A5002153983- Adipose Tissue and Metabolism
- Thyroid Disorders and Treatments
- Adipokines, Inflammation, and Metabolic Diseases
- Growth Hormone and Insulin-like Growth Factors
- Diet and metabolism studies
- Cancer, Hypoxia, and Metabolism
- Regulation of Appetite and Obesity
- Muscle metabolism and nutrition
- Advancements in Transdermal Drug Delivery
- Lipid Membrane Structure and Behavior
- Mitochondrial Function and Pathology
- Thermoregulation and physiological responses
- Cholesterol and Lipid Metabolism
- Genetics and Neurodevelopmental Disorders
- Estrogen and related hormone effects
- Cardiovascular Disease and Adiposity
- Virus-based gene therapy research
- Lipid metabolism and biosynthesis
- Neuroscience of respiration and sleep
- Retinoids in leukemia and cellular processes
- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- Migration, Racism, and Human Rights
- Microbial Inactivation Methods
- Hypothalamic control of reproductive hormones
Universidade Federal do ABC
2012-2023
Centro Regional de Derechos Humanos y Justicia de Género, Corporación Humanas
2021
Centro Universitário Fundação Santo André
2021
Universidade de São Paulo
2000-2015
Harvard University Press
2005-2010
Semmelweis University
2010
Hungarian Academy of Sciences
2010
Brigham and Women's Hospital
2004-2007
Harvard University
2004-2007
TD Bank
2006
Hormone-sensitive lipase (HSL) is the predominant effector of catecholamine-stimulated lipolysis in adipocytes. HSL-dependent response to catecholamines mediated by protein kinase A (PKA)-dependent phosphorylation perilipin (Peri A), an essential lipid droplet (LD)-associated protein. It believed that for translocation HSL from cytosol LD, a key event stimulated lipolysis. Using adipocytes retrovirally engineered murine embryonic fibroblasts null mice (Peri-/- MEF), we demonstrate cell...
The Dio2 gene encodes the type 2 deiodinase (D2) that activates thyroxine (T4) to 3,3′,5-triiodothyronine (T3), disruption of which (Dio2−/−) results in brown adipose tissue (BAT)-specific hypothyroidism an otherwise euthyroid animal. In present studies, cold exposure increased Dio2−/− BAT sympathetic stimulation ∼10-fold (normal ∼4-fold); as a result, lipolysis, well mRNA levels uncoupling protein 1, guanosine monophosphate reductase, and peroxisome proliferator–activated receptor γ...
Disturbances in energy homeostasis can result obesity and other metabolic diseases. Here we report a pathway present normal human skeletal muscle myoblasts that is activated by the small polyphenolic molecule kaempferol (KPF). Treatment with KPF leads to an ∼30% increase myocyte oxygen consumption. The mechanism involves several-fold cyclic AMP (cAMP) generation protein kinase A activation, effect of be mimicked via treatment dibutyryl cAMP. Microarray real-time PCR studies identified set...
Mice with one thyroid hormone receptor (TR) α-1 allele encoding a dominant negative mutant (TRα1PV/+) have persistently elevated serum T3 levels (1.9-fold above normal). They also markedly increased hepatic type 1 iodothyronine deiodinase (D1) mRNA and enzyme activity (4- to 5-fold), whereas other T3-responsive genes, such as Spot14 mitochondrial α-glycerol phosphate dehydrogenase (α-GPD), are only 0.7-fold 1.7-fold that of wild-type littermates (TRα1+/+). To determine the cause...
T(4), the main product of thyroid secretion, is a critical signal in plasma that mediates TSH-negative feedback mechanism. As prohormone, T(4) must be converted to T(3) acquire biological activity; thus, type 2 iodothyronine deiodinase (D2) expected play role this However, mechanistic details pathway are still missing because, counterintuitively, D2 activity rapidly lost presence by ubiquitin-proteasomal In present study, we demonstrate and TSH coexpressed rat pituitary thyrotrophs...
Type 2 deiodinase (D2), which is highly expressed in brown adipose tissue (BAT), an enzyme that amplifies thyroid hormone signaling individual cells. Mice with inactivation of the D2 pathway (D2KO) exhibit dramatically impaired thermogenesis BAT, leading to hypothermia during cold exposure and a greater susceptibility diet-induced obesity. This was interpreted as result defective acute activation BAT D2. Here we report adult D2KO has permanent thermogenic defect stems from embryonic...
Brown adipose tissue (BAT) is predominantly regulated by the sympathetic nervous system (SNS) and adrenergic receptor signaling pathway. Knowing that a mouse with triple β-receptor knockout (KO) cold intolerant obese, we evaluated independent role played β 1 isoform in energy homeostasis. First, 30 min i.v. infusion of norepinephrine (NE) or selective agonist dobutamine (DB) resulted similar interscapular BAT (iBAT) thermal response WT mice. Secondly, mice targeted disruption gene (KO (β...
The reductions in circulating levels of leptin, insulin, and glucose with fasting serve as important homeostasis signals to neurons the hypothalamic arcuate nucleus that synthesize neuropeptide Y (NPY)/agouti-related protein (AGRP) alpha-MSH/cocaine amphetamine-regulated transcript. Because central administration leptin is capable preventing inhibitory effects on TRH mRNA hypophysiotropic primarily through nucleus, we determined whether continuous 30 mU/d insulin or 648 microg/d into...
Thyroid hormone affects multiple aspects of bone metabolism, but little is known about thyroid deiodination in cells except that cultures skeletal and organ express types 1 2 iodothyronine deiodinases (D1 D2) mRNAs. In the present study, outer ring (ORD) activity was detected extracts sites mouse skeleton, marrow, MC3T3-E1 osteoblastic cell line. all tissues, ORD using 125I-rT3 or 125I-T4 as substrates found to be 6-n-propylthiouracil insensitive, display a Michaelis constant (T4)...
For T3 to mediate its biological effects, the prohormone T4 must be activated by removal of an outer-ring iodine type 1 or 2 deiodinases (D1 and D2) with approximately 60% daily production in rodents being produced extrathyroidally through this pathway. To further define role these enzymes thyroid hormone homeostasis, we backcrossed targeted disruption Dio2 gene into C3H/HeJ (C3H) mice genetically low D1 expression create C3H-D2KO mouse. Remarkably, maintain euthyroid serum levels normal...
Thyroid hormone receptor β (TRβ also listed as THRB on the MGI Database)-selective agonists activate brown adipose tissue (BAT) thermogenesis, while only minimally affecting cardiac activity or lean body mass. Here, we tested hypothesis that daily administration of TRβ agonist GC-24 prevents metabolic alterations associated with a hypercaloric diet. Rats were placed high-fat diet and after month exhibited increased weight (BW) adiposity, fasting hyperglycemia glucose intolerance, plasma...
Three types of beta adrenergic receptors (ARβ1-3) mediate the sympathetic activation brown adipose tissue (BAT), key thermogenic site for mice which is also present in adult humans. In this study, we evaluated adaptive thermogenesis and metabolic profile a mouse with Arβ2 knockout (ARβ2KO). At room temperature, ARβ2KO have normal core temperature and, upon acute cold exposure (4 °C 4 h), accelerate energy expenditure normally attempt to maintain body temperature. exhibited interscapular BAT...
To study the thermal response of interscapular brown fat (IBF) to norepinephrine (NE), urethan-anesthetized rats (1.2 g/kg ip) maintained at 28–30°C received a constant venous infusion NE (0–2 × 10 4 pmol/min) over period 60 min. IBF temperatures (T ) were recorded with small thermistor fixed under pad. Data plotted against time and expressed as maximal variation (Δ t°C). Saline-injected showed decrease in T ∼0.6°C. increased by maximum ∼3.0°C dose pmol · min −1 100 g body wt . Surgically...
Thyroid hormone receptor (TR) and liver X-receptor (LXR) are the master regulators of lipid metabolism. Remarkably, a mouse with targeted deletion both LXR alpha beta is resistant to western diet-induced obesity, exhibits ectopic expression thyroid activating type 2 deiodinase (D2). We hypothesized that LXR/retinoid (RXR) signaling inhibits hepatic D2 expression, studied this using luciferase reporter containing human DIO2 (hDIO2) promoter in HepG2 cells. Given that, contrast mammals,...
C57Bl/6J mice are the gold standard animal model of diet-induced obesity. These animals become obese with higher adiposity, blood fasting glucose, triglycerides, and total cholesterol when fed a high-fat diet (HFD). Conversely, FVB/N mouse line is thought to be resistant obesity, low or no weight gain adiposity in response HFD. In this study, we investigated whether susceptible metabolic disorder that promoted by Biometric parameters chemistry were analyzed chow Glucose insulin sensitivity...
This investigation highlights that ocular and hepatic gene delivery can be potentialized by using small hydrophobic moieties along with lactose domains, principally, succinic acid conjugated to polyethylenimine chains.
CD44 is an adhesion molecule in the extracellular matrix that shows various functions, including tumor genesis and metastasis. A recent study showed expression level was strongly correlated with generation of papillary thyroid carcinomas, most prevalent malignancy gland. We report here negatively regulated by hormone (T<sub>3</sub>) through a novel mechanism. demonstrate nuclear receptor corepressor (NCoR) enhances (TR)-mediated basal transactivation weak TR·DNA interaction absence...
The type 2 deiodinase (D2) activates thyroid hormone and constitutes an important source of 3,5,3',-triiodothyronine in the brain. D2 is inactivated via WSB-1 mediated ubiquitination but can be rescued from proteasomal degradation by USP-33 deubiquitination. Using silico analysis published array data, we found a significant positive correlation between relative mRNA expression levels set 56 mouse tissues (r = 0.08; P < 0.04). Subsequently, used situ hybridization combined with...