A5082631824- Pancreatic function and diabetes
- Diet, Metabolism, and Disease
- Cannabis and Cannabinoid Research
- Endoplasmic Reticulum Stress and Disease
- Muscle Physiology and Disorders
- Tissue Engineering and Regenerative Medicine
- Liver Disease Diagnosis and Treatment
- Adipose Tissue and Metabolism
- Lipid metabolism and biosynthesis
- Peroxisome Proliferator-Activated Receptors
- Diet and metabolism studies
- Muscle metabolism and nutrition
- Alcohol Consumption and Health Effects
- Dietary Effects on Health
- Neurogenetic and Muscular Disorders Research
- Protein Kinase Regulation and GTPase Signaling
- Birth, Development, and Health
- 3D Printing in Biomedical Research
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Hepatitis B Virus Studies
- Genetics and Neurodevelopmental Disorders
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Eating Disorders and Behaviors
- Cancer-related gene regulation
Novo Nordisk (United Kingdom)
2022-2024
University of Oxford
2024
University of East Anglia
2018
Karolinska Institutet
2016-2018
Skidmore College
2013-2016
Calorie restriction (CR) increases longevity and retards the development of many chronic diseases, but underlying metabolic signals are poorly understood. Increased fatty acid (FA) oxidation reduced FA synthesis have been hypothesized to be important adaptations CR. However, at steady state, must match intake plus synthesis; moreover, is low, not high, during Therefore, it clear how dynamics altered Accordingly, we measured food patterns, whole body fuel selection, endogenous synthesis, gene...
Epigenetic modifications contribute to the etiology of type 2 diabetes.We performed genome-wide methylome and transcriptome analysis in liver from severely obese men with or without diabetes non-obese discover aberrant pathways underlying development insulin resistance. Results were validated by pyrosequencing.We identified hypomethylation genes involved hepatic glycolysis resistance, concomitant increased mRNA expression protein levels. Pyrosequencing revealed CpG-site within ATF-motifs was...
Serine hydrolases are a large family of multifunctional enzymes known to influence obesity. Here, we performed activity-based protein profiling assess the functional level serine in liver biopsies from lean and obese humans order gain mechanistic insight into pathophysiology metabolic disease. We identified reduced hepatic activity carboxylesterase 2 (CES2) arylacetamide deacetylase (AADAC) human In primary hepatocytes, CES2 knockdown impaired glucose storage lipid oxidation. mice, obesity...
Objective Unrefined, complex carbohydrates and lean protein diets are used to combat obesity, although it's unknown whether more frequent meals may improve this response. The effects of consuming traditional (∼15%) versus higher (∼35%) intakes as three or six meals/day on abdominal fat, postprandial thermogenesis (TEM), cardiometabolic biomarkers in overweight individuals during 28 days energy balance (BAL) deficit (NEG), respectively were compared. Design Methods Overweight ( n = 30)...
•Genetically predicted increases in MTARC1 mRNA associate with poor liver health.•mARC1 knockdown decreases lipid accumulation primary human hepatocytes.•Hepatocyte-specific of mARC1 improves steatosis a murine NASH model. Background & AimsNon-alcoholic fatty disease (NAFLD) has prevalence ∼25% worldwide, significant public health consequences yet few effective treatments. Human genetics can help elucidate novel biology and identify targets for new therapeutics. Genetic variants...
Recent evidence suggests that lipoproteins serve as circulating reservoirs of peroxisomal proliferator activated receptor (PPAR) ligands are accessible through lipolysis. The present study was conducted to determine the biochemical basis PPAR-alpha activation by lipolysis products and their contribution function in vivo. measured bovine aortic endothelial cells following treatment with human plasma, VLDL products, or oleic acid. While plasma failed activate PPAR-alpha, acid performed...
The endocannabinoid (EC) system regulates food intake and energy metabolism. Cannabinoid receptor type 1 (CB1) antagonists show promise in the treatment of obesity its metabolic consequences. Although reduction adiposity resulting from therapy with CB1 may not account fully for concomitant improvements dyslipidemia, direct effects overactive EC signaling on plasma lipoprotein metabolism have been documented. present study used a chemical approach to evaluate increased mice by inducing acute...
Type 2 diabetes (T2D) is a chronic metabolic disorder affecting almost half billion people worldwide. Impaired function of pancreatic β-cells both hallmark T2D and an underlying factor in the pathophysiology disease. Understanding cellular mechanisms regulating appropriate insulin secretion has been long-standing interest scientific clinical communities. To identify novel genes we developed robust arrayed siRNA screen measuring basal, glucose-stimulated, augmented by EndoC-βH1 cells, human...
Endocannabinoids regulate energy balance and lipid metabolism by stimulating the cannabinoid receptor type 1 (CB1). Genetic deletion pharmacological antagonism have shown that CB1 signaling is necessary for development of obesity related metabolic disturbances. However, sufficiency endogenously produced endocannabinoids to cause hepatic accumulation insulin resistance, independent food intake, has not been demonstrated. Here, we show a single administration isopropyl dodecylfluorophosphonate...
Insulin resistance is central to the development of type 2 diabetes and related metabolic disorders. Because skeletal muscle responsible for majority whole body insulin-stimulated glucose uptake, regulation metabolism in this tissue particular importance. Although Rho GTPases many their affecters influence metabolism, there a paucity information on protein kinase N (PKN) family serine/threonine kinases. We investigated impact PKN2 insulin signaling primary human cells vitro mouse tibialis...
Yoga/Stretching (YS) and functional resistance (FR) training are popular exercise routines. A protein-pacing (PP) diet is a common dietary regimen. Thus, we assessed the effectiveness of PP alone in combination with either YS or FR to improve body composition cardiometabolic health.Twenty-seven overweight women (age = 43.2 ± 4.6 years) were randomized into 3 groups: yoga (YS, n 8) (FR, 10) (3 days/week) conjunction (50% carbohydrate, 25% protein, fat) diet-only (PP, 9) throughout 12-week...
In type II diabetes (T2DM), the heart is exposed to hyperglycaemia, hyperlipidaemia, and hyperinsulinaemia, leading insulin resistance metabolic dysfunction, culminating in diabetic cardiomyopathy (DbCM). Human-centric models of DbCM are needed provide mechanistic insights therapeutic targets a translationally relevant setting. We hypothesised that culturing human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) an (IR) media, assessing this using systems biology approach,...
Despite the well-known role of satellite cells in skeletal muscle plasticity, effect spinal cord injury on their function humans remains unknown. We determined whether affects intrinsic ability to differentiate and produce metabolically healthy myotubes. obtained vastus lateralis biopsies from eight cord-injured six able-bodied individuals. Satellite were isolated, grown differentiated vitro. Gene expression was measured by quantitative PCR. Abundance differentiation markers regulatory...
Spinal cord injury (SCI) leads to changes in the skeletal muscle below level of injury, e.g. atrophy and fiber composition change, followed by metabolic at both local systemic level. Satellite cells grown vitro have been shown reflect response type 2 diabetes, obesity, exercise neurological diseases. In this study, we assessed myogenic programming satellite from after SCI. We hypothesized that would affect ability produce a normal phenotype. were isolated vastus lateralis biopsies six able...