- Adipose Tissue and Metabolism
- Regulation of Appetite and Obesity
- Adipokines, Inflammation, and Metabolic Diseases
- Innovations in Medical Education
- Birth, Development, and Health
- Pancreatic function and diabetes
- Receptor Mechanisms and Signaling
- Health Sciences Research and Education
- Pharmacological Effects and Assays
- Peroxisome Proliferator-Activated Receptors
- Cell Adhesion Molecules Research
- Empathy and Medical Education
- Metabolism, Diabetes, and Cancer
- Diet and metabolism studies
- Atherosclerosis and Cardiovascular Diseases
- Dietary Effects on Health
- Apelin-related biomedical research
- Diabetes Treatment and Management
- Ion channel regulation and function
- Cholesterol and Lipid Metabolism
- Biochemical Analysis and Sensing Techniques
- Diabetes and associated disorders
- Healthcare professionals’ stress and burnout
- Perfectionism, Procrastination, Anxiety Studies
- Surgical Simulation and Training
Aston University
2021-2024
University of Buckingham
2010-2020
Kwame Nkrumah University of Science and Technology
2014
Laboratory for Research on Enterprise and Decisions
2013
University of Liverpool
2012
GlaxoSmithKline (United States)
2005
Hammersmith Hospital
1997-2001
British Heart Foundation
2000-2001
Swiss Red Cross
2001
Queen Mary University of London
2001
GPR41 is reportedly expressed in murine adipose tissue and mediates short chain fatty acid (SCFA)-stimulated leptin secretion by activating Galpha(i). Here, we agree with a contradictory report finding no expression of tissue. Nevertheless, the presence adenosine deaminase to minimise Galpha(i) signalling via A1 receptor, SCFA stimulated adipocytes from wild-type but not knockout mice. Expression GPR43 was reduced Acetate butyrate mesenteric adipocytes, consistent mediation response rather...
Although there is strong evidence that plasma HDL levels correlate inversely with the incidence of coronary artery disease, precise mechanism(s) for protective effect HDLs remains unclear. We recently showed inhibit endothelial cell expression cytokine-induced leukocyte adhesion molecules in vitro. Our study therefore sought to test hypothesis elevating level circulating would activation vivo.We used a porcine model inflammation previously established our laboratory, which vascular...
Context: Chemerin is a new adipokine associated with obesity and the metabolic syndrome. Gene expression levels of chemerin were elevated in adipose depots obese compared lean animals was markedly during differentiation fibroblasts into mature adipocytes. Objective: The objective study to identify factors that affect regulation potential function using genetics approach. Design, Setting, Patients, Intervention: Plasma measured subjects from San Antonio Family Heart Study, large family-based...
SCFA are produced in the gut by bacterial fermentation of undigested carbohydrates. Activation Gα i -protein-coupled receptor GPR41 β-cells and sympathetic ganglia inhibits insulin secretion increases outflow, respectively. A possible role stimulating leptin adipocytes is disputed. In present study, we investigated energy balance glucose homoeostasis knockout mice fed on a standard low-fat or high-fat diet. When diet, body fat mass was raised tolerance impaired male but not female compared...
Various foods are associated with effects against metabolic diseases such as insulin resistance and type 2 diabetes; however, their mechanisms of action mostly unclear. Fatty acids may contribute by acting precursors signalling molecules or direct activity on receptors. The medium- long-chain NEFA receptor FFA1 (free fatty acid 1, previously known GPR40) has been linked to enhancement glucose-stimulated secretion, whereas FFA4 4, GPR120) insulin-sensitising anti-inflammatory effects, both...
Despite significant advances in our understanding of the biology determining systemic energy homeostasis, treatment obesity remains a medical challenge. Activation AMP-activated protein kinase (AMPK) has been proposed as an attractive strategy for and its complications. AMPK is conserved, ubiquitously expressed, heterotrimeric serine/threonine whose short-term activation multiple beneficial metabolic effects. Whether these translate into long-term benefits complications unknown. Here, we...
The free fatty acid receptor 4 (FFA4 or GPR120) has appeared as an interesting potential target for the treatment of metabolic disorders. At present, most FFA4 ligands are carboxylic acids that assumed to mimic endogenous long-chain agonists. Here, we report preliminary structure-activity relationship studies a previously disclosed nonacidic sulfonamide agonist. Mutagenesis indicate compounds orthosteric agonists despite absence carboxylate function. preferred showed full agonist activity on...
Cannabinoid type-1 (CB1) receptor inverse agonists improve type 2 diabetes and dyslipidaemia but were discontinued due to adverse psychiatric effects. Δ(9)-Tetrahydrocannabivarin (THCV) is a neutral CB1 antagonist producing hypophagia body weight reduction in lean mice. We investigated its effects dietary-induced (DIO) genetically (ob/ob) obese mice.We performed two dose-ranging studies DIO mice; study 1: 0.3, 1, 2.5, 5 12.5 mg kg(-1), oral twice daily for 30 days 2: 0.1, 0.5, 2.5 oral, once...
Liver X receptor (LXR) nuclear receptors regulate the expression of genes involved in whole body cholesterol trafficking, including absorption, excretion, catabolism, and cellular efflux, possess both anti-inflammatory antidiabetic actions. Accordingly, LXR is considered an appealing drug target for multiple indications. Synthetic agonists demonstrated inhibition atherosclerosis progression murine genetic models; however, these other studies indicated that their major undesired side effect...
Absence of leptin is known to disrupt the development energy balance regulatory mechanisms. We investigated whether administration normally nourished rats affects in their offspring. Leptin (2 mg.kg(-1).day(-1)) was administered from day 14 pregnancy and throughout lactation. Male female offspring were fed either on chow or high-fat diets that elicited similar levels obesity sexes 6 wk 15 mo age. Treatment dams with prevented diet-induced increases rate weight gain, retroperitoneal fat pad...
Zinc-α2-glycoprotein (ZAG, also listed as AZGP1 in the MGI Database), a lipid-mobilising factor, has recently been suggested potential candidate modulation of body weight. We investigated effect increased adiposity on ZAG expression adipose tissue and liver plasma levels obese ( ob/ob ) mice compared with lean siblings. The study examined pro-inflammatory cytokine tumour necrosis factor-α (TNFα) adipocytes. Zag mRNA were significantly reduced subcutaneous (fourfold) epididymal (eightfold)...
Texture within biological specimens may reveal critical insights, while being very difficult to quantify. This is a particular problem in histological analysis. For example, cross-polar images of picrosirius stained skin exquisite structure, allowing changes the basketweave conformation healthy collagen be assessed. Existing techniques measure gross pathological changes, such as fibrosis, but are not sufficiently sensitive detect more subtle and progressive dermis, those seen ageing....
Free fatty acid receptor 1 (FFA1 or GPR40) enhances glucose-stimulated insulin secretion from pancreatic β-cells and currently attracts high interest as a new target for the treatment of type 2 diabetes. We here report discovery highly potent FFA1 agonist with favorable physicochemical pharmacokinetic properties. The compound efficiently normalizes glucose tolerance in diet-induced obese mice, an effect that is fully sustained after 29 days chronic dosing.
Increased adipocyte size and number are associated with many of the adverse effects observed in metabolic disease states. While methods to quantify such changes scientific clinical interest, manual determine both laborious intractable large scale investigations. Moreover, existing computational not fully automated. We, therefore, developed a novel automatic method provide accurate measurements cross-sectional area adipocytes histological sections, allowing rapid high-throughput...
There is relatively little direct evidence for the roles of interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) in activating endothelium vivo. The aim this study was to use vitro vivo models investigate contribution these cytokines both E-selectin expression recruitment polymorphonuclear cells (PMN) monosodium urate monohydrate (MSU) crystal-induced inflammation.MSU crystals were incubated with freshly isolated mononuclear cells, after which harvested supernatants tested their...
The capacity of vascularized xenografts to survive in the face normal levels circulating antigraft antibodies and complement has been ascribed a phenomenon referred as "endothelial cell accommodation." mechanisms whereby accommodation might occur have remained obscure. We investigated this an vitro system. A preparation polyclonal immunoglobulin, human globulin (HNG), induced change phenotype immortalized porcine endothelial cells(IPEC) suggestive accommodation; cells became resistant...
Studies in rodents and some studies humans have shown that conjugated linoleic acid (CLA), especially its trans-10, cis-12 isomer, reduces body fat content. However, but not all mice (though none rats) found CLA promotes insulin resistance. The molecular mechanisms responsible for these effects are unclear, there conflicting reports on the of peroxisomal proliferator-activated receptor-gamma (PPARgamma) activation expression. We conducted three experiments with obese over weeks, one eleven...
Over recent decades there has been a rapid rise in metabolic disorders throughout the world. Whilst lifestyle and societal habits have contributed to obesity epidemic, is now increasing evidence that early developmental environment of an infant can play pivotal role 'programming' adverse physiological phenotype later life. Clinical highlights maternal over-nutrition and/or during pregnancy presents not only effects on health, but also persistent deleterious developing child. Animal models...
The literature is unclear on whether the adipokine chemerin has pro- or anti-inflammatory properties plays any role in aetiology of type 2 diabetes obesity. To address these questions, and particular potential agonists antagonists receptor CMKLR1 treatment obesity, we studied metabolic phenotypes both male female, knockout heterozygote mice. We also investigated changes plasma levels gene mRNA content adipose tissue models obesity diabetes, response to fasting administration insulin...
We previously demonstrated in primary cultures of human subcutaneous adipocytes and a mouse model diet-induced obesity that specific microRNA-22-3p antagomirs produce significant reduction fat mass an improvement several metabolic parameters. These effects are related to the activation target genes such as KDM3A, KDM6B, PPARA, PPARGC1B SIRT1 involved lipid catabolism, thermogenesis, insulin sensitivity glucose homeostasis.We now report dedicated study exploring over course 3 months energetic...