Research Topics
Genomes and Genes
| Stephen O'RahillySummaryAffiliation: University of Cambridge Country: UK Publications
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Detail Information
Publications
Genetic factors in type 2 diabetes: the end of the beginning?Stephen O'Rahilly
University of Cambridge, Department of Clinical Biochemistry, Addenbrooke s Hospital, Cambridge CB2 2QQ, UK
Science 307:370-3. 2005....- Genetic syndromes of severe insulin resistanceRobert K Semple
Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Addenbrooke s Hospital, Cambridge, United Kingdom
Endocr Rev 32:498-514. 2011..We now review recent developments in understanding of genetic forms of severe insulin resistance and/or lipodystrophy and suggest a revised classification based on growing knowledge of the underlying pathophysiology... - The hormonal control of food intakeAnthony 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... - Human genetics illuminates the paths to metabolic diseaseStephen O'Rahilly
University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke s Hospital, Hills Road, Cambridge CB2 0QQ, UK
Nature 462:307-14. 2009.... - Human obesity as a heritable disorder of the central control of energy balanceS O'Rahilly
Department of Clinical Biochemistry, Institute of Metabolic Science, Addenbrooke s Hospital, University of Cambridge Metabolic Research Laboratories, Cambridge, UK
Int J Obes (Lond) 32:S55-61. 2008..Indeed, we hope that they may eventually lead to improved treatment for patients and, in addition, help to inculcate a more enlightened attitude to the obese with a reduction in their experience of social and economic discrimination... - Human obesity and insulin resistance: lessons from experiments of natureS O'Rahilly
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke s Hospital, Hills Road, Cambridge CB2 2QQ, UK
Biochem Soc Trans 35:33-6. 2007..Ultimately, this is a potential route to treatment of both disease types. This approach is discussed in relation to Type 2 diabetes, arising from both insufficient insulin production and insulin resistance... - C/EBP transcription factors regulate SREBP1c gene expression during adipogenesisVictoria A Payne
University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke s Hospital, Hills Road, Cambridge CB2 0QQ, UK
Biochem J 425:215-23. 2010..Moreover, the findings of the present study identify an important additional mechanism via which the C/EBP transcription factors may control a network of gene expression regulating adipogenesis, lipogenesis and insulin sensitivity... - Loss of agouti-related peptide does not significantly impact the phenotype of murine POMC deficiencyMarcus P Corander
University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Level 4, Addenbrooke s Hospital, Cambridge, UK
Endocrinology 152:1819-28. 2011..If AgRP has significant melanocortin-independent actions, these are of insufficient magnitude in vivo to impact any of the detailed phenotypes we have measured under a wide variety of conditions... - A de novo mutation affecting human TrkB associated with severe obesity and developmental delayGiles 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... - ETO/MTG8 is an inhibitor of C/EBPbeta activity and a regulator of early adipogenesisJustin J Rochford
Department of Clinical Biochemistry, University of Cambridge, Box 232, Level 4, Addenbrooke s Hospital, Hills Rd, Cambridge CB2 2QR, United Kingdom
Mol Cell Biol 24:9863-72. 2004..These findings define, for the first time, a molecular role for ETO in normal physiology as an inhibitor of C/EBPbeta and a novel regulator of early adipogenesis... - Human obesity and type 2 diabetes are associated with alterations in SREBP1 isoform expression that are reproduced ex vivo by tumor necrosis factor-alphaCiaran Sewter
Department of Clinical Biochemistry and Medicine, University of Cambridge, Addenbrooke s Hospital, Cambridge, UK
Diabetes 51:1035-41. 2002..The specific reduction in the SREBP1c isoform seen in the adipose tissue of obese and type 2 diabetic subjects can be recapitulated ex vivo by TNF-alpha, suggesting a possible mechanism for this association... - Clinical and molecular genetic spectrum of congenital deficiency of the leptin receptorI 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... - The human lipodystrophy gene BSCL2/seipin may be essential for normal adipocyte differentiationVictoria A Payne
University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke s Hospital, Cambridge, UK
Diabetes 57:2055-60. 2008..Therefore, we examined whether BSCL2 is involved in the regulation of adipocyte differentiation and the mechanism whereby pathogenic mutations in BSCL2 cause lipodystrophy... - The peroxisome proliferator-activated receptor-gamma regulates murine pyruvate carboxylase gene expression in vivo and in vitroSarawut Jitrapakdee
Cambridge Institute of Diabetes, Endocrinology, and Metabolism and the Department of Clinical Biochemistry, University of Cambridge, Addenbrooke s Hospital, Cambridge, CB2 2QR, United Kingdom
J Biol Chem 280:27466-76. 2005..Our findings identified PC as a PPARgamma-regulated gene and suggested a role for PPARgamma regulating intermediary metabolism... - Mitochondrial dysfunction in patients with primary congenital insulin resistanceAlison Sleigh
Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, United Kingdom
J Clin Invest 121:2457-61. 2011.... - Studies of the neuromedin U-2 receptor gene in human obesity: evidence for the existence of two ancestral forms of the receptorSumit 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... - Leptin deficiency unmasks the deleterious effects of impaired peroxisome proliferator-activated receptor gamma function (P465L PPARgamma) in miceSarah L Gray
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke s Hospital, Hills Road, Cambridge CB2 2QR, UK
Diabetes 55:2669-77. 2006..Thus, adipose tissue expandability is identified as an important factor for the development of insulin resistance in the context of positive energy balance... - A family with severe insulin resistance and diabetes due to a mutation in AKT2Stella George
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke s Hospital, Hills Road, Cambridge CB2 2QQ, UK
Science 304:1325-8. 2004..These findings demonstrate the central importance of AKT signaling to insulin sensitivity in humans... - Proopiomelanocortin-deficient mice are hypersensitive to the adverse metabolic effects of glucocorticoidsAnthony P Coll
University Department of Medicine, Addenbrooke s Hospital, Cambridge CB2 2QR, UK
Diabetes 54:2269-76. 2005..This may occur through a mechanism involving the suppression of AgRP by the hypoadrenal state... - TCF7L2 polymorphisms modulate proinsulin levels and beta-cell function in a British Europid populationRuth J F Loos
Medical Research Council Epidemiology Unit, Strangeways Research Laboratory, Cambridge, UK
Diabetes 56:1943-7. 2007.... - Large, rare chromosomal deletions associated with severe early-onset obesityElena 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... - Common variants near MC4R are associated with fat mass, weight and risk of obesityRuth J F Loos
MRC Epidemiology Unit, Addenbrooke s Hospital, Cambridge CB2 0QQ, UK
Nat Genet 40:768-75. 2008.... - Functional characterization and structural modeling of obesity associated mutations in the melanocortin 4 receptorKaren 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... - Sequence variants in the melatonin-related receptor gene (GPR50) associate with circulating triglyceride and HDL levelsSumit 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... - Lipodystrophy: metabolic insights from a rare disorderIsabel Huang-Doran
Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke s Hospital, University of Cambridge, Hills Road, Cambridge CB2 0QQ, UK
J Endocrinol 207:245-55. 2010.... - Leptin regulates peripheral lipid metabolism primarily through central effects on food intakeXavier 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... - Plasma adiponectin as a marker of insulin receptor dysfunction: clinical utility in severe insulin resistanceRobert K Semple
Institute of Metabolic Science, University of Cambridge, Addenbrooke s Hospital, Cambridge, UK
Diabetes Care 31:977-9. 2008..Our previous observation of paradoxical hyperadiponectinemia in insulin receptoropathy provides a possible basis for a simpler and cheaper screening test... - The Wnt antagonist Dickkopf-1 and its receptors are coordinately regulated during early human adipogenesisConstantinos Christodoulides
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke s Hospital, Hills Road, Cambridge, CB2 2QR, UK
J Cell Sci 119:2613-20. 2006..Given the public health importance of disorders of adipose mass, further knowledge of the pathways involved specifically in human adipocyte differentiation might ultimately be of clinical relevance... - A POMC variant implicates beta-melanocyte-stimulating hormone in the control of human energy balanceYung 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... - Comment on "A common genetic variant is associated with adult and childhood obesity"Ruth J F Loos
Medical Research Council Epidemiology Unit, Cambridge, UK
Science 315:187; author reply 187. 2007..However, we found no evidence of association between rs7566605 and body mass index in two large ethnically homogeneous population-based cohorts. On the contrary, an opposite tendency was observed... - The link between nutritional status and insulin sensitivity is dependent on the adipocyte-specific peroxisome proliferator-activated receptor-gamma2 isoformGema Medina-Gomez
Department of Clinical Biochemistry, University of Cambridge Addenbrooke s Hospital, Hills Road, Cambridge CB2 2QR, UK
Diabetes 54:1706-16. 2005.... - Treatment with recombinant human insulin-like growth factor (rhIGF)-I/rhIGF binding protein-3 complex improves metabolic control in subjects with severe insulin resistanceFiona M Regan
University of Cambridge, Department of Pediatrics, Cambridge, United Kingdom
J Clin Endocrinol Metab 95:2113-22. 2010..We report clinical and physiological outcomes after adjunctive therapy with rhIGF-I/rhIGFBP-3 in five subjects with SIR... - Clinical spectrum of obesity and mutations in the melanocortin 4 receptor geneI 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... - Association between physical activity and blood pressure is modified by variants in the G-protein coupled receptor 10Paul W Franks
University of Cambridge, Department of Public Health and Primary Care, Cambridge, UK
Hypertension 43:224-8. 2004..Knowledge of GPR10 genotype may define those who are least likely to benefit from physical activity. These findings may have relevance in the targeted treatment of hypertensive disease... - Studies of the peptide YY and neuropeptide Y2 receptor genes in relation to human obesity and obesity-related traitsChiao 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... - Differential lipid partitioning between adipocytes and tissue macrophages modulates macrophage lipotoxicity and M2/M1 polarization in obese miceXavier Prieur
Institute of Metabolic Science, Metabolic Research Laboratories, and Department of Clinical Biochemistry, University of Cambridge, Addenbrooke s Hospital, Cambridge, UK
Diabetes 60:797-809. 2011.... - Sequential regulation of diacylglycerol acyltransferase 2 expression by CAAT/enhancer-binding protein beta (C/EBPbeta) and C/EBPalpha during adipogenesisVictoria A Payne
Department of Clinical Biochemistry, University of Cambridge, Box 232, Level 4, Addenbrooke s Hospital, Hills Road, Cambridge CB2 2QR, United Kingdom
J Biol Chem 282:21005-14. 2007..Moreover, they further refine the complex and serial roles of the C/EBP family of transcription factors in inducing and maintaining the metabolic properties of mature adipocytes... - Functional characterization of naturally occurring pathogenic mutations in the human leptin receptorWendy 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... - 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... - Pro-opiomelanocortin modulates the thermogenic and physical activity responses to high-fat feeding and markedly influences dietary fat preferenceY C Loraine Tung
Cambridge Institute for Medical Research, Addenbrooke s Hospital, Cambridge, UK
Endocrinology 148:5331-8. 2007..This includes a major influence, readily discernible even in heterozygote animals, on the dietary preference for fat... - A prevalent variant in PPP1R3A impairs glycogen synthesis and reduces muscle glycogen content in humans and miceDavid B Savage
Department of Clinical Biochemistry and Medicine, University of Cambridge, Cambridge, United Kingdom
PLoS Med 5:e27. 2008..However, the functional implications of the mutation were not known. The objective of this study was to characterise the molecular and physiological consequences of this genetic variant... - Human frame shift mutations affecting the carboxyl terminus of perilipin increase lipolysis by failing to sequester the adipose triglyceride lipase (ATGL) coactivator AB-hydrolase-containing 5 (ABHD5)Sheetal Gandotra
Institute of Metabolic Science Metabolic Research Laboratories and the Department of Clinical Biochemistry, University of Cambridge, Addenbrooke s Hospital, Cambridge CB2 0QQ, United Kingdom
J Biol Chem 286:34998-5006. 2011..The data also suggest that pharmacological inhibition of ATGL could have therapeutic potential in patients with this rare but metabolically serious disorder... - Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profileTuomas O Kilpeläinen
Medical Research Council MRC Epidemiology Unit, Institute of Metabolic Science, Cambridge, UK
Nat Genet 43:753-60. 2011..Our findings provide new insights into adiposity and insulin resistance... - Novel leptin-regulated genes revealed by transcriptional profiling of the hypothalamic paraventricular nucleusYi Chun Loraine Tung
University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke s Hospital, Cambridge CB2 0QQ, United Kingdom
J Neurosci 28:12419-26. 2008..Thus, in addition to its effects on the expression of a broad range of neuropeptides, leptin may also exert more general influences on synaptic function in, and the bioenergetic state of, the PVN... - Hypothalamic-specific manipulation of Fto, the ortholog of the human obesity gene FTO, affects food intake in ratsYi Chun Loraine Tung
University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke s Treatment Centre, Addenbrooke s Hospital, Cambridge, United Kingdom
PLoS ONE 5:e8771. 2010..Importantly, this provide the first indication that selective alteration of FTO levels in the hypothalamus can influence food intake, a finding consistent with the reported effects of FTO alleles on appetite and food intake in man... - Peripheral administration of the N-terminal pro-opiomelanocortin fragment 1-28 to Pomc-/- mice reduces food intake and weight but does not affect adrenal growth or corticosterone productionAnthony P Coll
Departments of Clinical Biochemistry and Medicine, Cambridge Institute for Medical Research, Addenbrooke s Hospital, Cambridge CB2 2XY, UK
J Endocrinol 190:515-25. 2006..In a mouse model which lacks all endogenous POMC peptides, s.c. treatment with synthetic 1-28 POMC alone can reduce food intake and body weight, but has no impact upon adrenal growth or steroidogenesis... - Genetics of obesity in humansSadaf Farooqi
University Departments of Medicine and Clinical Biochemistry, Box 232, Addenbrooke s Hospital, Cambridge CB2 2QQ, United Kingdom
Endocr Rev 27:710-18. 2006.... - Tamoxifen-induced anorexia is associated with fatty acid synthase inhibition in the ventromedial nucleus of the hypothalamus and accumulation of malonyl-CoAMiguel Lopez
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke s Hospital, Hills Road, Cambridge CB2 2QR, U K
Diabetes 55:1327-36. 2006..The finding that TMX can modulate appetite through alterations in FAS expression and malonyl-CoA levels suggests a link between hypothalamic sex steroid receptors, fatty acid metabolism, and feeding behavior... - A comparative study of the central effects of specific proopiomelancortin (POMC)-derived melanocortin peptides on food intake and body weight in pomc null miceY C Loraine Tung
Department of Clinical Biochemistry, Cambridge Institute for Medical Research, Addenbrooke s Hospital, Cambridge CB2 2QR, United Kingdom
Endocrinology 147:5940-7. 2006..Although other melanocortins can reduce food intake in the short-term, only alpha-MSH can reduce the excess fat and lean mass found in Pomc-/- mice, mediated largely through an effect on food intake... - Distinct modulatory effects of satiety and sibutramine on brain responses to food images in humans: a double dissociation across hypothalamus, amygdala, and ventral striatumPaul 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... - Minireview: human obesity-lessons from monogenic disordersStephen O'Rahilly
University Department of Medicine, Cambridge Institute of Medical Research, Addenbrooke s Hospital, Cambridge CB2 2QQ, United Kingdom
Endocrinology 144:3757-64. 2003.... - Congenital leptin deficiency due to homozygosity for the Delta133G mutation: report of another case and evaluation of response to four years of leptin therapyWilliam 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.... - Tyrosine agonists reverse the molecular defects associated with dominant-negative mutations in human peroxisome proliferator-activated receptor gammaMaura Agostini
Department of Medicine, University of Cambridge, Addenbrooke s Hospital, United Kingdom
Endocrinology 145:1527-38. 2004..Having shown that rosiglitazone is of variable and limited efficacy in these subjects, we suggest that TAs may represent a more rational therapeutic approach... - Paradoxical elevation of high-molecular weight adiponectin in acquired extreme insulin resistance due to insulin receptor antibodiesRobert K Semple
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke s Hospital, Cambridge, UK
Diabetes 56:1712-7. 2007.... - Mutational analysis of the serotonin receptor 5HT2c in severe early-onset human obesityWilliam 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... - Role of the POZ zinc finger transcription factor FBI-1 in human and murine adipogenesisMatthias Laudes
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke s Hospital, Hills Road, Cambridge CB2 2QR, United Kingdom
J Biol Chem 279:11711-8. 2004.... - Complement abnormalities in acquired lipodystrophy revisitedDavid B Savage
Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Addenbrooke s Hospital, Hills Road, Cambridge CB2 0QQ, United Kingdom
J Clin Endocrinol Metab 94:10-6. 2009.... - Mutations in the human melanocortin-4 receptor gene associated with severe familial obesity disrupts receptor function through multiple molecular mechanismsGiles 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.... - Mutations in ligands and receptors of the leptin-melanocortin pathway that lead to obesityI 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... - Genetic defects in human pericentrin are associated with severe insulin resistance and diabetesIsabel Huang-Doran
Institute of Metabolic Science, Addenbrooke s Hospital, University of Cambridge Metabolic Research Laboratories, Cambridge, UK
Diabetes 60:925-35. 2011..We thus set out to determine the prevalence of diabetes and insulin resistance among patients with PCNT defects and examined the effects of pericentrin depletion on insulin action using 3T3-L1 adipocytes as a model system... - Lamin expression in human adipose cells in relation to anatomical site and differentiation stateChristopher J Lelliott
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke s Hospital, Hills Road, Cambridge, CB2 2QQ, United Kingdom
J Clin Endocrinol Metab 87:728-34. 2002..Nonetheless, these studies provide new information regarding the expression of lamin isoforms in normal human adipose cells, which will inform future studies of the molecular pathogenesis of FPLD... - Decreased brown adipocyte recruitment and thermogenic capacity in mice with impaired peroxisome proliferator-activated receptor (P465L PPARgamma) functionSarah L Gray
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke s Hospital, Hills Road, Cambridge CB2 2QR, United Kingdom
Endocrinology 147:5708-14. 2006.... - Leptin regulates striatal regions and human eating behaviorI 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.... - Recent advances in the genetics of severe childhood obesityI S Farooqi
University Departments of Medicine and Clinical Biochemistry, Box 157, Addenbrooke s Hospital, Cambridge CB2 2QQ, UK
Arch Dis Child 83:31-4. 2000..The discovery of these genetic defects has biological and clinical implications which are greater than the rarity of the individual diseases might suggest... - Postreceptor insulin resistance contributes to human dyslipidemia and hepatic steatosisRobert K Semple
Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Addenbrooke s Hospital, Cambridge, United Kingdom
J Clin Invest 119:315-22. 2009.... - Obesity due to melanocortin 4 receptor (MC4R) deficiency is associated with increased linear growth and final height, fasting hyperinsulinemia, and incompletely suppressed growth hormone secretionCarlos 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... - Leptin: a pivotal regulator of human energy homeostasisI 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.... - Monogenic human obesity syndromesI S Farooqi
Department of Medicine, University of Cambridge, Addenbrooke s Hospital, Cambridge, UK
Prog Brain Res 153:119-25. 2006.... - Studies of the SIM1 gene in relation to human obesity and obesity-related traitsC C C Hung
University Department of Medicine, Cambridge Institute for Medical Research, Addenbrooke s Hospital, Cambridge, UK
Int J Obes (Lond) 31:429-34. 2007..SIM1-deficient mice have a hypocellular PVN and are severely obese with increased food intake... - Uncoupling protein 3 genetic variants in human obesity: the c-55t promoter polymorphism is negatively correlated with body mass index in a UK Caucasian populationD J Halsall
University Department of Clinical Biochemistry, Addenbrooke s Hospital, Cambridge, UK
Int J Obes Relat Metab Disord 25:472-7. 2001..To investigate whether genetic variation at the UCP3 locus contributes to human obesity... - Two novel missense mutations in g protein-coupled receptor 54 in a patient with hypogonadotropic hypogonadismR K Semple
Department of Clinical Biochemistry, Addenbrooke s Hospital, Cambridge CB2 2QR, United Kingdom
J Clin Endocrinol Metab 90:1849-55. 2005..These novel mutations provide further evidence that human HH may be caused by loss-of-function mutations in GPR54... - Partial leptin deficiency and human adiposityI S Farooqi
University Departments of Medicine and Clinical Biochemistry, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK
Nature 414:34-5. 2001.... - Genetic variation in the corticotrophin-releasing factor receptors: identification of single-nucleotide polymorphisms and association studies with obesity in UK CaucasiansB G Challis
University Departments of Medicine and Clinical Biochemistry, Addenbrooke s Hospital, Cambridge, UK
Int J Obes Relat Metab Disord 28:442-6. 2004..To investigate whether genetic variation at the loci encoding the corticotropin-releasing factor receptors-1 and -2 (CRF-R1 and CRF-R2) contributes to human obesity... - Monogenic human obesity syndromesI S Farooqi
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, United Kingdom
Recent Prog Horm Res 59:409-24. 2004.... - The role of melanocortin signalling in the control of body weight: evidence from human and murine genetic modelsG S Yeo
Departments of Medicine and Clinical Biochemistry, Cambridge Institute for Medical Research, Addenbrooke s Hospital, University of Cambridge, Cambridge, UK
QJM 93:7-14. 2000..The development of pharmacological agonists acting on, or mimicking, the hypothalamic melanocortinergic pathway may provide exciting opportunities for the therapy of human obesity... - Congenital leptin deficiency is associated with severe early-onset obesity in humansC T Montague
University of Cambridge, Department of Medicine, UK
Nature 387:903-8. 1997..The severe obesity found in these congenitally leptin-deficient subjects provides the first genetic evidence that leptin is an important regulator of energy balance in humans... - Functional characterization of human NTRK2 mutations identified in patients with severe early-onset obesityJ Gray
Department of Clinical Biochemistry, Cambridge Institute for Medical Research, University of Cambridge, Addenbrooke s Hospital, Cambridge, UK
Int J Obes (Lond) 31:359-64. 2007..We have now undertaken a more detailed analysis of the in vitro functional consequences of the mutations identified: I98V, P660L, T821A and Y722C... - The CART gene and human obesity: mutational analysis and population geneticsB G Challis
University Department of Medicine, Addenbrooke s Hospital, Cambridge, UK
Diabetes 49:872-5. 2000.... - Hyperphagia, severe obesity, impaired cognitive function, and hyperactivity associated with functional loss of one copy of the brain-derived neurotrophic factor (BDNF) geneJuliette 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... - WNT10B mutations in human obesityC Christodoulides
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke s Hospital, Box 232, Cambridge, CB2 2QQ, UK
Diabetologia 49:678-84. 2006..In order to determine whether mutations in WNT10B contribute to human obesity, we screened two independent populations of obese subjects for mutations in this gene... - Genetic factors in human obesityI S Farooqi
University of Cambridge, Cambridge Institute for Medical Research and the Department of Clinical Biochemistry, Cambridge, UK
Obes Rev 8:37-40. 2007