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The Effect of Pioglitazone on Peroxisome Proliferator-Activated Receptor-γ Target Genes Related to Lipid Storage In Vivo

Published on Jul 1, 2004in Diabetes Care15.27
· DOI :10.2337/diacare.27.7.1660
Iwona Bogacka8
Estimated H-index: 8
,
Hui Xie20
Estimated H-index: 20
+ 1 AuthorsSteven R. Smith71
Estimated H-index: 71
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Abstract
OBJECTIVE —Pioglitazone is a member of the thiazolidinediones (TZDs), insulin-sensitizing agents used to treat type 2 diabetes. The aim of this study was to define the effect of pioglitazone on the expression of genes related to carbohydrate and lipid metabolism in subcutaneous fat obtained from type 2 diabetic patients. RESEARCH DESIGN AND METHODS —Forty-eight volunteers with type 2 diabetes were divided into two groups treated for 12 weeks with placebo or pioglitazone (30 mg/day). The expression of several genes was quantified by real-time RT-PCR. RESULTS —Pioglitazone treatment increased the expression of genes involved in glycerol-3-phosphate synthesis. The mRNA expression of PEPCK-C and glycerol-3-phosphate dehydrogenase (GPDH) increased ( P P P CONCLUSIONS —Treatment with pioglitazone increased body weight, and this is associated with upregulation of some, but not all, genes previously demonstrated as “TZD responsive” in subcutaneous fat. The results suggest that TZDs might increase body weight through the upregulation of genes facilitating adipocyte lipid storage in vivo.
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  • References (40)
  • Citations (161)
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References40
Newest
A. Strawford1
Estimated H-index: 1
(University of California, Berkeley),
F. Antelo3
Estimated H-index: 3
(University of California, Berkeley)
+ 1 AuthorsMarc K. Hellerstein66
Estimated H-index: 66
(University of California, Berkeley)
The turnover of adipose tissue components (lipids and cells) and the pathways of adipose lipid deposition have been difficult to measure in humans. We apply here a 2 H 2 O long-term labeling technique for concurrent measurement of adipose-triglyceride (TG) turnover, cell (DNA) proliferation, and de novo lipogenesis (DNL). Healthy subjects drank 2 H 2 O (70 ml/day) for 5-9 wk. Subcutaneous adipose tissue aspirates were taken (gluteal, thigh, and flank depots). Deuterium incorporation into TG glyc...
Published on Dec 1, 2003in Diabetes7.20
Steven R. Smith71
Estimated H-index: 71
,
Barbara Gawronska-Kozak10
Estimated H-index: 10
+ 4 AuthorsRandall L. Mynatt29
Estimated H-index: 29
It is well recognized that the agouti/melanocortin system is an important regulator of body weight homeostasis. Given that agouti is expressed in human adipose tissue and that the ectopic expression of agouti in adipose tissue results in moderately obese mice, the link between agouti expression in human adipose tissue and obesity/type 2 diabetes was investigated. Although there was no apparent relationship between agouti mRNA levels and BMI, agouti mRNA levels were significantly elevated in subj...
Published on Aug 15, 2003in Journal of Biological Chemistry
Lea Reshef26
Estimated H-index: 26
(Case Western Reserve University),
Yael Olswang9
Estimated H-index: 9
(Case Western Reserve University)
+ 5 AuthorsRichard W. Hanson62
Estimated H-index: 62
(Case Western Reserve University)
Published on Jul 1, 2003in Nature Medicine30.64
Garry D. Tan14
Estimated H-index: 14
(University of Oxford),
Cyrille Debard23
Estimated H-index: 23
(University of Lyon)
+ 5 AuthorsFredrik Karpe67
Estimated H-index: 67
(University of Oxford)
Published on Jun 1, 2003in Diabetes7.20
Mandeep Bajaj6
Estimated H-index: 6
(University of Texas Health Science Center at San Antonio),
Swangjit Suraamornkul10
Estimated H-index: 10
+ 6 AuthorsRalph A. DeFronzo134
Estimated H-index: 134
The effect of pioglitazone on splanchnic glucose uptake (SGU), endogenous glucose production (EGP), and hepatic fat content was studied in 14 type 2 diabetic patients (age 50 ± 2 years, BMI 29.4 ± 1.1 kg/m2, HbA1c 7.8 ± 0.4%). Hepatic fat content (magnetic resonance spectroscopy) and SGU (oral glucose load- insulin clamp technique) were quantitated before and after pioglitazone (45 mg/day) therapy for 16 weeks. Subjects received a 7-h euglycemic insulin (100 mU · m−2 · min−1) clamp, and a 75-g o...
Published on May 23, 2003in Journal of Biological Chemistry
Joan Tordjman34
Estimated H-index: 34
,
Geneviève Chauvet8
Estimated H-index: 8
+ 3 AuthorsBénédicte Antoine18
Estimated H-index: 18
Abstract Thiazolidinediones are used to treat type 2 diabetes mellitus because they decrease plasma glucose, insulin, triglyceride, and fatty acid levels. Thiazolidinediones are agonists for peroxisome proliferator-activated receptor γ, a nuclear receptor that is highly expressed in fat tissue. We identify glyceroneogenesis as a target of thiazolidinediones in cultured adipocytes and fat tissues of Wistar rats. The activation of glyceroneogenesis by thiazolidinediones occurs mainly in visceral f...
Published on May 1, 2003in Biochemical and Biophysical Research Communications2.71
Haruaki Kageyama29
Estimated H-index: 29
(Showa University),
Tsutomu Hirano35
Estimated H-index: 35
(Showa University)
+ 5 AuthorsMitsuru Adachi47
Estimated H-index: 47
(Showa University)
Abstract Lipoprotein lipase (LPL), a key enzyme for triglyceride hydrolysis, is an insulin-dependent enzyme and mainly synthesized in white adipose tissue (WAT) and skeletal muscles (SM). To explore how pioglitazone, an enhancer of insulin action, affects LPL synthesis, we examined the effect of pioglitazone on LPL mRNA levels in WAT or SM of brown adipose tissue (BAT)-deficient mice, which develop insulin resistance and hypertriglyceridemia. Both LPL mRNA of WAT and SM were halved in BAT-defici...
Published on Nov 1, 2002in Diabetologia7.11
Ahmir H. Khan9
Estimated H-index: 9
(UI: University of Iowa),
Jeffrey E. Pessin75
Estimated H-index: 75
(UI: University of Iowa)
Insulin-stimulated glucose uptake in adipose tissue and striated muscle is critical for reducing post-prandial blood glucose concentrations and the dysregulation of this process is one hallmark of Type II (non-insulin-dependent) diabetes mellitus. It has been well established that the insulin-stimulated redistribution of the insulin responsive glucose transporter, GLUT-4, from intracellular storage sites to the plasma membrane depends on the production of phosphoinositide 3,4,5 trisphosphate by ...
Published on Nov 1, 2002in The FASEB Journal5.39
Elmus G. Beale26
Estimated H-index: 26
(TTU: Texas Tech University),
Robert E. Hammer90
Estimated H-index: 90
+ 1 AuthorsCharlotte Forest1
Estimated H-index: 1
(University of Paris)
Glyceroneogenesis is a generally ignored metabolic pathway that occurs in adipose tissues and liver of mammalian species. This short review highlights a series of recent discoveries showing that glyceroneogenesis is important in lipid homeostasis.—Beale, E. G., Hammer, R. E., Antoine, B., Forest, C. Glyceroneogenesis comes of age.
Published on Oct 1, 2002in Nature Medicine30.64
Hong-Ping Guan5
Estimated H-index: 5
(UPenn: University of Pennsylvania),
Yong Li3
Estimated H-index: 3
(UPenn: University of Pennsylvania)
+ 3 AuthorsMitchell A. Lazar113
Estimated H-index: 113
(UPenn: University of Pennsylvania)
Thiazolidinediones (TZDs) are effective therapies for type 2 diabetes, which has reached epidemic proportions in industrialized societies. TZD treatment reduces circulating free fatty acids (FFAs), which oppose insulin actions in skeletal muscle and other insulin target tissues. Here we report that TZDs, acting as ligands for the nuclear receptor peroxisome proliferator-activated receptor (PPAR)-y, markedly induce adipocyte glycerol kinase (GyK) gene expression. This is surprising, as standard t...
Cited By161
Newest
Published on Sep 9, 2019in European Journal of Organic Chemistry3.03
Mannem Rajeswara Reddy (Indian Institute of Technology Madras), Shanmugam Hemaiswarya14
Estimated H-index: 14
(Indian Institute of Technology Madras)
+ 2 AuthorsMukesh Doble36
Estimated H-index: 36
(Indian Institute of Technology Madras)
Published on Aug 19, 2019in Molecular Reproduction and Development2.12
Sang-Gi Jeong2
Estimated H-index: 2
(Jeju National University),
Seung-Eun Lee4
Estimated H-index: 4
(Jeju National University)
+ 6 AuthorsSe-Pill Park11
Estimated H-index: 11
(Jeju National University)
Published on Aug 1, 2018in Frontiers of Medicine in China
Ning Jiang (Peking Union Medical College), Yao Li (Peking Union Medical College)+ 1 AuthorsJing Wang (Peking Union Medical College)
The biological relevance of cytokines is known for more than 20 years. Evidence suggests that adipogenesis is one of the biological events involved in the regulation of cytokines, and pro-inflammatory cytokines (e.g., TNFα and IL-1β) inhibit adipogenesis through various pathways. This inhibitory effect can constrain the hyperplastic expandability of adipose tissues. Meanwhile, chronic low-grade inflammation is commonly observed in obese populations. In some individuals, the impaired ability of a...
Published on Apr 1, 2019in Journal of Lipid Research4.74
Mi-Jeong Lee29
Estimated H-index: 29
(ISMMS: Icahn School of Medicine at Mount Sinai),
Sukanta Jash (Heritage College of Osteopathic Medicine)+ 2 AuthorsSusan K. Fried4
Estimated H-index: 4
(ISMMS: Icahn School of Medicine at Mount Sinai)
Published on Mar 16, 2019in Molecules3.06
Paula Aranaz8
Estimated H-index: 8
,
David Navarro-Herrera2
Estimated H-index: 2
+ 7 AuthorsCarlos J. González-Navarro10
Estimated H-index: 10
Phenolic compounds might modulate adiposity. Here, we report our observation that polyphenols and phenolic acids inhibit adipogenesis in 3T3-L1 with different intensity depending on the family and the stage of differentiation. While quercetin and resveratrol inhibited lipid accumulation along the whole process of differentiation, apigenin and myricetin were active during the early and latest stages, but not intermediate, contrary to hesperidin. The activity of phenolic acids was limited to the e...
Published on Jan 7, 2019in Archives of Physiology and Biochemistry2.11
Maha M. Sabry1
Estimated H-index: 1
(Cairo University),
Amal F. Dawood (Cairo University)+ 3 AuthorsSheren Younes (Menoufia University)
AbstractObesity and atherosclerosis are inflammatory states involving variable metabolic signals. The adipokine resistin is implicated in adipose tissue dysfunction and is modulated by PPARγ. In this study, resistin and PPARγ role is investigated in the development of CVS disease. Forty-eight Adult male albino rats were divided into control, obesity and atherosclerotic groups; each group is divided into two subgroups; with and without PPARγ agonist administration for 8 weeks. To assess pathologi...
Published on Nov 1, 2018in Monatshefte Fur Chemie1.50
Radha Nandan Chaturvedi1
Estimated H-index: 1
(IGNOU: Indira Gandhi National Open University),
Krishnaiah Pendem1
Estimated H-index: 1
+ 2 AuthorsSunita Malhotra1
Estimated H-index: 1
(IGNOU: Indira Gandhi National Open University)
Published on Jun 3, 2018in International Journal of Endocrinology2.29
Alexandre Connolly (Université de Sherbrooke), Samuel Leblanc4
Estimated H-index: 4
(Université de Sherbrooke),
Jean-Patrice Baillargeon32
Estimated H-index: 32
(Université de Sherbrooke)
Polycystic ovary syndrome (PCOS) is a common and significant condition associated with hyperandrogenism, infertility, low quality of life, and metabolic comorbidities. One possible explanation of PCOS development is cellular dysfunction induced by nonesterified fatty acids (NEFAs), that is, lipotoxicity, which could explain both the hyperandrogenemia and insulin resistance that characterize women with PCOS. The literature suggests that androgen biosynthesis may be induced by overexposure of andr...
Published on May 1, 2018in Canadian Journal of Physiology and Pharmacology2.04
Samah M. Elaidy2
Estimated H-index: 2
(Suez Canal University),
Mona A. Hussain2
Estimated H-index: 2
,
Mohamed K. El-Kherbetawy2
Estimated H-index: 2
(Suez Canal University)
Targeting Peroxisome Proliferator-Activated Receptor-gamma (PPAR-γ) is an approved strategy in facing insulin resistance (IR) for the diabetes mellitus (DM)-type 2. The PPAR-γ modulators display improvements in the insulin sensitizing and adverse effects of the traditional thiazolidinediones (TZDs). Nitazoxanide (NTZ) is proposed as a PPAR-γ receptor ligand, with agonistic post-transcriptional effects. Currently, NTZ-antidiabetic activities versus pioglitazone (PIO) in a high-fat diet/streptozot...
View next paperAn Antidiabetic Thiazolidinedione Is a High Affinity Ligand for Peroxisome Proliferator-activated Receptor γ (PPARγ)