Articles by Laurie J. Minze in JoVE
Functionele Beeldvorming van bruin vet in Muizen met FDG micro-PET/CT Xukui Wang1, Laurie J. Minze2, Zheng-Zheng Shi1 1Department of Translational Imaging, The Methodist Hospital Research Institute, Houston, 2Diabetes Research Center, The Methodist Hospital Research Institute, Houston Werkwijze van functionele beeldvorming van muis bruin vetweefsel (BAT) beschreven waarin koud-gestimuleerde opname van 18F-Fluorodeoxyglucose (FDG) in BAT niet-invasief gemeten met een gestandaardiseerd protocol micro-PET/CT. Deze methode is robuust en gevoelig zijn voor verschillen in BAT activiteiten in muismodellen detecteren.
Other articles by Laurie J. Minze on PubMed
Rosiglitazone Attenuates Age- and Diet-associated Nonalcoholic Steatohepatitis in Male Low-density Lipoprotein Receptor Knockout Mice Hepatology (Baltimore, Md.). Dec, 2010 | Pubmed ID: 20938947 Nonalcoholic fatty liver disease (NAFLD) is a common complication of obesity that can progress to nonalcoholic steatohepatitis (NASH), a serious liver pathology that can advance to cirrhosis. The mechanisms responsible for NAFLD progression to NASH remain unclear. Lack of a suitable animal model that faithfully recapitulates the pathophysiology of human NASH is a major obstacle in delineating mechanisms responsible for progression of NAFLD to NASH and, thus, development of better treatment strategies. We identified and characterized a novel mouse model, middle-aged male low-density lipoprotein receptor (LDLR)(-/-) mice fed a high-fat diet (HFD), which developed NASH associated with four of five metabolic syndrome (MS) components. In these mice, as observed in humans, liver steatosis and oxidative stress promoted NASH development. Aging exacerbated the HFD-induced NASH such that liver steatosis, inflammation, fibrosis, oxidative stress, and liver injury markers were greatly enhanced in middle-aged versus young LDLR(-/-) mice. Although expression of genes mediating fatty acid oxidation and antioxidant responses were up-regulated in young LDLR(-/-) mice fed HFD, they were drastically reduced in MS mice. However, similar to recent human trials, NASH was partially attenuated by an insulin-sensitizing peroxisome proliferator-activated receptor-gamma (PPARÎ³) ligand, rosiglitazone. In addition to expected improvements in MS, newly identified mechanisms of PPARÎ³ ligand effects included stimulation of antioxidant gene expression and mitochondrial Î²-oxidation, and suppression of inflammation and fibrosis. LDLR-deficiency promoted NASH, because middle-aged C57BL/6 mice fed HFD did not develop severe inflammation and fibrosis, despite increased steatosis. Conclusion: MS mice represent an ideal model to investigate NASH in the context of MS, as commonly occurs in human disease, and NASH development can be substantially attenuated by PPARÎ³ activation, which enhances Î²-oxidation.
Myeloid Deletion of Nuclear Factor Erythroid 2-related Factor 2 Increases Atherosclerosis and Liver Injury Arteriosclerosis, Thrombosis, and Vascular Biology. Dec, 2012 | Pubmed ID: 23023374 To determine the impact of hematopoietic deletion of nuclear factor- (erythroid-derived 2) like 2 factor (Nrf2) on the development of atherosclerosis and liver injury in an obese, hypercholesterolemic mouse model.
The Clock Gene, Brain and Muscle Arnt-like 1, Regulates Adipogenesis Via Wnt Signaling Pathway FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology. Aug, 2012 | Pubmed ID: 22611086 Circadian clocks in adipose tissue are known to regulate adipocyte biology. Although circadian dysregulation is associated with development of obesity, the underlying mechanism has not been established. Here we report that disruption of the clock gene, brain and muscle Arnt-like 1 (Bmal1), in mice led to increased adipogenesis, adipocyte hypertrophy, and obesity, compared to wild-type (WT) mice. This is due to its cell-autonomous effect, as Bmal1 deficiency in embryonic fibroblasts, as well as stable shRNA knockdown (KD) in 3T3-L1 preadipocyte and C3H10T1/2 mesenchymal stem cells, promoted adipogenic differentiation. We demonstrate that attenuation of Bmal1 function resulted in down-regulation of genes in the canonical Wnt pathway, known to suppress adipogenesis. Promoters of these genes (Wnt10a, Î²-catenin, Dishevelled2, TCF3) displayed Bmal1 occupancy, indicating direct circadian regulation by Bmal1. As a result, Wnt signaling activity was attenuated by Bmal1 KD and augmented by its overexpression. Furthermore, stabilizing Î²-catenin through Wnt ligand or GSK-3Î² inhibition achieved partial restoration of blunted Wnt activity and suppression of increased adipogenesis induced by Bmal1 KD. Taken together, our study demonstrates that Bmal1 is a critical negative regulator of adipocyte development through transcriptional control of components of the canonical Wnt signaling cascade, and provides a mechanistic link between circadian disruption and obesity.