A5033541238- Diet and metabolism studies
- Adipose Tissue and Metabolism
- Diet, Metabolism, and Disease
- Liver Disease Diagnosis and Treatment
- Cardiovascular Function and Risk Factors
- Metabolism and Genetic Disorders
- Metabolomics and Mass Spectrometry Studies
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Mitochondrial Function and Pathology
- Estrogen and related hormone effects
- Metabolism, Diabetes, and Cancer
- Cancer, Hypoxia, and Metabolism
- Pancreatic function and diabetes
- Epigenetics and DNA Methylation
- Biochemical Acid Research Studies
- Birth, Development, and Health
- Pregnancy and preeclampsia studies
- Gut microbiota and health
- Nuclear Receptors and Signaling
- Diabetes and associated disorders
- Endoplasmic Reticulum Stress and Disease
- Peroxisome Proliferator-Activated Receptors
- RNA modifications and cancer
- Genetic Neurodegenerative Diseases
- Dietary Effects on Health
University of Minnesota
2018-2025
University of Minnesota Medical Center
2025
University of Minnesota System
2024
Institute of Molecular Medicine
2018-2023
Institute of Molecular Biology and Biophysics
2022-2023
Sanford Burnham Prebys Medical Discovery Institute
2014-2020
Discovery Institute
2016-2020
American College of Cardiology
2018
BG University Hospital Bergmannsheil Bochum
2018
Palo Alto Institute
2018
Background— Significant evidence indicates that the failing heart is energy starved. During development of failure, capacity to utilize fatty acids, chief fuel, diminished. Identification alternate pathways for myocardial fuel oxidation could unveil novel strategies treat failure. Methods and Results— Quantitative mitochondrial proteomics was used identify metabolic derangements occur during cardiac hypertrophy failure in well-defined mouse models. As expected, amounts proteins involved acid...
The orphan nuclear receptor steroidogenic factor 1 (SF-1) is expressed in the adrenal cortex and gonads regulates expression of several P450 steroid hydroxylases vitro. We examined role SF-1 glands vivo by a targeted disruption mouse gene. All SF-1-deficient mice died shortly after delivery. Their were absent, persistent Mullerian structures found all genotypic males. While serum levels corticosterone diminished, adrenocorticotropic hormone (ACTH) elevated, consistent with intact pituitary...
Evidence has emerged that the failing heart increases utilization of ketone bodies. We sought to determine whether this fuel shift is adaptive. Mice rendered incapable oxidizing body 3-hydroxybutyrate (3OHB) in exhibited worsened failure response fasting or a pressure overload/ischemic insult compared with WT controls. Increased delivery 3OHB ameliorated pathologic cardiac remodeling and dysfunction mice canine pacing model progressive failure. was shown enhance bioenergetic thermodynamics...
Ketone bodies play significant roles in organismal energy homeostasis, serving as oxidative fuels, modulators of redox potential, lipogenic precursors, and signals, primarily during states low carbohydrate availability. Efforts to enhance wellness ameliorate disease via nutritional, chronobiological, pharmacological interventions have markedly intensified interest ketone body metabolism. The two partners, acetoacetate D-β-hydroxybutyrate, serve distinct metabolic signaling biological...
Environmental nutrient availability influences T cell metabolism, impacting function and shaping immune outcomes. Here, we identified ketone bodies (KBs)-including β-hydroxybutyrate (βOHB) acetoacetate (AcAc)-as essential fuels supporting CD8
The orphan nuclear receptor steroidogenic factor 1 (SF-1) is a critical developmental regulator in the urogenital ridge, because mice targeted for disruption of SF-1 gene lack adrenal glands and gonads. was recently shown to interact with DAX-1, another whose tissue distribution overlaps that SF-1. Naturally occurring loss-of-function mutations DAX-1 cause human disorder X-linked hypoplasia congenita (AHC), which resembles phenotype SF-1-deficient mice. Paradoxically, however, represses...
Sympathetic axons use blood vessels as an intermediate path to reach their final target tissues. The initial contact between differentiating sympathetic neurons and occurs following the primary chain formation, where precursors of migrate project along or toward vessels. We demonstrate that, in Ret-deficient mice, neuronal throughout entire nervous system fail properly. These deficits lead mis-routing nerve trunks accelerated cell death later development. Artemin is expressed during periods...
Studies in mice indicate that the gut microbiota promotes energy harvest and storage from components of diet when these are plentiful. Here we examine how shapes host metabolic physiologic adaptations to periods nutrient deprivation. Germ-free (GF) who had received a transplant conventionally raised donors were compared fed fasted states by using functional genomic, biochemical, assays. A 24-h fast produces marked change microbial ecology. Short-chain fatty acids generated fermentation...
We describe a method for treating germ-free (GF) mice with gamma-irradiation and transplanting them normal or genetically manipulated bone marrow while maintaining their GF status. This approach revealed that are markedly resistant to lethal radiation enteritis. Furthermore, administering doses of total body irradiation produces fewer apoptotic endothelial cells lymphocytes in the mesenchymal cores small intestinal villi, compared conventionally raised animals have acquired microbiota from...
Nonalcoholic fatty liver disease (NAFLD) spectrum disorders affect approximately 1 billion individuals worldwide. However, the drivers of progressive steatohepatitis remain incompletely defined. Ketogenesis can dispose much fat that enters liver, and dysfunction in this pathway could promote development NAFLD. Here, we evaluated mice lacking mitochondrial 3-hydroxymethylglutaryl CoA synthase (HMGCS2) to determine role ketogenesis preventing diet-induced steatohepatitis. Antisense...
Objective: Exploitation of protective metabolic pathways within injured myocardium still remains an unclarified therapeutic target in heart disease.Moreover, while the roles altered fatty acid and glucose metabolism failing have been explored, influence highly dynamic nutritionally modifiable ketone body regulation myocardial substrate utilization, mitochondrial bioenergetics, reactive oxygen species (ROS) generation, hemodynamic response to injury undefined.Methods: Here we use mice that...
Low-carbohydrate diets are used to manage obesity, seizure disorders, and malignancies of the central nervous system. These create a distinctive, but incompletely defined, cellular, molecular, integrated metabolic state. Here, we determine systemic hepatic effects long-term administration very low-carbohydrate, low-protein, high-fat ketogenic diet, serially comparing these high-simple-carbohydrate, Western diet low-fat, polysaccharide-rich control chow in C57BL/6J mice. Longitudinal...
Studies of isotopically labeled compounds have been fundamental to understanding metabolic pathways and fluxes. They traditionally, however, used in conjunction with targeted analyses that identify quantify a limited number downstream metabolites. Here we describe an alternative workflow leverages recent advances untargeted metabolomic technologies track the fates metabolites global, unbiased manner. This approach can be applied discover novel biochemical characterize changes as function...
Heart failure (HF) is associated with metabolic perturbations, particularly of fatty acids (FAs), which remain to be better understood in humans. This study aimed at testing the hypothesis that HF patients reduced ejection fraction display systemic perturbations levels energy-related metabolites, especially those reflecting dysregulation FA metabolism, namely, acylcarnitines (ACs). Circulating metabolites were assessed using mass spectrometry (MS)-based methods two cohorts. The main cohort...
Abstract Extensive research has demonstrated endurance exercise to be neuroprotective. Whether these neuroprotective benefits are mediated, in part, by hepatic ketone production remains unclear. To investigate the role of on brain health during exercise, healthy 6‐month‐old female rats underwent viral knockdown rate‐limiting enzyme liver that catalyses first reaction ketogenesis: 3‐hydroxymethylglutaryl‐CoA synthase 2 (HMGCS2). Rats were then subjected either a bout acute or 4 weeks chronic...