoprecipitation assay.  Mutations in the GC-box
    sequences reduce the promoter binding activity of Sp1 and the
    transactivating activity of PPAR gamma.  In addition, mithramycin A, the
    specific inhibitor for Sp1-DNA binding activity, abolishes the PPAR
    gamma-mediated up-regulation of HSL.  These results indicate that PPAR
    gamma positively regulates the HSL gene expression, and up-regulation of
    HSL by PPAR gamma requires the involvement of Sp1.  Taken together, this
    study suggests that HSL may be a newly identified PPAR gamma target
    gene, and up-regulation of HSL may be an important mechanism involved in
    action of PPAR gamma agonists in type 2 diabetes.

CC

    Cytology - Animal   02506
    Cytology - Human   02508
    Genetics - General   03502
    Genetics - Animal   03506
    Genetics - Human   03508
    Biochemistry studies - Lipids   10066
    Enzymes - General and comparative studies: coenzymes   10802
    Pathology - Therapy   12512
    Metabolism - Metabolic disorders   13020
    Nutrition - Malnutrition and obesity   13203
    Digestive system - Physiology and biochemistry   14004
    Endocrine - General   17002
    Endocrine - Pancreas   17008
    Muscle - Physiology and biochemistry   17504
    Pharmacology - Clinical pharmacology   22005
    Pharmacology - Blood and hematopoietic agents   22008
    Pharmacology - Cardiovascular system   22010
    Pharmacology - Endocrine system   22016
    Pediatrics   25000

IT

    Major Concepts
       Molecular Genetics (Biochemistry and Molecular Biophysics); Enzymology
       (Biochemistry and Molecular Biophysics); Endocrine System (Chemical
       Coordination and Homeostasis)

IT

    Parts, Structures, & Systems of Organisms
       liver: digestive system; skeletal muscle: muscular system;
       preadipocyte; hepatic cell: digestive system

IT

    Diseases
       type 2 diabetes: endocrine disease/pancreas, metabolic disease
       Diabetes Mellitus, Non-Insulin-Dependent (MeSH)

IT

    Diseases
       obesity: nutritional disease
       Obesity (MeSH)

IT

    Chemicals & Biochemicals
       triglyceride; peroxisome proliferator-activated receptor-alpha;
       hormone-sensitive lipase; pioglitazone: antidiabetic-drug;
       specificity protein 1; mithramycin A: enzyme inhibitor-drug;
       rosiglitazone: antidiabetic-drug, thrombolytic-drug, hematologic-drug,
       cardiovascular-drug, vasodilator-drug

IT

    Methods & Equipment
       immunoprecipitation: laboratory techniques, immunologic techniques;
       electrophoresis mobility shift assay [EMSA]: electrophoretic
       techniques, genetic techniques, laboratory techniques

IT

    Miscellaneous Descriptors
       lipid metabolism; insulin sensitivity

ORGN

    Classifier
       Hominidae   86215
    Super Taxa
       Primates; Mammalia; Vertebrata; Chordata; Animalia
    Organism Name
       SMMC-7721 cell line (cell_line): human hepatoma cells
       CCC-L cell line (cell_line): human fetal liver cells
    Taxa Notes
       Animals, Chordates, Humans, Mammals, Primates, Vertebrates

ORGN

    Classifier
       Muridae   86375
    Super Taxa
       Rodentia; Mammalia; Vertebrata; Chordata; Animalia
    Organism Name
       Wistar rat (common): newborn
    Taxa Notes
       Animals, Chordates, Mammals, Nonhuman Vertebrates, Nonhuman Mammals,
       Rodents, Vertebrates

RN

    9001-62-1 (hormone-sensitive lipase)
    111025-46-8 (pioglitazone)
    97666-60-9 (mithramycin A)
    122320-73-4 (rosiglitazone)

GEN

    rat HSL gene [rat hormone-sensitive lipase gene] (Muridae): up-regulation