CONTEXT: Previous studies suggest a role for fibroblast growth factor receptor 1 (FGFR1) in the regulation of energy balance. OBJECTIVE: Our objective was to investigate whether FGFR1 is an obesity gene by genetic association and functional studies. DESIGN: The study was designed to genotype common FGFR1 single-nucleotide polymorphisms (SNP) in large cohorts, confirm significant results in additional cohorts, and measure FGFR1 expression in human adipose tissue and in rodent hypothalamus. SETTING: General community and referral centers for specialized care was the setting for the study. PARTICIPANTS: We genotyped FGFR1 SNP in 2438 obese and 2115 lean adults and 985 obese and 532 population-based children. Results were confirmed in 928 obese and 2738 population-based adults and 487 obese and 441 lean children. Abdominal sc adipose tissue was investigated in 202 subjects. We also investigated diet-induced, obese fasting, and fed rats. MAIN OUTCOME MEASURES: We analyzed the association between FGFR1 SNP and obesity. In secondary analyses, we related adipose FGFR1 expression to genotype, obesity, and degree of fat cell differentiation and related hypothalamic FGFR1 to energy balance. RESULTS: FGFR1 rs7012413*T was nominally associated with obesity in all four cohorts; metaanalysis odds ratio = 1.17 (95% confidence interval = 1.10-1.25), and P = 1.8 × 10(-6), which was P = 7.0 × 10(-8) in the recessive model. rs7012413*T was associated with FGFR1 expression in adipose tissue (P < 0.0001). In this organ, but not in skeletal muscle, FGFR1 mRNA (P < 0.0001) and protein (P < 0.05) were increased in obesity. In rats, hypothalamic expression of FGFR1 declined after fasting (P < ]0.001) and increased after diet-induced obesity (P < 0.05). CONCLUSIONS: FGFR1 is a novel obesity gene that may promote obesity by influencing adipose tissue and the hypothalamic control of appetite.
CONTEXT: Previous studies suggest a role for fibroblast growth factor receptor 1 (FGFR1) in the regulation of energy balance. OBJECTIVE: Our objective was to investigate whether FGFR1 is an obesity gene by genetic association and functional studies. DESIGN: The study was designed to genotype common FGFR1 single-nucleotide polymorphisms (SNP) in large cohorts, confirm significant results in additional cohorts, and measure FGFR1 expression in human adipose tissue and in rodent hypothalamus. SETTING: General community and referral centers for specialized care was the setting for the study. PARTICIPANTS: We genotyped FGFR1 SNP in 2438 obese and 2115 lean adults and 985 obese and 532 population-based children. Results were confirmed in 928 obese and 2738 population-based adults and 487 obese and 441 lean children. Abdominal sc adipose tissue was investigated in 202 subjects. We also investigated diet-induced, obese fasting, and fed rats. MAIN OUTCOME MEASURES: We analyzed the association between FGFR1 SNP and obesity. In secondary analyses, we related adipose FGFR1 expression to genotype, obesity, and degree of fat cell differentiation and related hypothalamic FGFR1 to energy balance. RESULTS:FGFR1rs7012413*T was nominally associated with obesity in all four cohorts; metaanalysis odds ratio = 1.17 (95% confidence interval = 1.10-1.25), and P = 1.8 × 10(-6), which was P = 7.0 × 10(-8) in the recessive model. rs7012413*T was associated with FGFR1 expression in adipose tissue (P < 0.0001). In this organ, but not in skeletal muscle, FGFR1 mRNA (P < 0.0001) and protein (P < 0.05) were increased in obesity. In rats, hypothalamic expression of FGFR1 declined after fasting (P < ]0.001) and increased after diet-induced obesity (P < 0.05). CONCLUSIONS:FGFR1 is a novel obesity gene that may promote obesity by influencing adipose tissue and the hypothalamic control of appetite.
Authors: Hong Jiao; Peter Arner; Paul Gerdhem; Rona J Strawbridge; Erik Näslund; Anders Thorell; Anders Hamsten; Juha Kere; Ingrid Dahlman Journal: Eur J Hum Genet Date: 2014-11-19 Impact factor: 4.246
Authors: Arthur B Jenkins; Marijka Batterham; Dorit Samocha-Bonet; Katherine Tonks; Jerry R Greenfield; Lesley V Campbell Journal: PLoS One Date: 2013-08-07 Impact factor: 3.240
Authors: Christopher J Lelliott; Andrea Ahnmark; Therese Admyre; Ingela Ahlstedt; Lorraine Irving; Feenagh Keyes; Laurel Patterson; Michael B Mumphrey; Mikael Bjursell; Tracy Gorman; Mohammad Bohlooly-Y; Andrew Buchanan; Paula Harrison; Tristan Vaughan; Hans-Rudolf Berthoud; Daniel Lindén Journal: PLoS One Date: 2014-11-26 Impact factor: 3.240
Authors: C George Priya Doss; B Rajith; Nimisha Garwasis; Pretty Raju Mathew; Anand Solomon Raju; K Apoorva; Denise William; N R Sadhana; Tanwar Himani; I P Dike Journal: Appl Transl Genom Date: 2012-10-03
Authors: Vanlata Patel; Raghu Adya; Jing Chen; Manjunath Ramanjaneya; Muhammad F Bari; Sunil K Bhudia; Edward W Hillhouse; Bee K Tan; Harpal S Randeva Journal: PLoS One Date: 2014-02-03 Impact factor: 3.240