A5009855355- Adipose Tissue and Metabolism
- Fibroblast Growth Factor Research
- Adipokines, Inflammation, and Metabolic Diseases
- Kruppel-like factors research
- Epigenetics and DNA Methylation
- Exercise and Physiological Responses
- Cardiovascular Disease and Adiposity
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- Inflammatory Biomarkers in Disease Prognosis
- Metabolism, Diabetes, and Cancer
- Fatty Acid Research and Health
- Receptor Mechanisms and Signaling
- Erythrocyte Function and Pathophysiology
- MicroRNA in disease regulation
- GDF15 and Related Biomarkers
- Renin-Angiotensin System Studies
- Diet and metabolism studies
- Platelet Disorders and Treatments
- Dietary Effects on Health
- Pancreatic function and diabetes
- Circular RNAs in diseases
- Regulation of Appetite and Obesity
- 3D Printing in Biomedical Research
- Biomarkers in Disease Mechanisms
University of Iowa
2014-2020
Fraternal Order of Eagles
2014-2020
Harvard University
2012-2015
Joslin Diabetes Center
2012-2015
University of Chicago
2005-2010
Diabetes Australia
2010
Brown adipose tissue (BAT) is known to function in the dissipation of chemical energy response cold or excess feeding, and also has capacity modulate balance. To test hypothesis that BAT fundamental regulation glucose homeostasis, we transplanted from male donor mice into visceral cavity age- sex-matched recipient mice. By 8–12 weeks following transplantation, had improved tolerance, increased insulin sensitivity, lower body weight, decreased fat mass, a complete reversal high-fat...
Fibroblast growth factor (FGF)21 is an endocrine hormone that expressed in multiple tissues and functions physiologically to maintain energy homeostasis. FGF21 being pursued as a therapeutic target for diabetes obesity because of its rapid potent effects on improving insulin sensitivity. However, whether enhances sensitivity under physiologic conditions remains unclear. Here, we show liver-derived enters the circulation during fasting but also present functional early stage refeeding. After...
Exercise training improves whole-body glucose homeostasis through effects largely attributed to adaptations in skeletal muscle; however, also affects other tissues, including adipose tissue. To determine whether exercise-induced tissue contribute training-induced improvements homeostasis, subcutaneous white (scWAT) from exercise-trained or sedentary donor mice was transplanted into the visceral cavity of recipients. Remarkably, 9 days post-transplantation, receiving scWAT had improved...
Abstract Obesity is associated with an increased risk of developing breast cancer and also worse clinical prognosis. The mechanistic link between obesity progression remains unclear, there has been no development specific treatments to improve the outcome obese patients. Here we show that obesity-associated NLRC4 inflammasome activation/ interleukin (IL)-1 signalling promotes progression. tumour microenvironment in context induces increase tumour-infiltrating myeloid cells activated turn...
The peroxisome proliferator-activated receptor gamma (PPARgamma) is a central regulator of adipogenesis and recruits coactivator proteins in response to ligand. However, the role another class nuclear cofactors, corepressors, modulating PPARgamma transcriptional activity less clear. Such corepressors include corepressor (NCoR) silencing mediator retinoid thyroid hormone receptors (SMRT). Our data suggest that SMRT NCoR absence ligand these are capable down-regulating PPARgamma-mediated...
Abstract Adipose tissue dysfunction is critical to the development of type II diabetes and other metabolic diseases. While monolayer cell culture has been useful for studying fat biology, 2D often does not reflect complexity tissue. Animal models are also problematic in that they expensive, time consuming, may completely recapitulate human biology because species variation. To address these problems, we have developed a scaffold-free method generate 3D adipose spheroids from primary or...
Fibroblast Growth Factor 21 (FGF21) elicits an array of metabolic effects. However, the physiological role FGF21 during thermal challenges is not clear. In this study, we assessed tissue source and its site action to regulate core body temperature in response cold. Using mice lacking specifically liver (FGF21 LivKO) or adipose tissues AdipoKO), performed a series cold exposure studies examine specific induction We also examined by impairing signaling central nervous system (CNS) using...
Fibroblast growth factor 21 (FGF21) is an endocrine hormone that regulates metabolic homeostasis. Previous work has suggested impairment of FGF21 signaling in adipose tissue may occur through downregulation the obligate co-receptor, β-klotho, which leads to "FGF21 resistance" during onset diet-induced obesity. Here, we sought determine whether maintenance β-klotho expression prevents resistance and other mechanisms also contribute vivo. We generated adipose-specific transgenic mice protein...
<ns4:p>The term “FGF21 resistance” was first used to describe increased circulating FGF21 levels concomitant decreased receptor complex expression in white adipose tissue of obese mice. Since this initial report, the has been associated with a wide range pathological states, including human obesity, which are elevated. However, notion controversial partly due difficulty delineating mechanisms underlying physiological versus pharmacological effects FGF21. Here, key aspects discussed...
Hypercholesterolemia is found in patients with hypothyroidism and resistance to thyroid hormone. In this study, we examined cholesterol metabolism a hormone receptor beta (TR-beta) mutant mouse model of Whereas studies have been reported TR-beta knock-out mice, generalized expression non-ligand binding protein knock-in more fully recapitulates the hypothyroid state, because effect TRs mediated by unliganded receptor. high diet increased serum levels wild-type animals (WT) but either did not...
Activation of the brain renin-angiotensin system (RAS) stimulates energy expenditure through increasing resting metabolic rate (RMR), and this effect requires simultaneous suppression circulating and/or adipose RAS. To identify mechanism by which peripheral RAS opposes RMR control RAS, we examined mice with transgenic activation (sRA mice). sRA exhibit increased flux in inguinal tissue, is attenuated angiotensin II type 2 receptor (AT2) activation. AT2 adipocytes norepinephrine-induced...
T-box 1 (TBX1) has been identified as a genetic marker of beige adipose tissue. TBX1 is mesodermal development transcription factor essential for tissue patterning and cell fate determination. However, whether it plays role in the process beiging or how functions not reported. Here, we examined function well adipose-derived stem cells from mice humans.
Aryl hydrocarbon receptor (AHR) agonists such as dioxin have been associated with obesity and the development of diabetes. Whole-body Ahr knockout mice on high-fat diet (HFD) shown to resist hepatic steatosis. Tissue-specific in mature adipocytes via adiponectin-Cre exacerbates while liver increases steatosis without having significant effects obesity. Our previous studies demonstrated that treatment subcutaneous preadipocytes exogenous or endogenous AHR disrupts maturation into functional...
Adipose tissue is a primary site for lipid storage containing trace amounts of glycogen. However, refeeding after prolonged partial fast produces marked transient spike in adipose glycogen, which dissipates coordination with the initiation resynthesis. To further study potential interplay between glycogen and metabolism tissue, aP2-PTG transgenic mouse line was utilized since it contains 100- to 400-fold elevation adipocyte levels that are mobilized upon fasting. determine fate released...
Abstract Obesity, which impacts 36% of adults in the U.S., is associated with an increased risk ER-positive breast cancer postmenopausal women, incidence more aggressive triple negative cancer, developing invasive ductal carcinoma (IDC) versus situ (DCIS; non-invasive) and a worse clinical outcome. There have been many hypotheses to explain this link between obesity but causal mechanism still largely missing. Here, using two syngeneic orthotopic transplant models C57Bl/6 mice, we examined...
Transgenic “sRA” mice with brain renin‐angiotensin system hyperactivity express human renin via the synapsin promoter and angiotensinogen its own promoter. These exhibit an elevated resting metabolic rate (RMR) that is normalized by replacement of circulating angiotensin II (ANG), but thermogenic tissue ANG receptors involved are unknown. sRA exhibited a robust specific elevation in uncoupling protein 1 (UCP1) expression glucose uptake inguinal adipose tissue. Chronic infusion AT 2 receptor...
The renin-angiotensin system (RAS) positively correlates with obesity, and contributes to energy homeostasis through opposing actions in the brain adipose. We hypothesize that site- receptor-specific modulation may represent a novel therapeutic target for obesity. Transgenic “sRA” mice exhibit brain-specific RAS hyperactivity expression of human renin neurons (synapsin promoter) angiotensinogen via its own promoter. Previously we documented sRA suppressed circulating RAS, an elevated resting...
Exercise training improves whole body glucose homeostasis, effects largely attributed to adaptations skeletal muscle; however, also affects other tissues including adipose tissue. We used a transplantation model test the hypothesis that tissue contribute training‐induced improvements in homeostasis. Mice were trained for 11 days or sedentary, and subcutaneous (SubQ) visceral was transplanted into cavity of sedentary recipients. Nine after transplant, mice receiving SubQ from had improved...
Circadian misalignment—sleeping during the biological day and eating at a time when internal circadian clock promotes sleep—is risk factor for obesity diabetes, implicating misalignment as metabolic stressor. Fibroblast growth 21 (FGF-21) is hepatokine secreted in response to stress found be elevated human diabetes. Activation of peroxisome proliferator-activator receptor alpha by free fatty acids (FFA), can induce expression FGF-21 expression. It has been previously reported that results...