I Sadaf Farooqi

Summary

Affiliation: University of Cambridge
Country: UK

Publications

  1. pmc Genetics of obesity
    Stephen O'Rahilly
    Department of Medicine, University of Cambridge, Addenbrooke s Hospital, UK
    Philos Trans R Soc Lond B Biol Sci 361:1095-105. 2006
  2. ncbi request reprint The severely obese patient--a genetic work-up
    I Sadaf Farooqi
    University Department of Medicine, Addenbrooke s Hospital, Cambridge, UK
    Nat Clin Pract Endocrinol Metab 2:172-7; quiz following 177. 2006
  3. ncbi request reprint Heterozygosity for a POMC-null mutation and increased obesity risk in humans
    I Sadaf Farooqi
    University Department of Clinical Biochemistry, Cambridge Institute for Medical Research, Addenbrooke s Hospital, Cambridge, CB2 2XY, UK
    Diabetes 55:2549-53. 2006
  4. ncbi request reprint Is leptin an important physiological regulator of CRP?
    I Sadaf Farooqi
    Nat Med 13:16-7; author reply 19-21. 2007
  5. ncbi request reprint Defining the neural basis of appetite and obesity: from genes to behaviour
    I Sadaf Farooqi
    University of Cambridge Metabolic Research Laboratories, Wellcome Trust MRC Institute of Metabolic Science, Addenbrooke s Hospital, Cambridge, UK
    Clin Med 14:286-9. 2014
  6. pmc Severe obesity and diabetes insipidus in a patient with PCSK1 deficiency
    Graeme R Frank
    Cohen Children s Medical Center, Division of Pediatric Endocrinology, New Hyde Park, NY 11042, USA
    Mol Genet Metab 110:191-4. 2013
  7. pmc Clinical and molecular genetic spectrum of congenital deficiency of the leptin receptor
    I Sadaf Farooqi
    Cambridge Institute for Medical Research, University Department of Clinical Biochemistry, Addenbrooke s Hospital, Cambridge, United Kingdom
    N Engl J Med 356:237-47. 2007
  8. doi request reprint Obesity genes-it's all about the parents!
    Sadaf Farooqi
    University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke s Hospital, Cambridge, UK
    Cell Metab 9:487-8. 2009
  9. doi request reprint Genetic, molecular and physiological insights into human obesity
    I Sadaf Farooqi
    Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke s Hospital, University of Cambridge, Cambridge, UK
    Eur J Clin Invest 41:451-5. 2011
  10. doi request reprint Mutations in ligands and receptors of the leptin-melanocortin pathway that lead to obesity
    I Sadaf Farooqi
    University of Cambridge Metabolic Research Laboratories, Addenbrooke s Hospital, Cambridge, UK
    Nat Clin Pract Endocrinol Metab 4:569-77. 2008

Detail Information

Publications76

  1. pmc Genetics of obesity
    Stephen O'Rahilly
    Department of Medicine, University of Cambridge, Addenbrooke s Hospital, UK
    Philos Trans R Soc Lond B Biol Sci 361:1095-105. 2006
    ..At the risk of oversimplification, it seems that from an aetiological/genetic standpoint, human obesity appears less a metabolic than a neuro-behavioural disease...
  2. ncbi request reprint The severely obese patient--a genetic work-up
    I Sadaf Farooqi
    University Department of Medicine, Addenbrooke s Hospital, Cambridge, UK
    Nat Clin Pract Endocrinol Metab 2:172-7; quiz following 177. 2006
    ..The family history was suggestive of a dominantly inherited condition, because the boy's father had been hospitalized in early childhood for the management of his obesity...
  3. ncbi request reprint Heterozygosity for a POMC-null mutation and increased obesity risk in humans
    I Sadaf Farooqi
    University Department of Clinical Biochemistry, Cambridge Institute for Medical Research, Addenbrooke s Hospital, Cambridge, CB2 2XY, UK
    Diabetes 55:2549-53. 2006
    ..191. We conclude that loss of one copy of the POMC gene predisposes to obesity in humans. Thus, genetic variants having relatively subtle effects on POMC expression and function could influence susceptibility to obesity...
  4. ncbi request reprint Is leptin an important physiological regulator of CRP?
    I Sadaf Farooqi
    Nat Med 13:16-7; author reply 19-21. 2007
  5. ncbi request reprint Defining the neural basis of appetite and obesity: from genes to behaviour
    I Sadaf Farooqi
    University of Cambridge Metabolic Research Laboratories, Wellcome Trust MRC Institute of Metabolic Science, Addenbrooke s Hospital, Cambridge, UK
    Clin Med 14:286-9. 2014
    ..These studies provide a framework for investigating patients and ultimately may guide the development of more rational, targeted therapies for genetically susceptible individuals with severe obesity...
  6. pmc Severe obesity and diabetes insipidus in a patient with PCSK1 deficiency
    Graeme R Frank
    Cohen Children s Medical Center, Division of Pediatric Endocrinology, New Hyde Park, NY 11042, USA
    Mol Genet Metab 110:191-4. 2013
    ..Although pro-vasopressin is not a known physiological substrate of PCSK1, the development of central diabetes insipidus in this proband suggests that PCSK1 deficiency can be associated with impaired osmoregulation. ..
  7. pmc Clinical and molecular genetic spectrum of congenital deficiency of the leptin receptor
    I Sadaf Farooqi
    Cambridge Institute for Medical Research, University Department of Clinical Biochemistry, Addenbrooke s Hospital, Cambridge, United Kingdom
    N Engl J Med 356:237-47. 2007
    ..A single family has been described in which obesity results from a mutation in the leptin-receptor gene (LEPR), but the prevalence of such mutations in severe, early-onset obesity has not been systematically examined...
  8. doi request reprint Obesity genes-it's all about the parents!
    Sadaf Farooqi
    University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke s Hospital, Cambridge, UK
    Cell Metab 9:487-8. 2009
    ..In this issue, Chen et al. (2009) have generated mice with brain specific deletion of either the maternal or paternal allele to trace the origin of the phenotype...
  9. doi request reprint Genetic, molecular and physiological insights into human obesity
    I Sadaf Farooqi
    Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke s Hospital, University of Cambridge, Cambridge, UK
    Eur J Clin Invest 41:451-5. 2011
    ....
  10. doi request reprint Mutations in ligands and receptors of the leptin-melanocortin pathway that lead to obesity
    I Sadaf Farooqi
    University of Cambridge Metabolic Research Laboratories, Addenbrooke s Hospital, Cambridge, UK
    Nat Clin Pract Endocrinol Metab 4:569-77. 2008
    ..The genes affected in these monogenic disorders all encode ligands and receptors of the highly conserved leptin-melanocortin pathway, which is critical for the regulation of food intake and body weight...
  11. pmc Leptin regulates striatal regions and human eating behavior
    I Sadaf Farooqi
    University Department of Medicine and Department of Clinical Biochemistry, Addenbrooke s Hospital, University of Cambridge, Cambridge CB2 2QQ, UK
    Science 317:1355. 2007
    ....
  12. doi request reprint Leptin: a pivotal regulator of human energy homeostasis
    I Sadaf Farooqi
    University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Box 289, Addenbrooke s Hospital, Cambridge CB2 0QQ, United Kingdom
    Am J Clin Nutr 89:980S-984S. 2009
    ....
  13. ncbi request reprint Genetic aspects of severe childhood obesity
    I Sadaf Farooqi
    University Department of Medicine, Addenbrooke s Hospital, Cambridge, United Kingdom
    Pediatr Endocrinol Rev 3:528-36. 2006
    ....
  14. ncbi request reprint Monogenic human obesity
    I Sadaf Farooqi
    Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke s Hospital, University of Cambridge, Cambridge, UK
    Front Horm Res 36:1-11. 2008
    ....
  15. ncbi request reprint Insights from the genetics of severe childhood obesity
    Sadaf Farooqi
    Department of Medicine, Addenbrooke s Hospital, University of Cambridge, Cambridge, UK
    Horm Res 68:5-7. 2007
    ..This knowledge has also helped to dispel the notion that obesity represents an individual defect in behaviour with no biological basis...
  16. doi request reprint Obesity due to melanocortin 4 receptor (MC4R) deficiency is associated with increased linear growth and final height, fasting hyperinsulinemia, and incompletely suppressed growth hormone secretion
    Carlos E Martinelli
    Department of Pediatrics, Hospital das Clinicas, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil
    J Clin Endocrinol Metab 96:E181-8. 2011
    ..Melanocortin receptor 4 (MC4R) deficiency is characterized by increased linear growth greater than expected for the degree of obesity...
  17. ncbi request reprint Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene
    I Sadaf Farooqi
    University Department of Medicine, Cambridge Institute for Medical Research, Addenbrooke s Hospital, Cambridge, United Kingdom
    N Engl J Med 348:1085-95. 2003
    ..However, the clinical spectrum and mode of inheritance have not been defined, pathophysiological mechanisms leading to obesity are poorly understood, and there is little information regarding genotype-phenotype correlations...
  18. ncbi request reprint Hyperphagia and early-onset obesity due to a novel homozygous missense mutation in prohormone convertase 1/3
    I Sadaf Farooqi
    University Department of Clinical Biochemistry, Addenbrooke s Hospital, Cambridge CB2 2XY, United Kingdom
    J Clin Endocrinol Metab 92:3369-73. 2007
    ..To date, only two unrelated subjects with this disorder have been reported. Research..
  19. ncbi request reprint A POMC variant implicates beta-melanocyte-stimulating hormone in the control of human energy balance
    Yung Seng Lee
    University Department of Clinical Biochemistry, Cambridge Institute for Medical Research, Addenbrooke s Hospital, Cambridge, CB2 2XY, United Kingdom
    Cell Metab 3:135-40. 2006
    ..Obese children carrying the Tyr221Cys variant were hyperphagic and showed increased linear growth, both of which are features of MC4R deficiency. These studies support a role for beta-MSH in the control of human energy homeostasis...
  20. ncbi request reprint Studies of the peptide YY and neuropeptide Y2 receptor genes in relation to human obesity and obesity-related traits
    Chiao Chien Connie Hung
    University Department of Clinical Biochemistry, Addenbrookes Hospital, Cambridge, CB2 2QQ, UK
    Diabetes 53:2461-6. 2004
    ..01). In conclusion, mutations in PYY and Y2R are not commonly found in humans with severe early-onset obesity. The relationship between common variants in Y2R and obesity-related traits deserves further exploration in other populations...
  21. ncbi request reprint A de novo mutation affecting human TrkB associated with severe obesity and developmental delay
    Giles S H Yeo
    University Department of Clinical Biochemistry, Cambridge Institute for Medical Research, Addenbrooke s Hospital, Cambridge CB2 2XY, UK
    Nat Neurosci 7:1187-9. 2004
    ..The associated impairment in memory, learning and nociception seen in the proband reflects the crucial role of TrkB in the human nervous system...
  22. pmc Large, rare chromosomal deletions associated with severe early-onset obesity
    Elena G Bochukova
    University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke s Hospital, Cambridge CB2 0QQ, UK
    Nature 463:666-70. 2010
    ..Deletion carriers exhibited hyperphagia and severe insulin resistance disproportionate for the degree of obesity. We show that copy number variation contributes significantly to the genetic architecture of human obesity...
  23. pmc Rare variants in single-minded 1 (SIM1) are associated with severe obesity
    Shwetha Ramachandrappa
    University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science, Addenbrooke s Hospital, Cambridge, United Kingdom
    J Clin Invest 123:3042-50. 2013
    ..The phenotypic similarities between patients with SIM1 deficiency and melanocortin 4 receptor (MC4R) deficiency suggest that some of the effects of SIM1 deficiency on energy homeostasis are mediated by altered melanocortin signaling. ..
  24. pmc Genome-wide SNP and CNV analysis identifies common and low-frequency variants associated with severe early-onset obesity
    Eleanor Wheeler
    Wellcome Trust Sanger Institute, Cambridge, UK
    Nat Genet 45:513-7. 2013
    ..0001). Integrative gene network pathway analysis of rare deletions indicated enrichment of genes affecting G protein-coupled receptors (GPCRs) involved in the neuronal regulation of energy homeostasis...
  25. ncbi request reprint Monogenic obesity in humans
    I Sadaf Farooqi
    Departments of Medicine and Clinical Biochemistry, Cambridge University, Addenbrooke s Hospital, Cambridge CB2 2QQ, UK
    Annu Rev Med 56:443-58. 2005
    ..Practical implications of these findings for genetic counseling, prognostication, and even therapy have already emerged...
  26. pmc Leptin regulates peripheral lipid metabolism primarily through central effects on food intake
    Xavier Prieur
    University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke s Hospital, Cambridge CB2 OQQ, United Kingdom
    Endocrinology 149:5432-9. 2008
    ..Whereas we cannot exclude direct peripheral effects of leptin on certain aspects of lipid metabolism, we were unable to detect any such effects on the parameters measured in this study...
  27. ncbi request reprint Sequence variants in the melatonin-related receptor gene (GPR50) associate with circulating triglyceride and HDL levels
    Sumit Bhattacharyya
    Department of Medicine, University of Cambridge, Cambridge, UK
    J Lipid Res 47:761-6. 2006
    ..39 mM) than wild-type subjects (1.47 mM) (P < 0.01). These findings suggest a previously unexpected role for this orphan receptor in the regulation of lipid metabolism that warrants further investigation...
  28. ncbi request reprint Does physical activity energy expenditure explain the between-individual variation in plasma leptin concentrations after adjusting for differences in body composition?
    Paul W Franks
    University of Cambridge, Department of Public Health and Primary Care, Cambridge, United Kingdom
    J Clin Endocrinol Metab 88:3258-63. 2003
    ..28, P = 0.005; women: beta = -0.23, P = 0.01; combined: beta = -0.26, P = 0.00008). These data suggest the existence in this population of an independent inverse association between PAEE and fasting plasma leptin level...
  29. pmc Functional characterization and structural modeling of obesity associated mutations in the melanocortin 4 receptor
    Karen Tan
    University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke s Hospital, Box 289, Hills Road, Cambridge CB2 2QQ, United Kingdom
    Endocrinology 150:114-25. 2009
    ..The combination of functional studies and structural modeling of naturally occurring pathogenic mutations in MC4R can provide valuable information regarding the molecular mechanism of MC4R activation and its dysfunction in human disease...
  30. ncbi request reprint Modulation of blood pressure by central melanocortinergic pathways
    Jerry R Greenfield
    University of Cambridge Metabolic Research Laboratories, Addenbrooke s Hospital, Cambridge, United Kingdom
    N Engl J Med 360:44-52. 2009
    ..Central melanocortinergic signaling is implicated in the control of energy balance and blood pressure in rodents, but there is no information regarding such an association with blood pressure in humans...
  31. ncbi request reprint High protein intake stimulates postprandial GLP1 and PYY release
    Agatha A van der Klaauw
    Department of Clinical Biochemistry, University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke s Hospital, Cambridge, UK
    Obesity (Silver Spring) 21:1602-7. 2013
    ..We studied the gut hormone response and subsequent food intake after breakfasts high in protein, carbohydrate or high in fat controlled for volume, calories and appearance...
  32. ncbi request reprint Functional characterization of naturally occurring pathogenic mutations in the human leptin receptor
    Wendy Kimber
    University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke s Hospital, Cambridge CB2 0QQ, United Kingdom
    Endocrinology 149:6043-52. 2008
    ..Naturally occurring mutations associated with human obesity are valuable tools with which to explore structure/function relationships within the LR...
  33. pmc Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency
    I Sadaf Farooqi
    University Department of Medicine, Department of Clinical Biochemistry, Addenbrooke s Hospital, Cambridge, United Kingdom
    J Clin Invest 110:1093-103. 2002
    ..The subcutaneous administration of recombinant human leptin has major and sustained beneficial effects on the multiple phenotypic abnormalities associated with congenital human leptin deficiency...
  34. ncbi request reprint Studies of the neuromedin U-2 receptor gene in human obesity: evidence for the existence of two ancestral forms of the receptor
    Sumit Bhattacharyya
    University of Cambridge, Department of Medicine, Box 232, Addenbrooke s Hospital, Hills Road, Cambridge CB2 2QQ, UK
    J Endocrinol 183:115-20. 2004
    ..Further investigation of the pharmacogenomic consequences of NMU2R variation in humans is warranted...
  35. ncbi request reprint Congenital leptin deficiency due to homozygosity for the Delta133G mutation: report of another case and evaluation of response to four years of leptin therapy
    William T Gibson
    University Department of Clinical Biochemistry, Cambridge Institute for Medical Research, Addenbrooke s Hospital, Cambridge, United Kingdom CB2 2XY
    J Clin Endocrinol Metab 89:4821-6. 2004
    ....
  36. ncbi request reprint Genetic and hereditary aspects of childhood obesity
    I Sadaf Farooqi
    University Departments of Medicine and Clinical Biochemistry, Box 232, Addenbrooke s Hospital, Cambridge CB2 2QQ, UK
    Best Pract Res Clin Endocrinol Metab 19:359-74. 2005
    ....
  37. pmc Postprandial total ghrelin suppression is modulated by melanocortin signaling in humans
    Agatha A van der Klaauw
    University of Cambridge, Metabolic Research Laboratories Box 289, Addenbrookes Hospital, Hills Road, Cambridge CB2 0QQ, United Kingdom
    J Clin Endocrinol Metab 98:E288-92. 2013
    ..Ghrelin is implicated in meal initiation because circulating levels increase before and fall after meal consumption. In rodents, ghrelin stimulates food intake via hypothalamic circuits expressing the melanocortin 4 receptor (MC4R)...
  38. ncbi request reprint Contribution of variants in the small heterodimer partner gene to birthweight, adiposity, and insulin levels: mutational analysis and association studies in multiple populations
    Chiao Chien Connie Hung
    University Departments of Medicine and Clinical Biochemistry, Cambridge Institute for Medical Research, Cambridge, U K
    Diabetes 52:1288-91. 2003
    ..03). In conclusion, although mutations in SHP are not a common cause of severe human obesity, genetic variation in the SHP locus may influence birth weight and have effects on BMI, possibly through effects on insulin secretion...
  39. ncbi request reprint Mutational analysis of the serotonin receptor 5HT2c in severe early-onset human obesity
    William T Gibson
    Department of Clinical Biochemistry and Cambridge Institute for Medical Research, Addenbrooke s Hospital, UK
    Can J Physiol Pharmacol 82:426-9. 2004
    ..9%, respectively. In conclusion, mutations in 5HT2c are unlikely to be a common cause of severe early-onset human obesity. The identification of several novel polymorphisms at this locus may aid future genetic epidemiological studies...
  40. ncbi request reprint Association of polymorphisms in GPR10, the gene encoding the prolactin-releasing peptide receptor with blood pressure, but not obesity, in a U.K. Caucasian population
    Sumit Bhattacharyya
    Department of Medicine, University of Cambridge, Addenbrooke s Hospital, Hills Road, Cambridge CB2 2QQ, U K
    Diabetes 52:1296-9. 2003
    ..The alteration in signaling properties of the receptor produced by P305L may provide a functional basis for this association...
  41. ncbi request reprint Mutations in the human melanocortin-4 receptor gene associated with severe familial obesity disrupts receptor function through multiple molecular mechanisms
    Giles S H Yeo
    Cambridge Institute for Medical Research, University of Cambridge, Addenbrooke s Hospital, Cambridge CB2 2XY, UK
    Hum Mol Genet 12:561-74. 2003
    ....
  42. ncbi request reprint Minireview: human obesity-lessons from monogenic disorders
    Stephen O'Rahilly
    University Department of Medicine, Cambridge Institute of Medical Research, Addenbrooke s Hospital, Cambridge CB2 2QQ, United Kingdom
    Endocrinology 144:3757-64. 2003
    ....
  43. pmc Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
    Elizabeth K Speliotes
    Metabolism Initiative and Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA
    Nat Genet 42:937-48. 2010
    ..Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation...
  44. ncbi request reprint Proopiomelanocortin and energy balance: insights from human and murine genetics
    Anthony P Coll
    University Departments of Medicine and Clinical Biochemistry, Cambridge Institute of Medical Research, Addenbrooke s Hospital, Cambridge, United Kingdom CB2 2QQ
    J Clin Endocrinol Metab 89:2557-62. 2004
    ....
  45. pmc Neural and behavioral effects of a novel mu opioid receptor antagonist in binge-eating obese people
    Victoria C Cambridge
    Department of Psychiatry, Behavioural and Clinical Neuroscience Institute, Cambridge Biomedical Campus, University of Cambridge, United Kingdom
    Biol Psychiatry 73:887-94. 2013
    ..Moreover, relatively few studies have used pharmacologic functional magnetic resonance imaging to probe the underlying basis of altered eating behaviors...
  46. ncbi request reprint A mutation in the thyroid hormone receptor alpha gene
    Elena Bochukova
    University of Cambridge Metabolic Research Laboratories and National Institute for Health Research Cambridge Biomedical Research Centre, Institute of Metabolic Science, Addenbrooke s Hospital, Cambridge, United Kingdom
    N Engl J Med 366:243-9. 2012
    ..Our observations are consistent with defective human TRα-mediated thyroid hormone resistance and substantiate the concept of hormone action through distinct receptor subtypes in different target tissues...
  47. pmc Hyperphagia, severe obesity, impaired cognitive function, and hyperactivity associated with functional loss of one copy of the brain-derived neurotrophic factor (BDNF) gene
    Juliette Gray
    University Department of Clinical Biochemistry, Cambridge Institute for Medical Research, Addenbrooke s Hospital, Cambridge, CB2 2XY, U K
    Diabetes 55:3366-71. 2006
    ..These findings provide direct evidence for the role of the neurotrophin BDNF in human energy homeostasis, as well as in cognitive function, memory, and behavior...
  48. pmc Genetic approaches to understanding human obesity
    Shwetha Ramachandrappa
    University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke s Hospital, Cambridge, United Kingdom
    J Clin Invest 121:2080-6. 2011
    ..We anticipate that future studies will provide the framework for the development of a more rational targeted approach to the prevention and treatment of genetically susceptible individuals...
  49. pmc Distinct modulatory effects of satiety and sibutramine on brain responses to food images in humans: a double dissociation across hypothalamus, amygdala, and ventral striatum
    Paul C Fletcher
    Department of Psychiatry, University of Cambridge, GlaxoSmithKline Clinical Unit Cambridge, Addenbrooke s Centre for Clinical Investigations, Addenbrooke s Hospital, Cambridge CB2 2QQ, United Kingdom
    J Neurosci 30:14346-55. 2010
    ..Furthermore, they support a regionally specific effect on brain function through which sibutramine exerts its clinical effect...
  50. ncbi request reprint FTO and Obesity: The Missing Link
    I Sadaf Farooqi
    University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke s Hospital, Cambridge CB2 2QQ, UK
    Cell Metab 13:7-8. 2011
    ..A recent study in Nature Genetics (Church et al., 2010) demonstrates that mice overexpressing fto exhibit a dose-dependent increase in body weight, confirming a role for FTO in the development of obesity...
  51. pmc Loss of function of the melanocortin 2 receptor accessory protein 2 is associated with mammalian obesity
    Masato Asai
    Division of Endocrinology, Department of Medicine, Boston Children s Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA
    Science 341:275-8. 2013
    ..In a study of humans with severe, early-onset obesity, we found four rare, potentially pathogenic genetic variants in MRAP2, suggesting that the gene may also contribute to body weight regulation in humans. ..
  52. ncbi request reprint Somatic mutations in ATP1A1 and CACNA1D underlie a common subtype of adrenal hypertension
    Elena A B Azizan
    Clinical Pharmacology Unit, Centre for Clinical Investigation, Addenbrooke s Hospital, University of Cambridge, Cambridge, UK
    Nat Genet 45:1055-60. 2013
    ..Many APAs with these mutations were <1 cm in diameter and had been overlooked on conventional adrenal imaging. Recognition of the distinct genotype and phenotype for this subset of APAs could facilitate diagnosis. ..
  53. ncbi request reprint A missense mutation disrupting a dibasic prohormone processing site in pro-opiomelanocortin (POMC) increases susceptibility to early-onset obesity through a novel molecular mechanism
    Benjamin G Challis
    University Department of Medicine, Addenbrooke s Hospital, Cambridge CB2 2QQ, UK
    Hum Mol Genet 11:1997-2004. 2002
    ..These results suggest that the R236G mutation may confer an inherited susceptibility to obesity through the production of an aberrant fusion protein that has the capacity to interfere with central melanocortin signalling...
  54. ncbi request reprint Leptin and the onset of puberty: insights from rodent and human genetics
    I Sadaf Farooqi
    University Department of Medicine, Addenbrooke s Hospital, Cambridge, United Kingdom
    Semin Reprod Med 20:139-44. 2002
    ..This work suggests that leptin is a metabolic gate for the onset of puberty in humans. Leptin's actions may be mediated by central pathways and by direct action on peripheral organs...
  55. pmc The hormonal control of food intake
    Anthony P Coll
    Department of Clinical Biochemistry, Cambridge Institute for Medical Research, Addenbrooke s Hospital, Cambridge CB2 2XY, United Kingdom
    Cell 129:251-62. 2007
    ..These hormones come from three major sites-fat cells, the gastrointestinal tract, and the pancreas. In this Review we provide a synthesis of recent evidence concerning the actions of these hormones on food intake...
  56. doi request reprint Oral glutamine increases circulating glucagon-like peptide 1, glucagon, and insulin concentrations in lean, obese, and type 2 diabetic subjects
    Jerry R Greenfield
    Cambridge Institute for Medical Research and Department of Clinical Biochemistry, University of Cambridge, Cambridge, UK
    Am J Clin Nutr 89:106-13. 2009
    ..We previously demonstrated that glutamine is a potent stimulus of GLP-1 secretion in vitro...
  57. ncbi request reprint Obesity and the brain: how convincing is the addiction model?
    Hisham Ziauddeen
    Department of Psychiatry, University of Cambridge, Herchel Smith Building, Addenbrooke s Hospital, Cambridge CB2 0SZ, UK
    Nat Rev Neurosci 13:279-86. 2012
    ....
  58. pmc Resistance to thyroid hormone is associated with raised energy expenditure, muscle mitochondrial uncoupling, and hyperphagia
    Catherine S Mitchell
    University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke s Hospital, Cambridge, United Kingdom
    J Clin Invest 120:1345-54. 2010
    ....
  59. ncbi request reprint Melanocortin receptors as targets in the treatment of obesity
    Daniel D Lam
    Department of Clinical Biochemistry, Addenbrooke s Hospital, University of Cambridge, Cambridge, UK
    Curr Top Med Chem 7:1085-1097. 2007
    ..However, various promising strategies are being pursued to overcome these limitations, including the synthesis of more selective and potent melanocortin analogs...
  60. ncbi request reprint Early nutrition and leptin concentrations in later life
    Atul Singhal
    MRC Childhood Nutrition Research Center, Institute of Child Health, London, United Kingdom
    Am J Clin Nutr 75:993-9. 2002
    ..Because obesity is associated with high leptin concentrations relative to fat mass, programming of leptin concentrations may be one mechanism by which early nutrition influences later obesity...
  61. pmc The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase
    Thomas Gerken
    Chemistry Research Laboratory and Oxford Centre for Integrative Systems Biology, University of Oxford, 12 Mansfield Road, Oxford, Oxon OX1 3TA, UK
    Science 318:1469-72. 2007
    ..Studies can now be directed toward determining the physiologically relevant FTO substrate and how nucleic acid methylation status is linked to increased fat mass...
  62. ncbi request reprint Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation presenting in childhood
    Diego Ize-Ludlow
    Department of Pediatrics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
    Pediatrics 120:e179-88. 2007
    ..The goal was to characterize the phenotype and potential candidate genes responsible for the syndrome of late-onset central hypoventilation with hypothalamic dysfunction...
  63. pmc Prevalence of melanocortin-4 receptor deficiency in Europeans and their age-dependent penetrance in multigenerational pedigrees
    Fanny Stutzmann
    Centre National de la Recherche Scientifique 8090, Institute of Biology, Pasteur Institute, Lille, France
    Diabetes 57:2511-8. 2008
    ..However, there is uncertainty regarding the degree of penetrance of this condition, and the putative impact of the environment on the development of obesity in MC4R mutation carriers is unknown...
  64. ncbi request reprint Obesity associated genetic variation in FTO is associated with diminished satiety
    Jane Wardle
    Health Behavior Research Centre, University College London, Gower Street, London WC1E 6BT, United Kingdom
    J Clin Endocrinol Metab 93:3640-3. 2008
    ..However, to date, it is not known whether the association between genetic variation in FTO and obesity is mediated through effects on energy intake or energy expenditure...
  65. ncbi request reprint Influence of leptin on arterial distensibility: a novel link between obesity and cardiovascular disease?
    Atul Singhal
    MRC Childhood Nutrition Research Center, Institute of Child Health, London, UK
    Circulation 106:1919-24. 2002
    ..Therefore, we tested the hypothesis that high leptin concentrations are associated with lower arterial distensibility, an index of circulatory function relevant to the atherosclerotic process...
  66. ncbi request reprint Serum ghrelin levels are inversely correlated with body mass index, age, and insulin concentrations in normal children and are markedly increased in Prader-Willi syndrome
    Andrea M Haqq
    Division of Endocrinology, Department of Pediatrics, Oregon Health and Science University, Portland, Oregon 97201, USA
    J Clin Endocrinol Metab 88:174-8. 2003
    ..Elevation of serum ghrelin levels to the degree documented in this study may play a role as an orexigenic factor driving the insatiable appetite and obesity found in PWS...
  67. pmc Small-intestinal dysfunction accompanies the complex endocrinopathy of human proprotein convertase 1 deficiency
    Robert S Jackson
    Chemical Pathology Department, East Surrey Hospital, Surrey, United Kingdom
    J Clin Invest 112:1550-60. 2003
    ....
  68. ncbi request reprint Melanocortin receptors weigh in
    Stephen O'Rahilly
    Nat Med 10:351-2. 2004
  69. ncbi request reprint Leptin predicts a worsening of the features of the metabolic syndrome independently of obesity
    Paul W Franks
    Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Phoenix, AZ 85014, USA
    Obes Res 13:1476-84. 2005
    ..Our goal was to test the hypothesis that leptin predicts the development of the features of MS independently of obesity...
  70. pmc The central melanocortin system directly controls peripheral lipid metabolism
    Ruben Nogueiras
    Obesity Research Center, Department of Psychiatry, University of Cincinnati, Cincinnati, Ohio 45237, USA
    J Clin Invest 117:3475-88. 2007
    ..We also reveal molecular underpinnings for direct control of the CNS-Mcr over lipid metabolism. These results suggest ways to design more efficient pharmacological methods for controlling adiposity...
  71. ncbi request reprint Screening the human prepro-orexin gene in a single-centre narcolepsy cohort
    Timothy G Quinnell
    Respiratory Support and Sleep Centre, Papworth Hospital, Papworth Everard, Cambridgeshire, UK
    Sleep Med 8:498-502. 2007
    ..In this study, we examined the prepro-orexin gene for mutations in a cohort of unrelated patients with narcolepsy from a national UK referral centre...
  72. ncbi request reprint Molecular genetic analysis of normosmic hypogonadotropic hypogonadism in a Turkish population: identification and detailed functional characterization of a novel mutation in the gonadotropin-releasing hormone receptor gene
    A Kemal Topaloglu
    Division of Paediatric Endocrinology and Metabolism, Cukurova University, Faculty of Medicine, Adana, Turkey
    Neuroendocrinology 84:301-8. 2006
    ..Currently known mutations account for less than 15% of cases with normosmic hypogonadotropic hypogonadism (nIHH). The objective of the study was to identify novel hereditary associations in the pathogenesis of nIHH...
  73. ncbi request reprint Melanin-concentrating hormone receptor mutations and human obesity: functional analysis
    William T Gibson
    University Department of Clinical Biochemistry, Cambridge Institute of Medical Research, Cambridge United Kingdom
    Obes Res 12:743-9. 2004
    ..Clarification of the relationship of these variants to obesity must await study in other populations and/or in genetically modified mice...
  74. ncbi request reprint A quantitative trait locus on chromosome 18q for physical activity and dietary intake in Hispanic children
    Guowen Cai
    U S Department of Agriculture Agricultural Research Service, Children s Nutrition Research Center, Baylor College of Medicine, Houston, Texas 77030, USA
    Obesity (Silver Spring) 14:1596-604. 2006
    ..Genome scans were performed to identify chromosomal regions contributing to physical activity and dietary intake traits in Hispanic children participating in the VIVA LA FAMILIA Study...
  75. ncbi request reprint Evaluation of Prader-Willi Syndrome gene MAGEL2 in severe childhood-onset obesity
    Megan A O'Neill
    Department of Medical Genetics, 8 42 Medical Science Building, University of Alberta, Edmonton, Alberta, Canada T6G 2H7
    Obes Res 13:1841-2. 2005
    ..Although no mutations likely to affect gene function were identified, we identified three variant alleles. We conclude that severe childhood-onset obesity is not commonly caused by MAGEL2 mutations...