Structural Organization and Chromosomal Assignment of the Human obese Gene

Isse, Naohi; Ogawa, Yoshihiro; Tamura, Naohisa; Masuzaki, Hiroaki; Mori, Kiyoshi; Okazaki, Taku; Satoh, Noriko; Shigemoto, Michika; Yoshimasa, Yasunao; Nishi, Shogo; Hosoda, Kiminori; Inazawa, Johji; Nakao, Kazuwa

doi:10.1074/jbc.270.46.27728

Cited by 151 publications

(74 citation statements)

References 29 publications

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“…The partial sequence of the gene identi®ed in this study (data not shown) was identical to sequences published after the termination of the present study (GeneBank accession number D63709 and D63710). 18 The coding region is contained in exons 2 and 3 which in this study have been analysed by PCR-SSCP and heteroduplex analysis.…”

Section: Resultsmentioning

confidence: 99%

Identification of two novel missense mutations in the human OB gene

et al. 1997

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OBJECTIVE: To clone the human OB gene and to investigate if mutations in the OB gene are related to juvenile onset obesity in Caucasians. DESIGN: Case-cohort study with mutational scanning of the OB gene in an obese cohort and in a population sample of young Caucasians. SUBJECTS: An obese cohort of 156 subjects with juvenile onset obesity and a population sample of 380 healthy young Caucasians. MEASUREMENTS: Various anthropometric and biochemical measures of obesity and insulin sensitivity and single strand conformation polymorphism scanning and nucleotide sequencing. RESULTS: Analysis of the coding region of the OB gene in the 536 participants revealed that one obese subject was heterozygous for a mutation at codon Phe17Leu and one normal weight subject was heterozygous for a mutation at codon Val110Met. The phenotypes of the carriers were not different from matched non-mutation carrying subjects. CONCLUSIONS: Mutations exist in the OB gene among obese as well as lean subjects although they are rare. However, it is unlikely that mutations in the coding region of the OB gene are a common cause of juvenile onset obesity among Caucasians.

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Section: Resultsmentioning

confidence: 99%

Identification of two novel missense mutations in the human OB gene

et al. 1997

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“…Differentiated adipocytes can function in an endocrine manner to secrete several cytokines, called ''adipokines,'' which include TNF-a, IL-6, leptin, adiponectin, and others (Spiegelman and Flier 1996;Matsuzawa et al 1999). These genes are found to contain binding sites for TFAP2 in their promoter (Kroeger and Abraham 1996;Isse et al 1995;Takahashi et al 2000). Given such observations, we suggest that TFAP2B plays a key role in the pathogenesis of type 2 A d ip o c y t e B r a in H e a r t K id n e y L iv e r L u n g P a n c r e a s P la c e n t a S k e le t a l m u s c le T h y m u s F e t a l B r a in F e t a l k id n e y F e t a l lu n g A d ip o c y t e B r a in H e a r t K id n e y L iv e r L u n g P la c e n t a S k e le t a l m u s c le ND P a n c r e a s Fig.…”

Section: Discussionmentioning

confidence: 99%

Genetic variations in the gene encoding TFAP2B are associated with type 2 diabetes mellitus

et al. 2005

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To search a gene(s) conferring susceptibility to type 2 diabetes mellitus, we genotyped nearly 60,000 gene-based SNPs for Japanese patients and found evidence that the gene at chromosome 6p12 encoding transcription-factor-activating protein 2b (TFAP2B) 283-292 DOI 10.1007/s10038-005-0253-9 locus: v 2 =10.9, P=0.0009; odds ratio=1.57, 95% CI 1.20-2.06, intron 1+774 (G/T); v 2 =11.6, P=0.0006; odds ratio=1.60, 95% CI 1.22-2.09, intron 1+2093 (A/C); v 2 =12.2, P=0.0004; odds ratio=1.61, 95% CI 1.23-2.11]. The association of TFAP2B with type 2 diabetes was also observed in the UK population. These results suggest that TFAP2B might be a new candidate for conferring susceptibility to type 2 diabetes and contribute to the pathogenesis of type 2 diabetes.

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“…First strand cDNA was synthesised from 0.5 mg of total RNA using random hexamers in the presence of ditiothreitol and RNAse inhibitors. Specific primers of leptin 28 (GenBank D63710), TNFa 29 (GenBank X02910) and human beta-actin 30 (GenBank M10277) were derived from the gene sequences published in GeneBank. PCR reactions were performed in a thermocycler (Progene Techne, Cambridge).…”

Section: Plasma Biochemical Analysismentioning

confidence: 99%

TNFα expression of subcutaneous adipose tissue in obese and morbid obese females: relationship to adipocyte LPL activity and leptin synthesis

et al. 2002

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INTRODUCTION:Tumor necrosis factor (TNFa) has been invoked as an adipostat. Accordingly, the adipose tissue expression of TNFa has been shown to be proportional to the degree of adiposity. The regulatory role of TNFa in obesity may be controlled by several mechanisms. These include the inhibitory effect on LPL activity, the mediation on glucose homeostasis or the effect on leptin. To assess the role of TNFa in obesity we measured adipocyte TNFa expression in 96 females with a wide range of adiposity and with or without type 2 diabetes. We analysed the relationship between TNFa expression, adipocyte LPL activity, insulin resistance and leptin in this population. RESULTS: The TNFa and leptin expression of the adipose tissue in obese and morbid obese patients were significantly higher than in controls. Obese and morbid obese patients had slightly higher levels of LPL activity, but these differences were not significant. We observed a significant relationship between adipose TNFa expression and body mass index (r ¼ 0.35, P < 0.001). TNFa expression was negatively related to LPL activity (r ¼ 7 0.28, P < 0.05) and positively related to leptin expression (r ¼ 0.35, P < 0.001). CONCLUSION: Our results indicate that obese women, even those with morbid obesity, over-express TNFa in subcutaneous adipose tissue in proportion to the magnitude of the fat depot and independently of the presence of type 2 diabetes. The TNFa system may be a homeostatic mechanism that prevents further fat deposition by regulating LPL activity and leptin production.

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Structural Organization and Chromosomal Assignment of the Human obese Gene

Cited by 151 publications

References 29 publications

Identification of two novel missense mutations in the human OB gene

Identification of two novel missense mutations in the human OB gene

Genetic variations in the gene encoding TFAP2B are associated with type 2 diabetes mellitus

TNFα expression of subcutaneous adipose tissue in obese and morbid obese females: relationship to adipocyte LPL activity and leptin synthesis

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