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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

BIOSIS / 2006:234207 - Revision history

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