A5082971980- Adipokines, Inflammation, and Metabolic Diseases
- Adipose Tissue and Metabolism
- Immune Cell Function and Interaction
- Cholesterol and Lipid Metabolism
- Peroxisome Proliferator-Activated Receptors
- Immune cells in cancer
- Regulation of Appetite and Obesity
- Neuroinflammation and Neurodegeneration Mechanisms
- Pancreatic function and diabetes
- Atherosclerosis and Cardiovascular Diseases
- Inflammation biomarkers and pathways
- Diabetes and associated disorders
- Cancer, Lipids, and Metabolism
- Liver Disease Diagnosis and Treatment
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Drug Transport and Resistance Mechanisms
- Cardiovascular Disease and Adiposity
- Diet, Metabolism, and Disease
- Lipid metabolism and disorders
- Iron Metabolism and Disorders
- Metabolism, Diabetes, and Cancer
- Dietary Effects on Health
- Lipid metabolism and biosynthesis
- Exercise and Physiological Responses
- Hemoglobinopathies and Related Disorders
Vanderbilt University
2016-2025
The University of Texas Southwestern Medical Center
2025
Southwestern Medical Center
2025
Vanderbilt University Medical Center
2008-2024
VA Tennessee Valley Healthcare System
2015-2024
United States Department of Veterans Affairs
2023-2024
Creative Commons
2020
University of Illinois Urbana-Champaign
2019
University of California, Davis
2019
University of Oklahoma
2019
To elucidate the physiological role of sterol regulatory element-binding protein-1 (SREBP-1), hepatic mRNA levels genes encoding various lipogenic enzymes were estimated in SREBP-1 gene knockout mice after a fasting-refeeding treatment, which is an established dietary manipulation for induction enzymes. In fasted state, all consistently low both wild-type and<i>SREBP-1</i> <sup>−/−</sup> mice. However, absence severely impaired marked mRNAs fatty acid synthetic genes, such as acetyl-CoA...
AbstractIn an attempt to identify transcription factors which activate sterol-regulatory element-binding protein 1c (SREBP-1c) transcription, we screened expression cDNA library from adipose tissue of SREBP-1 knockout mice using a reporter gene containing the 2.6-kb mouse promoter. We cloned and identified oxysterol receptors liver X receptor (LXRα) LXRβ as strong activators SREBP-1c In transfection studies, either LXRα or -β activated promoter-luciferase in dose-dependent manner. Deletion...
Recent studies on the in vivo roles of sterol regulatory element binding protein (SREBP) family indicate that SREBP-2 is more specific to cholesterogenic gene expression whereas SREBP-1 targets lipogenic genes. To define molecular mechanism involved this differential regulation, luciferase-reporter assays were performed HepG2 cells compare transactivities nuclear SREBP-1a, -1c, and -2 a battery SREBP-target promoters containing (SRE), SRE-like, or E-box sequences. The results show first...
Type 2 diabetes is often accompanied by abnormal blood lipid and lipoprotein levels, but most studies on the link between hyperlipidemia have focused free fatty acids (FFAs). In this study, we examined relationship cholesterol insulin secretion from pancreatic beta-cells that independent of effects FFAs.Several methods were used to modulate levels in intact islets cultured beta-cells, including a recently developed mouse model exhibits elevated normal FFA levels. Acute metabolic alteration...
It has long been known that adipose tissue in obesity is a heightened state of inflammation. Recently, our understanding this transformed by the knowledge immune cells such as macrophages and T can infiltrate are responsible for majority inflammatory cytokine production. These seminal findings have opened up new area biology garnering interest scientists involved research relating to cell motility, inflammation, obesity, physiology, diabetes cardiovascular disease. Some important general...
Abstract Within adipose tissue (AT), immune cells and parenchymal closely interact creating a complex microenvironment. In obesity, cell derived inflammation contributes to insulin resistance glucose intolerance. Diet-induced weight loss improves tolerance; however, regain further exacerbates the impairment in homeostasis observed with obesity. To interrogate immunometabolic adaptations that occur AT during murine regain, we utilized cellular indexing of transcriptomes epitopes by sequencing...
Porous, resorbable biomaterials can serve as temporary scaffolds that support cell infiltration, tissue formation, and remodeling of nonhealing skin wounds. Synthetic are less expensive to manufacture than biologic dressings achieve a broader range physiochemical properties, but opportunities remain tailor these materials for ideal host immune regenerative responses. Polyesters well-established class synthetic biomaterials; however, acidic degradation products released by their hydrolysis...
Dietary polyunsaturated fatty acids (PUFA) are negative regulators of hepatic lipogenesis that exert their effects primarily at the level transcription. Sterol regulatory element-binding proteins (SREBPs) transcription factors responsible for regulation cholesterol, acid, and triglyceride synthesis. In particular, SREBP-1 is known to play a crucial role in lipogenic gene expression liver. To explore possible involvement suppression by PUFA, we challenged wild-type mice transgenic...
In the process of seeking sterol regulatory element-binding protein 1a (SREBP-1a) target genes, we identified and cloned a cDNA clone encoding mouse Δ5-desaturase (D5D). The hepatic expression D5D as well Δ6-desaturase (D6D) was highly activated in transgenic mice overexpressing nuclear SREBP-1a, -1c, -2. Disruption SREBP-1 gene significantly reduced both desaturases livers SREBP-1-deficient refed after fasting. downregulated by dietary PUFA, which were reported to suppress SREBP-1c...
Macrophage-derived foam cells express apolipoprotein E (apoE) abundantly in atherosclerotic lesions. To examine the physiologic role of apoE secretion by macrophage atherogenesis, bone marrow transplantation was used to reconstitute C57BL/6 mice with macrophages that were either null or wild type for gene. After 13 weeks on an atherogenic diet, reconstituted developed 10-fold more atherosclerosis than controls absence significant differences serum cholesterol levels lipoprotein profiles....
Recent data suggest that sterol regulatory-binding protein (SREBP)-1c plays a key role in the transcriptional regulation of different lipogenic genes mediating lipid synthesis as regulator fuel metabolism. SREBP-1c regulates its downstream by changing own mRNA level, which led us to sequence and analyze promoter region mouse gene. A cluster putative binding sites several transcription factors composed an NF-Y site, E-box, sterol-regulatory element 3, Sp1 site were located at −90 base pairs...
Leptin-deficient mice (ob/ob) are an excellent murine model for obesity, insulin resistance, and diabetes, all of which components a multiple risk factor syndrome that, along with hypercholesterolemia, precipitates potential high atherosclerosis. In the current study, we show unexpectedly severe hyperlipidemia in ob/ob on background low density lipoprotein receptor (LDLR) deficiency (−/−). Doubly mutant (LDLR−/−;ob/ob) exhibited striking elevations both total plasma cholesterol (TC)...
The mammalian enzyme involved in the final elongation of de novo fatty acid biosynthesis following building acids to 16 carbons by synthase has yet be identified. In process searching for genes activated sterol regulatory element-binding protein 1 (SREBP-1) using DNA microarray, we identified and characterized a murine cDNA clone that is highly similar acyl-CoA elongase gene family such as Cig30, Sscs, yeast ELOs. Studies on cells overexpressing full-length indicate encoded protein,...
Insulin and glucose together have been previously shown to regulate hepatic sterol regulatory element-binding protein (SREBP)-1c expression. We sought explore the nutritional regulation of lipogenesis through SREBP-1c induction in a setting where effects sugars versus insulin could be distinguished. To do so, mice were depleted by streptozotocin (STZ) administration subjected fasting-refeeding protocol with glucose, fructose, or sucrose. Unexpectedly, insulin-depleted exhibited marked on all...