A5073718834- Thyroid Disorders and Treatments
- Adipose Tissue and Metabolism
- Liver Disease Diagnosis and Treatment
- Diet and metabolism studies
- Mitochondrial Function and Pathology
- Growth Hormone and Insulin-like Growth Factors
- Diet, Metabolism, and Disease
- Adipokines, Inflammation, and Metabolic Diseases
- Epigenetics and DNA Methylation
- Natural Antidiabetic Agents Studies
- Birth, Development, and Health
- Phytochemicals and Antioxidant Activities
- Lipid metabolism and biosynthesis
- Pancreatic function and diabetes
- Thyroid Cancer Diagnosis and Treatment
- Genetics and Neurodevelopmental Disorders
- Electrolyte and hormonal disorders
- FOXO transcription factor regulation
- Insect Pest Control Strategies
- Renal and related cancers
- Endoplasmic Reticulum Stress and Disease
- Exercise and Physiological Responses
- Bee Products Chemical Analysis
- Renal function and acid-base balance
- Muscle Physiology and Disorders
University of Chicago
2018-2021
University of Illinois Chicago
2020
University of Chicago Medical Center
2019
Rush University Medical Center
2015-2018
Universidade Federal de São Paulo
2015-2018
Universidade Presbiteriana Mackenzie
2012-2016
University of Miami
2014
Fundação de Apoio à Universidade Federal de São Paulo
2012-2013
Levothyroxine (LT4) is a form of thyroid hormone used to treat hypothyroidism. In the brain, T4 converted active T3 by type 2 deiodinase (D2). Thus, it intriguing that carriers Thr92Ala polymorphism in D2 gene (DIO2) exhibit clinical improvement when liothyronine (LT3) added LT4 therapy. Here, we report cargo protein ER Golgi intermediary compartment (ERGIC) vesicles, recycling between and Golgi. The Thr92-to-Ala substitution (Ala92-D2) caused stress activated unfolded response (UPR)....
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...
Type 2 deiodinase (D2) converts the prohormone thyroxine (T4) to metabolically active molecule 3,5,3'-triiodothyronine (T3), but its global inactivation unexpectedly lowers respiratory exchange rate (respiratory quotient [RQ]) and decreases food intake. Here we used FloxD2 mice generate systemically euthyroid fat-specific (FAT), astrocyte-specific (ASTRO), or skeletal-muscle-specific (SKM) D2 knockout (D2KO) that were monitored continuously. The ASTRO-D2KO also exhibited lower diurnal RQ...
Millions of levothyroxine-treated hypothyroid patients complain impaired cognition despite normal TSH serum levels. This could reflect abnormalities in the type 2 deiodinase (D2)-mediated T4-to-T3 conversion, given their much greater dependence on D2 pathway for T3 production. normally reaches brain directly from circulation or is produced locally by astrocytes. Here we report that mice with astrocyte-specific Dio2 inactivation (Astro-D2KO) have but exhibit anxiety-depression-like behavior...
Iodothyronine deiodinase-1 (D1) selenoenzyme regulates the systemic supply of active thyroid hormone (TH). Transient decrease in D1 enzymatic activity is clinically relevant and adaptive nonthyroidal illness such as fasting or acute illness. However,
Significance Thyroid hormone is secreted mostly as a prohormone that must be activated to gain biological activity. The activation reaction the removal of one iodine atom, i.e., deiodination thyroxine active thyroid triiodothyronine (T3), which catalyzed by group enzymes known deiodinases. These control amounts intracellular and circulating T3. Here we report in mice, there brief neonatal surge hepatocyte type 2 deiodinase (D2) transiently stimulates liver expression lipid-related genes. D2...
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...
Abstract The type 2 deiodinase (D2) in the neonatal liver accelerates local thyroid hormone triiodothyronine (T3) production and expression of T3-responsive genes. Here we show that this surge T3 permanently modifies hepatic gene expression. Liver-specific Dio2 inactivation (Alb-D2KO) transiently increases H3K9me3 levels during post-natal days 1–5 (P1–P5), results methylation 1,508 DNA sites (H-sites) adult mouse liver. These are associated with 1,551 areas reduced chromatin accessibility...
The type 2 deiodinase (D2) activates the prohormone T4 to T3. D2 is expressed in skeletal muscle (SKM), and its global inactivation (GLOB-D2KO mice) reportedly leads hypothyroidism impaired differentiation. Here floxed Dio2 mice were crossed with expressing Cre-recombinase under myosin light chain 1f (cre-MLC) disrupt expression late developmental stages of myocytes (SKM-D2KO). This led a loss approximately 50% activity neonatal adult SKM-D2KO about 75% isolated myocytes. To test impact...
Fractionation of the EtOH extract from aerial parts Baccharis uncinella C. DC. (Asteraceae) led to isolation caffeic and ferulic acids, which were identified spectroscopic spectrometric evidence. These compounds exhibit antioxidant anti-inflammatory properties have been shown be effective in prevention/treatment metabolic syndrome. This study investigated whether combined treatment acids exhibits a more significant beneficial effect mouse model with The combination was tested for 60 days C57...
Liver-specific disruption of the type 2 deiodinase gene (Alb-D2KO) results in resistance to both diet-induced obesity and liver steatosis mice. Here, we report that this is explained by an ∼60% reduction zinc-finger protein-125 (Zfp125) expression. Zfp125 a Foxo1-inducible transcriptional repressor causes lipid accumulation AML12 mouse hepatic cell line mice reducing secretion triglycerides hepatocyte efflux cholesterol. acts repressing 18 genes involved lipoprotein structure, binding,...
Liothyronine (LT3) has limited short-term clinical applications, all of which aim at suppressing thyrotropin (TSH) secretion. A more controversial application is chronic administration along with levothyroxine in the treatment hypothyroidism. Long-term LT3 complicated by its unique pharmacokinetics that result a substantial triiodothyronine (T3) peak blood three to four hours after oral dosing. This significant problem, given T3 levels are normally stable, varying <10% throughout day.A metal...
Abstract Introduction The inflammatory response of critical illness is accompanied by nonthyroidal syndrome (NTIS). Feeding has been shown to attenuate this process, but not explored prospectively over time in critically ill patients. Objective To explore the impact calorie exposure on NTIS Methods Mechanically ventilated patients with systemic (SIRS) were randomized receive either 100% or 40% their estimated caloric needs (ECN). Thyroid hormones measured daily for 7 days until intensive...
Background A mouse with hepatocyte‐specific deiodinase type II inactivation (Alb‐D2 KO ) is resistant to diet‐induced obesity, hepatic steatosis, and hypertriglyceridemia due perinatal epigenetic modifications in the liver. This phenotype linked low levels of Zfp125, a transcriptional repressor that promotes liver steatosis by inhibiting genes involved packaging secretion very‐low‐density lipoprotein. Methods Here, we used chronic binge ethanol ( EtOH mice cause steatosis. Results The...
Abstract To study thyroid hormone (TH) signaling in the human brain, we analyzed published microarray data sets of temporal pole (Brodmann area 38) 19 deceased donors. An index TH built on expression well known TH-responsive genes mouse brains (T3S+) varied from 0.92 to 1.1. After Factor analysis, T3S+ correlated independently with transporters (MCT8, LAT2), receptor (TR) beta and TR coregulators (CARM1, MED1, KAT2B, SRC2, SRC3, NCOR2a). Unexpectedly, no correlation was found between vs...
Abstract More than a billion people worldwide are at risk of iodine deficiency (ID), with well-known consequences for development the central nervous system. Furthermore, ID has also been associated dyslipidemia and obesity in humans. To further understand metabolic ID, here we kept 8-week-old C57/Bl6 mice thermoneutrality (~28°C) while feeding them on low diet (LID). When compared control (LID + 0.71 μg/g iodine), LID exhibited marked reduction T4 elevated plasma TSH, without changes T3...
Status epilepticus (SE) is an abnormally prolonged seizure that results from either a failure of mechanisms terminate seizures or initiating inherently lead to seizures. Here we report mice experiencing 3 hours SE caused by pilocarpine exhibit rapid increase in expression type 2 iodothyronine deiodinase gene (Dio2) and decrease the hippocampus, amygdala prefrontal cortex. Type hippocampal sections was seen concentrated neuronal nuclei, typical ischemic injury brain. An unbiased analysis...
In the print version of article listed above, correct name author as Alexandre Ferreira is Alexander R. Ferreira. The online reflects this change.
Abstract Iodothyronine deiodinases (Ds) mediate thyroid hormone (TH) action. They catalyze triiodothyronine (T3) production and degradation via, respectively; outer (ORD) inner (IRD) ring deiodination. Type 1 D (D1) has a relatively high Km for substrates thyroxine (T4) reverse T3 (rT3), catalyzes both ORD IRD is inhibited by propylthiouracil (PTU). Although no mutations in DIO1 gene have been reported so far humans, based on the D1-deficient C3H mouse heterozygous Dio1 knockout mice,...
Summary Zfp125 is a transcriptional repressor that inhibits hepatic VLDL secretion. Here we show mice with liver-specific knockdown exhibited lower respiratory quotient, reduced glycemia and pyruvate-stimulated liver glucose output, higher levels of β-hydroxyl-butyrate. Microarray ChIP-seq studies identified peaks in the promoter 135 metabolically relevant genes, including genes involved fatty acid oxidation ketogenesis, e.g. Ppara, Cpt1a, Bdh1 Hmgcs2. Repression by recruitment corepressors...
Several studies have been shown that Caffeic Acid (CA) and Ferulic (FA) present antioxidant anti‐inflammatory properties improve several abnormalities related to metabolic syndrome. The aim of this study was analyze the effect CA FA combined on diet induced obesity in mice. For that, C57 mice fed with high fat (HFD) (40%) received plus concomitantly for 60 days. Our results showed combination (0.9 or 1.8 mg/kg/day) (50 reduced body weight gain by HFD (8.6±1.8 vs. −4.2±2.0 (CA0.9+FA50)...
In the neonatal liver, a peak of type 2 deiodinase (D2) activity accelerates local T3 production and expression thyroid hormone (TH)-responsive genes. Here we show that this acute increase in signaling permanently modifies hepatic gene expression. Liver-specific Dio2 inactivation (Alb-D2KO) transiently increased H3K9me3 levels during post-natal days 1-5 (P1-P5) discrete chromatin areas, methylation 1,508 DNA sites (H-sites) remained adult mouse liver. These were associated with 1,551 areas...