A5048277209- Pancreatic function and diabetes
- Adipose Tissue and Metabolism
- Diabetes and associated disorders
- Adipokines, Inflammation, and Metabolic Diseases
- Diabetes Management and Research
- GDF15 and Related Biomarkers
- Regulation of Appetite and Obesity
- Prostate Cancer Diagnosis and Treatment
- Prostate Cancer Treatment and Research
- Nutrition and Health in Aging
- Pregnancy and preeclampsia studies
- Diet and metabolism studies
- Birth, Development, and Health
- HIV/AIDS drug development and treatment
- Metabolism, Diabetes, and Cancer
- HIV Research and Treatment
- Gestational Diabetes Research and Management
- Retinoids in leukemia and cellular processes
- Systemic Lupus Erythematosus Research
- Cannabis and Cannabinoid Research
- Chronic Kidney Disease and Diabetes
- Cardiovascular Disease and Adiposity
- HIV-related health complications and treatments
- Protease and Inhibitor Mechanisms
- Bariatric Surgery and Outcomes
Cambridge University Hospitals NHS Foundation Trust
2013-2024
University of Cambridge
2014-2024
Addenbrooke's Hospital
2010-2023
Wellcome/MRC Institute of Metabolic Science
2015-2023
Medical Research Council
2021-2023
NIHR Cambridge Biomedical Research Centre
2014-2023
National Health Service
2019-2020
William Harvey Research Institute
2016-2017
MRC Human Nutrition Research
2017
Queen Mary University of London
2017
GDF15, a hormone acting on the brainstem, has been implicated in nausea and vomiting of pregnancy, including its most severe form, hyperemesis gravidarum (HG), but full mechanistic understanding is lacking
Bone mineral density (BMD) is positively associated with body weight. This association persists even at non-load bearing sites, suggesting that a nonmechanical factor such as an adipocyte-derived hormone may modulate BMD.The objective of the study was to evaluate relationship between adiponectin, hormone, and BMD.A total 1735 nondiabetic women were recruited from large, population-based cohort (mean age, 50.0 yr). We employed linear regression methods estimate adiponectin BMD.Percentage...
Significance Hormonal factors from specialized enteroendocrine cells in the gut epithelium link availability of dietary nutrients to energy utilization and storage. Many hormones also affect behaviors such as appetite foraging, conveying for example satiating effects food consumption. Here we identify insulin-like peptide 5 (Insl5) a product colonic endocrine L-cells, show that levels were elevated calorie-restricted mice reduced after feeding. Consistent with this profile Insl5...
Developing noninvasive and accurate diagnostics that are easily manufactured, robust, reusable will provide monitoring of high-risk individuals in any clinical or point-of-care environment. We have developed a clinically relevant optical glucose nanosensor can be reused at least 400 times without compromise accuracy. The use single 6 ns laser (λ = 532 nm, 200 mJ) pulse rapidly produced off-axis Bragg diffraction gratings consisting ordered silver nanoparticles embedded within phenylboronic...
Inflammation and dysregulated immune responses play a crucial role in atherosclerosis, underlying ischaemic heart disease (IHD) acute coronary syndromes (ACSs). Immune are also major determinants of the postischaemic injury myocardial infarction. Regulatory T cells (CD4+CD25+FOXP3+; Treg) induce tolerance preserve homeostasis. Recent vivo studies suggested that low-dose interleukin-2 (IL-2) can increase Treg cell numbers. Aldesleukin is human recombinant form IL-2 has been used...
In all eutherian mammals, growth of the fetus is dependent upon a functional placenta, but whether and how latter adapts to putative fetal signals currently unknown. Here, we demonstrate, through fetal, endothelial, hematopoietic, trophoblast-specific genetic manipulations in mouse, that endothelial fetus-derived IGF2 required for continuous expansion feto-placental microvasculature late pregnancy. The angiocrine effects on placental are mediated, part, IGF2R angiopoietin-Tie2/TEK signaling....
Significance GDF15, a hormone produced by wide variety of cells undergoing different types stress, acts on receptor in the brain where it transmits signals that are perceived organism as aversive. We now report an action whereby activates endocrine stress response and increases circulating levels principal glucocorticoid (a “stress” steroid). By studying mice genetically deficient we also demonstrate GDF15 is key signal through which damage due to toxic chemicals steroid response. currently...
Abstract Missions into Deep Space are planned this decade. Yet the health consequences of exposure to microgravity and galactic cosmic radiation (GCR) over years-long missions on indispensable visceral organs such as kidney largely unexplored. We performed biomolecular (epigenomic, transcriptomic, proteomic, epiproteomic, metabolomic, metagenomic), clinical chemistry (electrolytes, endocrinology, biochemistry) morphometry (histology, 3D imaging, miRNA-ISH, tissue weights) analyses using...
Total plasma adiponectin and high-molecular weight (HMW) polymeric are strongly positively correlated with insulin sensitivity. However, we have recently reported paradoxical hyperadiponectinemia in patients severe resistance due to genetically defective receptors. This implies either that the receptor has a critical physiological role controlling production and/or clearance or constitutive dysfunction influences levels through developmental effects. The aim of current study was distinguish...
Abstract Both multi-parametric MRI (mpMRI) and the Prostate Health Index (PHI) have shown promise in predicting a positive biopsy men with suspected prostate cancer. Here we investigated value of combining both tests requiring repeat biopsy. PHI scores were measured undergoing re-biopsy an mpMRI image-guided transperineal approach (n = 279, 94 negative mpMRIs). The was assessed for ability to add all or only significant cancers (Gleason ≥7). In this study adding improved overall cancer...
High dietary sodium intake triggers increased blood pressure (BP). Animal studies show that salt loading results in dermal Na+ accumulation and lymphangiogenesis mediated by VEGF-C (vascular endothelial growth factor C), both attenuating the rise BP. Our objective was to determine whether these mechanisms function humans. We assessed skin electrolytes, BP, plasma 48 healthy participants randomized placebo (70 mmol sodium/d) slow (200 mmol/d) for 7 days. Skin K+ concentrations were measured...
Severe insulin resistance is associated with high morbidity. Identification of severely insulin-resistant patients who have genetic or acquired receptor dysfunction may aid therapeutic decision making; however, onerous diagnostic tests allied to a low frequency often preclude formal diagnosis. Our previous observation paradoxical hyperadiponectinemia in receptoropathy provides possible basis for simpler and cheaper screening test.
<ns4:p><ns4:bold>Background:</ns4:bold> Although nausea and vomiting are very common in pregnancy, their pathogenesis is poorly understood. We tested the hypothesis that circulating growth differentiation factor 15 (GDF15) concentrations early whose gene implicated hyperemesis gravidarum, associated with vomiting.</ns4:p><ns4:p> <ns4:bold>Methods: </ns4:bold>Blood samples for measurement of GDF15 human chorionic gonadotrophin (hCG) were obtained second trimester (median 15.1 (interquartile...
Abstract Following activation, T cells rapidly divide and acquire effector functions. This energetically demanding process depends upon the ability of to undergo metabolic remodeling from oxidative phosphorylation aerobic glycolysis, during which glucose is converted into lactate released extracellularly. In this article, we demonstrate that extracellular can be used dynamically assess human cell responses in vitro. Extracellular levels strongly correlated with proliferation, measuring...
The molecular heterogeneity of autoimmune and inflammatory diseases has been one the main obstacles to development safe specific therapeutic options. Here, we evaluated diagnostic clinical value a robust, inexpensive, immunoassay detecting circulating soluble form monocyte-specific surface receptor sialic acid binding Ig-like lectin 1 (sSIGLEC-1). We developed an measure sSIGLEC-1 in small volumes plasma/serum from systemic lupus erythematosus (SLE) patients (n = 75) healthy donors 504)....
Peroxisome proliferator–activated receptor (PPAR)γ is a key transcription factor facilitating fat deposition in adipose tissue through its proadipogenic and lipogenic actions. Human patients with dominant-negative mutations PPARγ display lipodystrophy extreme insulin resistance. For this reason it was completely unexpected that mice harboring an equivalent mutation (P465L) developed normal amounts of were sensitive. This finding raised important doubts about the interspecies translatability...
In this study, we define a new role for lipocalin prostaglandin D synthase (L-PGDS) in the control of metabolic fuel utilization by brown adipose tissue (BAT). We demonstrate that L-PGDS expression BAT is positively correlated with activity, upregulated peroxisome proliferator-activated receptor γ coactivator 1α or 1β and repressed receptor-interacting protein 140. Under cold-acclimated conditions, mice lacking had elevated reliance on carbohydrate to provide thermogenesis increased genes...
Summary Individuals with metabolic syndrome are at high risk of developing chronic kidney disease (CKD) through unclear pathogenic mechanisms. Obesity and diabetes known to induce glucolipotoxic effects in metabolically relevant organs. However, the role glucolipotoxicity aetiology diabetic nephropathy is debated. We generated a murine model, POKO mouse, obtained by crossing peroxisome proliferator-activated receptor gamma 2 (PPARγ2) knockout (KO) mouse into genetically obese ob/ob...
Energy dissipation through interscapular brown adipose tissue (iBAT) thermogenesis is an important contributor to adaptive energy expenditure. However, it remains unresolved how acute and chronic changes in availability are detected by the brain adjust iBAT activity maintain homeostasis. Here, we provide evidence that AGRP inhibitory tone represents energy-sparing circuit integrates environmental food cues internal signals of availability. We establish a role for nutrient-sensing mTORC1...