A5052952272- Adipose Tissue and Metabolism
- Adipokines, Inflammation, and Metabolic Diseases
- Endoplasmic Reticulum Stress and Disease
- Pancreatic function and diabetes
- Cardiovascular Disease and Adiposity
- Angiogenesis and VEGF in Cancer
- Atherosclerosis and Cardiovascular Diseases
- Autophagy in Disease and Therapy
- MicroRNA in disease regulation
- Immune cells in cancer
- Sirtuins and Resveratrol in Medicine
- Chemokine receptors and signaling
- Nuclear Structure and Function
- Diabetes and associated disorders
- Metabolism, Diabetes, and Cancer
- Exercise and Physiological Responses
- Sperm and Testicular Function
- Nuclear Receptors and Signaling
- Nerve injury and regeneration
- Calcium signaling and nucleotide metabolism
- Fibroblast Growth Factor Research
- Kruppel-like factors research
- Reproductive Biology and Fertility
University of Oklahoma Health Sciences Center
2017-2025
Iowa Diabetes and Endocrinology Research Center
2021
Oklahoma Medical Research Foundation
2012-2015
Mitochondrial remodeling is dysregulated in metabolic diseases but the underlying mechanism not fully understood. We report here that BDNF (brain derived neurotrophic factor) provokes mitochondrial fission and clearance skeletal muscle via PRKAA/AMPK-PINK1-PRKN/Parkin PRKAA-DNM1L/DRP1-MFF pathways. Depleting Bdnf expression myotubes reduced fatty acid-induced mitofission mitophagy, which was associated with elongation impaired lipid handling. Muscle-specific bdnf knockout (MBKO) mice...
BDNF produced by skeletal muscle in female mice enables switching of fuel sources during fasting.
Overnutrition engenders the expansion of adipose tissue and accumulation immune cells, in particular, macrophages, tissue, leading to chronic low-grade inflammation insulin resistance. In obesity, several proinflammatory subpopulations macrophages (ATMs) identified hitherto include conventional “M1-like” CD11C-expressing ATM newly discovered metabolically activated CD9-expressing ATM; however, relationship among is unclear. The ER stress sensor inositol-requiring enzyme 1α (IRE1α) adipocytes...
Overnutrition engenders the expansion of adipose tissue and accumulation immune cells, in particular, macrophages, tissue, leading to chronic low-grade inflammation insulin resistance. In obesity, several proinflammatory subpopulations macrophages (ATMs) identified hitherto include conventional “M1-like” CD11C-expressing ATM newly discovered metabolically activated CD9-expressing ATM; however, relationship among is unclear. The ER stress sensor inositol-requiring enzyme 1α (IRE1α) adipocytes...
Overnutrition engenders the expansion of adipose tissue and accumulation immune cells, in particular, macrophages, tissue, leading to chronic low-grade inflammation insulin resistance. In obesity, several proinflammatory subpopulations macrophages (ATMs) identified hitherto include conventional ‘M1-like’ CD11C-expressing ATM newly discovered metabolically activated CD9-expressing ATM; however, relationship among is unclear. The ER stress sensor inositol-requiring enzyme 1α (IRE1α) adipocytes...
The major event initiating atherosclerosis is hypercholesterolemia-induced disruption of vascular endothelium integrity. In settings endothelial damage, progenitor cells (EPCs) are mobilized from bone marrow into circulation and home to sites injury where they aid regeneration. Given the beneficial effects EPCs in repair, we hypothesized that these play a pivotal role regression. We tested our hypothesis atherosclerosis-prone mouse model which hypercholesterolemia, one main factors affecting...
The chemokine receptor CXCR4 is expressed on adipocytes and macrophages in adipose tissue, but its role this tissue remains unknown. We evaluated whether deficiency either adipocyte or myeloid leukocyte affects body weight (BW) adiposity a mouse model of high-fat-diet (HFD)-induced obesity. found that ablation adipocyte, not leukocyte, exacerbated HFD-fed adipocyte-specific CXCR4-knockout (AdCXCR4ko) mice, compared to wild-type C57BL/6 control had increased BW (average: 52.0 g vs. 35.5 g),...
Background and Aims: Metabolism in the liver is dysregulated obesity, contributing to various health problems including steatosis insulin resistance. While pathogenesis of lipid accumulation has been extensively studied, protective mechanism against challenge remains unclear. Here, we report that Src homology 3 domain binding kinase 1 (SBK1) a regulator hepatic metabolism systemic sensitivity response obesity. Approach Results: Enhanced Sbk1 expression was found high‐fat diet (HFD)–induced...
AimsAtherosclerosis manifests itself as arterial plaques, which lead to heart attacks or stroke. Treatments supporting plaque regression are therefore aggressively pursued. Studies conducted in models hypercholesterolaemia is reversible, such the Reversa mouse model we have employed current studies, will be instrumental for development of interventions. Using this model, shown that advanced atherosclerosis occurs when lipid lowering used combination with bone-marrow endothelial progenitor...
Tumor necrosis factor-α (TNF-α) is an inflammatory cytokine that plays a central role in obesity-induced insulin resistance. It also controls cellular lipid metabolism, but the underlining mechanism poorly understood. We report this study phosphoinositide 3-kinase enhancer A (PIKE-A) novel effector of TNF-α to facilitate its metabolic modulation skeletal muscle. Depletion PIKE-A C2C12 myotubes diminished inhibitory activities on mitochondrial respiration and oxidation, whereas overexpression...
Overnutrition engenders the expansion of adipose tissue and accumulation immune cells, in particular, macrophages, tissue, leading to chronic low-grade inflammation insulin resistance. In obesity, several proinflammatory subpopulations macrophages (ATMs) identified hitherto include conventional "M1-like" CD11C-expressing ATM newly discovered metabolically activated CD9-expressing ATM; however, relationship among is unclear. The ER stress sensor inositol-requiring enzyme 1α (IRE1α) adipocytes...
Thermogenic brown or beige adipocytes dissipate energy in the form of heat and thereby counteract obesity related metabolic complications. The miRNA cluster miR-130b/301b is highly expressed adipose tissues has been implicated diseases as a posttranscriptional regulator mitochondrial biogenesis lipid metabolism. We investigated roles regulating adipogenesis vivo vitro. declined progenitor cells during adipogenesis, while forced overexpression miR-130b-3p miR-301b-3p suppressed uncoupling...
Ribonuclease, RNase A family, 9 (RNASE9) is a ribonuclease superfamily member that expressed only in the epididymis. It small, secreted polypeptide, it lacks activity, and its function(s) unknown. However, epididymis-specific expression suggests role sperm maturation. We generated Rnase9−/− mice to study RNASE9 function vivo. confirm restricted Within epididymis, first detected midcaput, persists through distal caput corpus, wanes cauda. are born at expected Mendelian ratio, have normal...
Overnutrition engenders the expansion of adipose tissue and accumulation immune cells, in particular, macrophages, tissue, leading to chronic low-grade inflammation insulin resistance. In obesity, several proinflammatory subpopulations macrophages (ATMs) identified hitherto include conventional “M1-like” CD11C-expressing ATM newly discovered metabolically activated CD9-expressing ATM; however, relationship among is unclear. The ER stress sensor inositol-requiring enzyme 1α (IRE1α) adipocytes...
β-cell ER stress plays an important role in dysfunction and death during the pathogenesis of diabetes. Proinsulin misfolding is regarded as one primary initiating factors unfolded protein response (UPR) activation β-cells. Here, we found that sensor inositol-requiring enzyme 1α (IRE1α) was activated Akita mice, a mouse model mutant insulin gene-induced diabetes youth (MIDY), monogenic Normalization IRE1α RNase hyperactivity by pharmacological inhibitors significantly ameliorated...
Atherosclerosis is a major cause of morbidity and mortality in the United States. Persistently elevated circulating low-density lipoprotein, or hypercholesterolemia, deposition lipoprotein vascular wall are main inducers atherosclerosis, which manifests itself as arterial lesions plaques. Some plaques become thrombosis-prone rupture, causing acute myocardial infarction stroke. Lowering plasma cholesterol through use statins primary intervention against atherosclerosis. Treatment with slows...
Overnutrition engenders the expansion of adipose tissue and accumulation immune cells, in particular, macrophages, tissue, leading to chronic low-grade inflammation insulin resistance. In obesity, several proinflammatory subpopulations macrophages (ATMs) identified hitherto include conventional “M1-like” CD11C-expressing ATM newly discovered metabolically activated CD9-expressing ATM; however, relationship among is unclear. The ER stress sensor inositol-requiring enzyme 1α (IRE1α) adipocytes...
Endoplasmic reticulum (ER) stress-induced pancreatic β-cell dysfunction and death play important roles in the development of diabetes. The 1,2,3-triazole derivative 1 is one only a few structures that have thus far been identified protect β cells against ER stress. However, this compound has narrow activity range limited aqueous solubility. To overcome these, we designed synthesized new scaffold which triazole pharmacophore was substituted with glycine-like amino acid. Structure-activity...
ABSTRACT Proinsulin misfolding in the endoplasmic reticulum (ER) plays an important role β-cell dysfunction and death pathogenesis of mutant INS -gene-induced diabetes youth (MIDY). There is no effective treatment for MIDY except insulin administration. Here, we found that ER stress sensor inositol-requiring enzyme 1α (IRE1α) was activated Akita mice, a mouse model MIDY. Normalization IRE1α RNase hyperactivity by pharmacological inhibitors significantly ameliorated hyperglycemic conditions...
Abstract Endoplasmic reticulum (ER) stress‐induced Pancreatic β‐cell dysfunction and death plays important roles in the development of diabetes. The 1,2,3‐triazole derivative 1 is one only a few structures that have thus far been identified protect β cells against ER stress, but it limited for its narrow activity range. In this study, we designed synthesized series hydroxybenzamide (HBA) derivatives which triazole pharmacophore was substituted with an amide linker. Structure–activity...