A5013261212- Regulation of Appetite and Obesity
- Adipose Tissue and Metabolism
- Metabolism, Diabetes, and Cancer
- Pancreatic function and diabetes
- Biochemical Analysis and Sensing Techniques
- Adipokines, Inflammation, and Metabolic Diseases
- Genetic Associations and Epidemiology
- Nuclear Structure and Function
- Peroxisome Proliferator-Activated Receptors
- Diabetes and associated disorders
- Diet and metabolism studies
- RNA modifications and cancer
- GDF15 and Related Biomarkers
- Lipid metabolism and biosynthesis
- Diabetes Treatment and Management
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- Nutrition and Health in Aging
- Diet, Metabolism, and Disease
- Growth Hormone and Insulin-like Growth Factors
- Nutrition, Genetics, and Disease
- Diabetes Management and Research
- Liver Disease Diagnosis and Treatment
- Genetic Syndromes and Imprinting
- Protein Kinase Regulation and GTPase Signaling
University of Cambridge
2016-2025
Wellcome/MRC Institute of Metabolic Science
2016-2025
NIHR Cambridge Biomedical Research Centre
2013-2024
Wellcome Trust
2015-2024
Medical Research Council
2014-2024
National Institute of Diabetes and Digestive and Kidney Diseases
2024
National Institutes of Health
2024
Massachusetts General Hospital
2024
University of Graz
2024
Addenbrooke's Hospital
2014-2023
Puberty, a complex biologic process involving sexual development, accelerated linear growth, and adrenal maturation, is initiated when gonadotropin-releasing hormone begins to be secreted by the hypothalamus. We conducted studies in humans mice identify genetic factors that determine onset of puberty.We used complementary approaches mice. A consanguineous family with members who lacked pubertal development (idiopathic hypogonadotropic hypogonadism) was examined for mutations candidate gene,...
Severely obese (ob/ob) mice are deficient in the adipocyte-derived hormone leptin, which acts on hypothalamus to control appetite and energy expenditure.1 The administration of leptin these corrects their obesity by reducing food intake increasing expenditure.2–4 These also have hyperinsulinemia, corticosterone excess, infertility, reversed treatment with leptin.5 In humans, serum concentrations, general, correlate positively indexes obesity.6,7 We previously described two cousins severe,...
Melanocortin 4 receptor (MC4R) deficiency is the commonest monogenic form of obesity. However, clinical spectrum and mode inheritance have not been defined, pathophysiological mechanisms leading to obesity are poorly understood, there little information regarding genotype-phenotype correlations.We determined nucleotide sequence MC4R gene in 500 probands with severe childhood Family studies were undertaken examine cosegregation identified mutations Subjects underwent metabolic endocrine...
Variants in the FTO (fat mass and obesity associated) gene are associated with increased body index humans. Here, we show by bioinformatics analysis that shares sequence motifs Fe(II)- 2-oxoglutarate–dependent oxygenases. We find recombinant murine Fto catalyzes 2OG-dependent demethylation of 3-methylthymine single-stranded DNA, concomitant production succinate, formaldehyde, carbon dioxide. Consistent a potential role nucleic acid demethylation, localizes to nucleus transfected cells....
The wide range of phenotypic abnormalities seen in the leptin-deficient ob/ob mouse and their reversibility by leptin administration provide compelling evidence for existence multiple physiological functions this hormone rodents. In contrast, information regarding roles humans is limited. Three morbidly obese children, who were congenitally deficient leptin, treated with daily subcutaneous injections recombinant human up to 4 years sustained, beneficial effects on appetite, fat mass,...
The wide range of phenotypic abnormalities seen in the leptin-deficient ob/ob mouse and their reversibility by leptin administration provide compelling evidence for existence multiple physiological functions this hormone rodents. In contrast, information regarding roles humans is limited. Three morbidly obese children, who were congenitally deficient leptin, treated with daily subcutaneous injections recombinant human up to 4 years sustained, beneficial effects on appetite, fat mass,...
Over 20 severely obese subjects in 11 independent kindreds have been reported to pathogenic heterozygous mutations the gene encoding melanocortin 4 receptor (MC4R), making this most common known monogenic cause of human obesity. To date, detailed clinical phenotype dominantly inherited disorder has not defined, and no homozygous described. We determined nucleotide sequence entire coding region MC4R 243 with severe, early-onset A novel two–base pair GT insertion codon 279 was found two...
Recent studies in murine models suggest that resistin (also called Fizz3 [1]), a novel cysteine-rich protein secreted by adipocytes, may represent the long-sought link between obesity and insulin resistance (2). Furthermore, peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists appear to inhibit expression providing possible explanation for mode of action this class sensitizers Using fluorescent real-time reverse transcriptase-polymerase chain reaction-based assay, we found...
A single family has been described in which obesity results from a mutation the leptin-receptor gene (LEPR), but prevalence of such mutations severe, early-onset not systematically examined.We sequenced LEPR 300 subjects with hyperphagia and severe obesity, including 90 probands consanguineous families, investigated extent to cosegregated affected receptor function. We evaluated metabolic, endocrine, immune function relatives.Of subjects, 8 (3%) had nonsense or missense mutations--7 were...
Studies of the fat-derived hormone leptin have provided key insights into molecular and neural components feeding behavior body weight regulation. An important challenge lies in understanding how rewarding properties food interact with, can override, physiological satiety signals promote overeating. We used functional magnetic resonance imaging to measure brain responses two human patients with congenital deficiency who were shown images before after 7 days replacement therapy. Leptin was...