A5016602346- Cholesterol and Lipid Metabolism
- Nutrition and Health in Aging
- Metabolism, Diabetes, and Cancer
- Histone Deacetylase Inhibitors Research
- Adipose Tissue and Metabolism
- GDF15 and Related Biomarkers
- Pancreatic function and diabetes
- Hormonal Regulation and Hypertension
- Cancer, Lipids, and Metabolism
- Peroxisome Proliferator-Activated Receptors
- Lipid metabolism and biosynthesis
- Caveolin-1 and cellular processes
- Receptor Mechanisms and Signaling
- RNA and protein synthesis mechanisms
- Liver Disease Diagnosis and Treatment
- Pharmacogenetics and Drug Metabolism
- Drug Transport and Resistance Mechanisms
- Stress Responses and Cortisol
- Diet, Metabolism, and Disease
- Diabetes Treatment and Management
- Natural Antidiabetic Agents Studies
- Adipokines, Inflammation, and Metabolic Diseases
- Body Composition Measurement Techniques
Pfizer (United States)
2017-2023
Sanford Burnham Prebys Medical Discovery Institute
2013-2020
Discovery Institute
2016-2020
Diabetes Australia
2013
Orlando Health
2013
Abstract Despite the well-documented association between insulin resistance and cardiovascular disease, key targets of relevant to development disease are not known. Here, using non-biased profiling methods, we identify enzyme flavin-containing monooxygenase 3 ( Fmo3 ) be a target insulin. FMO3 produces trimethylamine N-oxide (TMAO), which has recently been suggested promote atherosclerosis in mice humans. We show that is suppressed by vitro , increased obese/insulin resistant male...
Dysregulation of hepatic lipid and cholesterol metabolism is a significant contributor to cardiometabolic health, resulting in excessive liver accumulation ultimately non-alcoholic steatohepatitis (NASH). Therapeutic activators the AMP-Activated Protein Kinase (AMPK) have been proposed as treatment for metabolic diseases; we show that AMPK β1-biased activator PF-06409577 capable lowering systemic levels both rodent monkey preclinical models. able inhibit de novo synthesis pathways, causes...
Abstract Background Cancer cachexia is a complex metabolic disease with unmet medical need. Although many rodent models are available, none identical to the human disease. Therefore, development of new preclinical that simulate some physiological, biochemical, and clinical characteristics valuable. The HT‐1080 fibrosarcoma tumour cell line was reported induce in mice. purpose this work determine how well model could recapitulate examine its technical performance. Furthermore, efficacy...
The AMP-activated protein kinase (AMPK) is a cellular sensor of energetics and when activated in skeletal muscle during contraction can impart changes metabolism. Therapeutics that selectively activate AMPK have been developed to lower glucose levels through increased disposal rates as an approach abrogate the hyperglycemic state diabetes; however, metabolic fate following activation remains unclear. We used combination vivo evaluation homeostasis ex incubation systematically evaluate...
Abstract Urocortin 2 (UCN2) acts as a ligand for the G protein-coupled receptor corticotropin-releasing hormone (CRHR2). UCN2 has been reported to improve or worsen insulin sensitivity and glucose tolerance in vivo. Here we show that acute dosing of induces systemic resistance male mice skeletal muscle. Inversely, chronic elevation by injection with adenovirus encoding resolves metabolic complications, improving tolerance. CRHR2 recruits Gs response low concentrations UCN2, well Gi...
Several kinases are known to modulate the activity of sterol regulatory element binding proteins (SREBPs), which transcription factors that activate lipid biosynthesis. The inactive SREBP precursor forms bound endoplasmic reticulum (ER) and require cleavage activating protein (SCAP) shuttle SREBPs Golgi, where proteases cleave release active SREBPs, can then enter nucleus transcription. be down‐regulated by conditions PKA is higher such as glucagon action in liver; however, a mechanism...
e24162 Background: Platinum-based drug use in cancer treatment is restricted by dose-limiting side effects, including nausea/emesis, anorexia and weight loss that reduce patient quality of life limit adherence. Cisplatin increases GDF-15, a cytokine induces aversion, preclinical models. GDF-15 signals through the hindbrain receptor glial cell-derived neurotrophic factor alpha-like (GFRAL) cisplatin-induced was attenuated GFRAL knockout mouse. Methods: In current study, using mouse and/or...
Abstract Platinum-based chemotherapy is associated with nausea/emesis, anorexia and weight loss which reduce patient quality of life limit treatment adherence potentially leading to poor outcomes. Cisplatin increases circulating growth differentiation factor 15 (GDF-15), a cytokine that induces conditioned taste aversion, in preclinical models. GDF-15 signals through the hindbrain receptor glial cell-derived neurotrophic alpha-like (GFRAL). Cisplatin-induced anorexia/weight was attenuated...