- Peroxisome Proliferator-Activated Receptors
- Adipose Tissue and Metabolism
- Cancer, Lipids, and Metabolism
- Adipokines, Inflammation, and Metabolic Diseases
- Lipid metabolism and biosynthesis
- Metabolomics and Mass Spectrometry Studies
- Metabolism, Diabetes, and Cancer
- Immune cells in cancer
- Bariatric Surgery and Outcomes
- Metabolism and Genetic Disorders
- Diet and metabolism studies
- Inflammatory mediators and NSAID effects
- Redox biology and oxidative stress
- Receptor Mechanisms and Signaling
- Protein Kinase Regulation and GTPase Signaling
- Retinoids in leukemia and cellular processes
- Immune Response and Inflammation
- Antioxidant Activity and Oxidative Stress
- Protein Structure and Dynamics
- Cancer, Hypoxia, and Metabolism
- Drug Transport and Resistance Mechanisms
- Mitochondrial Function and Pathology
- Cardiovascular Disease and Adiposity
- Lipid Membrane Structure and Behavior
- Enzyme Structure and Function
University of Minnesota
2016-2025
University of Minnesota System
2013-2024
Twin Cities Orthopedics
1999-2024
Institute of Molecular Biology and Biophysics
1992-2022
Washington University in St. Louis
2019
National and Kapodistrian University of Athens
2017
American Diabetes Association
2015
Agruicultural Research Institute
2014
Minneapolis Institute of Arts
2013-2014
Nirma (India)
2012
To identify and characterize specific mRNAs that increase in abundance during differentiation of mouse 3T3-L1 preadipocytes, a cDNA library was constructed from poly(A)+RNA isolated differentiated adipocytes. Mixed probe isotope ratio selection RNA blot analyses have identified several unique clones represent mRNA species expressed either exclusively or at dramatically increased levels cells. Further characterization one such clone (pAL422) revealed the corresponding mRNA, detectable only...
Adipose tissue-derived cytokines (adipokines) are associated with the development of inflammation and insulin resistance. However, which adipokine(s) mediate this linkage mechanisms involved during obesity is poorly understood. Through proteomics microarray screening, we recently identified lipocalin 2 (LCN 2) as an adipokine that potentially connects its related adipose inflammation. Herein show levels LCN2 mRNA dramatically increased in tissue liver ob/ob mice primary cells isolated from...
Insulin regulates heart metabolism through the regulation of insulin-stimulated glucose uptake. Studies have indicated that insulin can also regulate mitochondrial function. Relevant to this idea, function is impaired in diabetic individuals. Furthermore, expression Opa-1 and mitofusins, proteins fusion machinery, dramatically altered obese insulin-resistant patients. Given role control cardiac energetics, goal study was investigate whether affects dynamics cardiomyocytes. Confocal...
Differentiation of 3T3-L1 preadipocytes in culture is accompanied by alterations the abundance several mRNAs and appearance many new adipocyte-specific mRNAs. To investigate processes responsible for these alterations, kinetics accumulation specific were compared with their respective rates nuclear runoff transcription. The fructose-1,6-bisphosphate aldolase an unidentified 4800-base mRNA increase only moderately (2-4-fold) during differentiation. Runoff transcription nuclei isolated from...
The availability of mice containing an adipocyte lipid-binding protein (ALBP/aP2) gene disruption allowed for a direct examination the presumed role proteins in mobilization and trafficking intracellular fatty acids. Total body epididymal fat pad weights, as well adipose cell morphology, were unaltered male ALBP/aP2 disrupted when compared to their wild-type littermates. Analysis adipocytes isolated from null revealed that selective 40- 13-fold increase level keratinocyte (KLBP) mRNA...
Fatty acid transport protein (FATP), a plasma membrane implicated in controlling adipocyte transmembrane fatty flux, is up-regulated as consequence of differentiation and down-regulated by insulin. Based upon the sequence FATP gene upstream region (Hui, T. Y., Frohnert, B. I., Smith, A. J., Schaffer, J. A., Bernlohr, D. (1998) Biol. Chem. 273, 27420–27429) putative peroxisome proliferator-activated receptor response element (PPRE) present from −458 to −474. To determine whether PPRE was...
Obesity is a state of mild inflammation correlated with increased oxidative stress. In general, pro-oxidative conditions lead to production reactive aldehydes such as trans-4-hydroxy-2-nonenal (4-HNE) and trans-4-oxo-2-nonenal implicated in the development variety metabolic diseases. To investigate protein modification by 4-HNE consequence obesity its potential relationship insulin resistance, proteomics technologies were utilized identify aldehyde-modified proteins adipose tissue. Adipose...
The primary sequence of the murine fatty acid transport protein (FATP1) is very similar to multigene family long chain (C20-C26) acyl-CoA synthetases. To determine if FATP1 a acyl coenzyme A synthetase, FATP1-Myc/His fusion was expressed in COS1 cells, and its enzymatic activity analyzed. In addition, mutations were generated two domains conserved synthetases: 6- amino substitution into putative active site (amino acids 249–254) generating mutant M1 59-amino deletion C-terminal domain...
The metabolic syndrome is a cluster of and inflammatory abnormalities including obesity, insulin resistance, type 2 diabetes, hypertension, dyslipidemia, atherosclerosis. fatty acid binding proteins aP2 (fatty protein [FABP]-4) mal1 (FABP5) are closely related both expressed in adipocytes. Previous studies aP2-deficient mice have indicated significant role for obesity-related However, the biological functions not known. Here, we report generation with targeted null mutations gene as well...
OBJECTIVE Peripheral insulin resistance is linked to an increase in reactive oxygen species (ROS), leading part the production of lipid aldehydes that modify side chains protein amino acids a reaction termed carbonylation. The primary enzymatic method for aldehyde detoxification via glutathione S-transferase A4 (GSTA4) dependent glutathionylation. objective this study was evaluate expression GSTA4 and role(s) carbonylation adipocyte function. RESEARCH DESIGN AND METHODS GSTA4-silenced 3T3-L1...
OBJECTIVE Lipocalin (LCN) 2 belongs to the lipocalin subfamily of low–molecular mass–secreted proteins that bind small hydrophobic molecules. LCN2 has been recently characterized as an adipose-derived cytokine, and its expression is upregulated in adipose tissue genetically obese rodents. The objective this study was investigate role diet-induced insulin resistance metabolic homeostasis vivo. RESEARCH DESIGN AND METHODS Systemic sensitivity, adaptive thermogenesis, serum lipid profile were...
Hormone-sensitive lipase (HSL) is a cytosolic neutral that functions as the rate-limiting enzyme for mobilization of free fatty acids in adipose tissue. By using yeast two-hybrid system to examine potential interaction HSL with other cellular proteins, evidence provided demonstrate direct adipocyte lipid-binding protein (ALBP), member family intracellular proteins binds acids, retinoids, and hydrophobic ligands. The was demonstrated vitro by binding ALBP translated , extracts overexpressing...
AMP activated protein kinase (AMPK) plays an important role in regulating myocardial metabolism and synthesis. Activation of AMPK attenuates hypertrophy cultured cardiac myocytes, but the development response to chronic pressure overload is not known. To test hypothesis that AMPKalpha2 protects heart against systolic overload-induced ventricular dysfunction, we studied gene deficient (knockout [KO]) mice wild-type subjected 3 weeks transverse aortic constriction (TAC). Although KO had no...
Human placentation entails the remarkable integration of fetal and maternal cells into a single functional unit. In basal plate region (the maternal-fetal interface) placenta, cytotrophoblasts from placenta invade uterus remodel resident vasculature avoid immune rejection. Knowing molecular bases for these unique cell-cell interactions is important understanding how this specialized functions during normal pregnancy with implications tumor biology transplantation immunology. Therefore, we...
An adipose-specific protein has been purified from murine 3T3-L1 adipocytes to greater than 98% homogeneity. A purification procedure was developed utilizing a combination of gel filtration, cation exchange chromatography, and covalent chromatography on activated-thiol Sepharose 4B. The exists as single polypeptide with molecular weight about 15,000, determined by sodium dodecyl sulfate-polyacrylamide electrophoresis. contains 2 mol reduced sulfhydryl groups per an amino terminus blocked...