A5047813787- Adipose Tissue and Metabolism
- Cancer, Hypoxia, and Metabolism
- Biochemical and Molecular Research
- Metabolism, Diabetes, and Cancer
- Pancreatic function and diabetes
- Diet and metabolism studies
- Enzyme function and inhibition
- Liver Disease Diagnosis and Treatment
- Regulation of Appetite and Obesity
- Adipokines, Inflammation, and Metabolic Diseases
- Diabetes Treatment and Management
- Cancer, Lipids, and Metabolism
- Diet, Metabolism, and Disease
- Mitochondrial Function and Pathology
- Birth, Development, and Health
- Muscle metabolism and nutrition
- Metabolomics and Mass Spectrometry Studies
- Diabetes and associated disorders
- Lipid metabolism and disorders
- Growth Hormone and Insulin-like Growth Factors
- Amino Acid Enzymes and Metabolism
- Peroxisome Proliferator-Activated Receptors
- Palliative Care and End-of-Life Issues
- Dietary Effects on Health
- Pancreatic and Hepatic Oncology Research
Yale University
2016-2025
Oak Ridge National Laboratory
2024
University of New Haven
2016-2023
Marie Curie
2021-2023
Yale Cancer Center
2022-2023
ORCID
2023
Royal Children's Hospital
2022
Murdoch Children's Research Institute
2022
Royal United Hospital
2021
Capital Region of Denmark
2021
Significance Chronic low-grade inflammation is a key driver of metabolic syndrome. This inflammatory response mediated by immune-cell infiltration and the expression cytokines. IL6 implicated in this response, but physiological role signaling unclear. Here, we demonstrate that source influences nature response. We report secreted myeloid cells inhibits adipose tissue macrophage (ATM) accumulation canonical mechanism, adipocytes or muscle promotes ATM noncanonical mechanism. These...
Nonalcoholic fatty liver disease (NAFLD) is a major factor in the pathogenesis of type 2 diabetes (T2D) and nonalcoholic steatohepatitis (NASH). The mitochondrial protonophore 2,4 dinitrophenol (DNP) has beneficial effects on NAFLD, insulin resistance, obesity preclinical models but too toxic for clinical use. We developed controlled-release oral formulation DNP, called CRMP (controlled-release protonophore), that produces mild hepatic uncoupling. In rat models, reduced hypertriglyceridemia,...
Pharmacologic inhibition of acetyl‐CoA carboxylase (ACC) enzymes, ACC1 and ACC2, offers an attractive therapeutic strategy for nonalcoholic fatty liver disease (NAFLD) through simultaneous acid synthesis stimulation oxidation. However, the effects ACC on hepatic mitochondrial oxidation, anaplerosis, ketogenesis in vivo are unknown. Here, we evaluated effect a liver‐directed allosteric inhibitor ACC2 (Compound 1) these parameters, as well glucose lipid metabolism, control diet‐induced rodent...
Significance Cholesterol is important for normal brain function and it believed that astrocytes produce most cholesterol. We have previously shown diabetes results in decreased cholesterol synthesis by a reduction the transcription factor sterol regulatory element-binding protein 2 (SREBP2). Using mouse model which SREBP2 has been knocked out astrocytes, we show astrocyte required development behavior. Furthermore, this shift metabolism driven increased glucose oxidation. Thus,...
Significance As it is estimated that one in three Americans will suffer from type 2 diabetes by 2050, interventions to ameliorate insulin resistance are of great interest. Adiponectin has emerged as a promising insulin-sensitizing adipokine; however, the mechanisms which adiponectin administration improves sensitivity unclear. Here, we show globular (gAcrp30) and full-length (Acrp30) reverse HFD-fed mice through reductions ectopic lipid liver muscle likely stimulation LPL activity eWAT...
Lower adipose-ChREBP and de novo lipogenesis (DNL) are associated with insulin resistance in humans. Here, we generated adipose-specific ChREBP knockout (AdChREBP KO) mice negligible sucrose-induced DNL adipose tissue (AT). Chow-fed AdChREBP KO resistant impaired action the liver, muscle, AT increased inflammation. HFD-fed also more than controls. Surprisingly, adipocytes lacking display a cell-autonomous reduction insulin-stimulated glucose transport that is mediated by Glut4 translocation...
Abstract Fibroblast growth factor-1 (FGF1) and FGF19 have been shown to improve glucose metabolism in diabetic rodents, but how this occurs is unknown. Here investigate the mechanism of action these factors, we perform intracerebroventricular (ICV) injections recombinant FGF1 or an awake rat model type 1 diabetes (T1D) measure rates whole-body lipolysis, hepatic acetyl CoA content, pyruvate carboxylase activity production. We show that ICV injection leads a ∼60% reduction production, content...
White adipose tissues (WAT) play crucial roles in maintaining whole-body energy homeostasis, and their dysfunction can contribute to hepatic insulin resistance type 2 diabetes mellitus (T2DM). However, the mechanisms underlying these alterations remain unknown. By analyzing transcriptome landscape human adipocytes based on available RNA-seq datasets from lean, obese, T2DM patients, we reveal elevated mitochondrial reactive oxygen species (ROS) pathway NF-κB signaling with altered fatty acid...
Abstract Sodium-glucose transport protein 2 (SGLT2) inhibitors are a class of anti-diabetic agents; however, concerns have been raised about their potential to induce euglycemic ketoacidosis and increase both glucose production glucagon secretion. The mechanisms behind these alterations unknown. Here we show that the SGLT2 inhibitor (SGLT2i) dapagliflozin promotes in healthy type diabetic rats setting insulinopenia through increased plasma catecholamine corticosterone concentrations...
Abstract Background Obesity confers an increased risk and accelerates the progression of multiple tumor types in rodents humans, including both breast colon cancer. Because sustained weight loss is rarely achieved, therapeutic approaches to slow or prevent obesity-associated cancer development have been limited, mechanistic insights as obesity-cancer connection lacking. Methods E0771 tumors MC38 were treated vivo mice vitro with two mechanistically different insulin-lowering agents, a...