A5037095521- Regulation of Appetite and Obesity
- Adipose Tissue and Metabolism
- Pancreatic function and diabetes
- Metabolism, Diabetes, and Cancer
- Biochemical Analysis and Sensing Techniques
- Adipokines, Inflammation, and Metabolic Diseases
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Diet, Metabolism, and Disease
- Diabetes Treatment and Management
- Fibroblast Growth Factor Research
- Diet and metabolism studies
- Exercise and Physiological Responses
- Epigenetics and DNA Methylation
- Diabetes and associated disorders
- Liver Disease Diagnosis and Treatment
- Kruppel-like factors research
- Retinoids in leukemia and cellular processes
- Biochemical effects in animals
- Endoplasmic Reticulum Stress and Disease
- Receptor Mechanisms and Signaling
- Sirtuins and Resveratrol in Medicine
- Metabolism and Genetic Disorders
- Mitochondrial Function and Pathology
- FOXO transcription factor regulation
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
The University of Texas Southwestern Medical Center
2013-2024
Southwestern Medical Center
2010-2021
Advanced Imaging Research (United States)
2012-2019
Imaging Center
2014-2017
Howard Hughes Medical Institute
2015
Vanderbilt University
2005-2012
National Institutes of Health
2009
Averett University
2007
Stanford University
2006
Uppsala University
1999
Fibroblast growth factor-21 (FGF21) is a hormone secreted by the liver during fasting that elicits diverse aspects of adaptive starvation response. Among its effects, FGF21 induces hepatic fatty acid oxidation and ketogenesis, increases insulin sensitivity, blocks somatic causes bone loss. Here we show transgenic overexpression markedly extends lifespan in mice without reducing food intake or affecting markers NAD+ metabolism AMP kinase mTOR signaling. Transcriptomic analysis suggests acts...
Leptin action on its receptor (LEPR) stimulates energy expenditure and reduces food intake, thereby lowering body weight. One leptin-sensitive target cell mediating these effects balance is the proopiomelano-cortin (POMC) neuron. Recent evidence suggests that of leptin POMC neurons regulates glucose homeostasis independently balance. Here, we have dissected physiological impact direct using a mouse model in which endogenous LEPR expression was prevented by LoxP-flanked transcription blocker...
Abstract Fibroblast growth factor 21 (FGF21) is a novel metabolic regulator shown to improve glycemic control. However, the molecular and functional mechanisms underlying FGF21-mediated improvements in control are not completely understood. We examined FGF21 effects on insulin sensitivity glucose fluxes upon chronic (daily injection for 8 d) acute (6 h infusion) administration ob/+ ob/ob mice. Results show that ameliorated fasting hyperglycemia mice via increased disposal improved hepatic...
The hormone ghrelin stimulates eating and helps maintain blood glucose upon caloric restriction. While previous studies have demonstrated that hypothalamic arcuate AgRP neurons are targets of ghrelin, the overall relevance signaling within intact is unclear. Here, we tested functional significance action on using a new, tamoxifen-inducible AgRP-CreER(T2) transgenic mouse model allows spatiotemporally-controlled re-expression physiological levels receptors (GHSRs) specifically in adult...
Energy and glucose homeostasis are regulated by central serotonin 2C receptors. These receptors attractive pharmacological targets for the treatment of obesity; however, identity receptor-expressing neurons that mediate effects receptor agonists on energy unknown. Here, we show mice lacking (Htr2c) specifically in pro-opiomelanocortin (POMC) had normal body weight but developed glucoregulatory defects including hyperinsulinemia, hyperglucagonemia, hyperglycemia, insulin resistance. Moreover,...
Acetyl-CoA carboxylase (ACC) promotes prandial liver metabolism by producing malonyl-CoA, a substrate for de novo lipogenesis and an inhibitor of CPT-1-mediated fat oxidation. We report that inhibition ACC also produces unexpected secondary effects on metabolism. Liver-specific double ACC1/2 knockout (LDKO) or pharmacologic increased anaplerosis, tricarboxylic acid (TCA) cycle intermediates, gluconeogenesis activating hepatic CPT-1 pyruvate flux in the fed state. Fasting should have...
To characterize differences in whole-body glucose metabolism between commonly used inbred mouse strains.Hyperinsulinemic-euglycemic (approximately 8.5 mmol/l) and -hypoglycemic 3.0 clamps were done catheterized, 5-h-fasted mice to assess insulin action hypoglycemic counter-regulatory responsiveness. Hyperglycemic 15 secretion compared with results perifused islets.Insulin secretory phenotypes varied considerably four strains. In vivo was greatest 129X1/Sv mice, but the response hypoglycemia...
To determine unambiguously if suppression of glucagon action will eliminate manifestations diabetes, we expressed receptors in livers receptor-null (GcgR(-/-)) mice before and after β-cell destruction by high-dose streptozotocin. Wild type (WT) developed fatal diabetic ketoacidosis streptozotocin, whereas GcgR(-/-) with similar remained clinically normal without hyperglycemia, impaired glucose tolerance, or hepatic glycogen depletion. Restoration receptor expression using adenovirus...
The transcription factor FOXO1 plays a central role in metabolic homeostasis by regulating leptin and insulin activity many cell types, including neurons. However, the neurons mediating these effects identity of molecular targets through which regulates metabolism remain to be defined. Here, we show that ventral medial nucleus hypothalamus (VMH) is key site action. We found mice lacking steroidogenic 1 (SF-1) VMH are lean due increased energy expenditure. also failed appropriately suppress...
The hepatic energy state, defined by adenine nucleotide levels, couples metabolic pathways with requirements. This coupling is fundamental in the adaptive response to many conditions and impaired disease. We have found that state substantially reduced following exercise, fasting, exposure other stressors C57BL/6 mice. Glucagon receptor signaling was hypothesized mediate this reduction because increased plasma levels of glucagon are characteristic stress hormone stimulates consumption linked...
Hepatic glucagon action increases in response to accelerated metabolic demands and is associated with increased whole body substrate availability, including circulating lipids. The hypothesis that hepatic stimulate AMP-activated protein kinase (AMPK) signaling peroxisome proliferator-activated receptor-α (PPARα) fibroblast growth factor 21 (FGF21) expression a manner modulated by fatty acids was tested vivo. Wild-type (gcgr(+/+)) receptor-null (gcgr(-/-)) littermate mice were studied using...
Significance Diet-induced type 2 diabetes (T2D) is becoming a worldwide epidemic. Patients with T2D fail to respond insulin normally and have elevated blood glucose insulin. In autoimmune diabetes, due uncontrolled glucagon, hormone suppressed opposed by To study the role of glucagon in T2D, rodent models disease were created lacking action. These animals failed develop hyperglycemia unless action was restored or given high concentrations typical T2D. This indicates that unopposed necessary...
Abstract Circulating carbohydrates are an essential energy source, perturbations in which pathognomonic of various diseases, diabetes being the most prevalent. Yet many genes underlying and its characteristic hyperglycaemia remain elusive. Here we use physiological genetic interrogations D. melanogaster to uncover ‘glucome’, complete set involved glucose regulation flies. Partial genomic screens ∼1,000 yield ∼160 ‘flyabetes’ candidates that classify using fat body- muscle-specific knockdown...