Platelet bioenergetic profiling uncovers a metabolic pattern of high dependency on mitochondrial fatty acid oxidation in type 2 diabetic patients who developed in-stent restenosis.

Although platelet bioenergetic dysfunction is evident early in the pathogenesis of diabetic macrovascular complications, the bioenergetic characteristics in type 2 diabetic patients who developed coronary in-stent restenosis (ISR) and their effects on platelet function remain unclear. Here, we performed platelet bioenergetic profiling to characterize the bioenergetic alterations in 28 type 2 diabetic patients with ISR compared with 28 type 2 diabetic patients without ISR (non-ISR) and 28 healthy individuals. Generally, platelets from type 2 diabetic patients with ISR exhibited a specific bioenergetic alteration characterized by high dependency on fatty acid (FA) oxidation, which subsequently induced complex III deficiency, causing decreased mitochondrial respiration, increased mitochondrial oxidant production, and low efficiency of mitochondrial ATP generation. This pattern of bioenergetic dysfunction showed close relationships with both α-granule and dense granule secretion as measured by surface P-selectin expression, ATP release, and profiles of granule cargo proteins in platelet releasates. Importantly, ex vivo reproduction of high dependency on FA oxidation by exposing non-ISR platelets to its agonist mimicked the bioenergetic dysfunction observed in ISR platelets and enhanced platelet secretion, whereas pharmaceutical inhibition of FA oxidation normalized the respiratory and redox states of ISR platelets and diminished platelet secretion. Further, causal mediation analyses identified a strong association between high dependency on FA oxidation and increased angiographical severity of ISR, which was significantly mediated by the status of platelet secretion. Our findings, for the first time, uncover a pattern of bioenergetic dysfunction in ISR and enhance current understanding of the mechanistic link of high dependency on FA oxidation to platelet abnormalities in the context of diabetes.

Walking around the preferred speed: examination of metabolic, perceptual, spatiotemporal and stability parameters.

Walking is the most accessible and common type of physical activity. Exercising at one's self-selected intensity could provide long-term benefits as compared to following prescribed intensities. The aim of this study was to simultaneously examine metabolic, perceptual, spatiotemporal and stability parameters at an absolute 3 km·h-1 speed range around the individual preferred walking speed (PWS). Thirty-four young sedentary adults (18 women) volunteered to walk at seven speeds relative to their PWS in 3-min trials interspaced with 3-min rest intervals. Results indicated a significant main effect of speed on all studied variables. While metabolic, perceptual and spatiotemporal values were sensitive to the smallest change in speed (i.e., 0.5 km·h-1), a significant increase in the rate of carbohydrate oxidation and decrease in %fat oxidation were only observed at speeds above PWS. Results also revealed significantly higher coefficients of variation for stride characteristics at speeds below PWS only. Moreover, analyses of best fit models showed a quadratic relationship between most variables and speed, with the exceptions of metabolic cost of transport, rating of perceived exertion and stride duration that changed exponentially with speed. PWS coincided with optimized mechanical efficiency, fuel oxidation and gait stability. This indicated that walking below PWS decreased both mechanical efficiency and stability of gait, while walking above PWS increased carbohydrate oxidation. Those factors seem to play an important role as determinants of PWS. We suggest that walking at PWS may provide benefits in terms of fat oxidation while optimizing gait stability.

Resting energy metabolism and sweet taste preference during the menstrual cycle in healthy women.

Differences in blood concentration of sex hormones in the follicular (FP) and luteal (LP) phases may influence energy metabolism in women. We compared fasting energy metabolism and sweet taste preference on a representative day of the FP and LP in twenty healthy women (25·3 (sd 5·1) years, BMI: 22·2 (sd 2·2) kg/m2) with regular self-reported menses and without the use of hormonal contraceptives. From the self-reported duration of the three prior menstrual cycles, the predicted FP and LP visits were scheduled for days 5-12 and 20-25 after menses, respectively. The order of the FP and LP visits was randomly assigned. On each visit, RMR and RQ by indirect calorimetry, sweet taste preference by the Monell two-series forced-choice tracking procedure, serum fibroblast growth factor 21 by a commercial ELISA (FGF21, a liver-derived protein with action in energy balance, fuel oxidation and sugar preference) and dietary food intake by a 24-h dietary recall were determined. Serum progesterone and oestradiol concentrations displayed the expected differences between phases. RMR was lower in the FP v. LP (5042 (sd 460) v. 5197 (sd 490) kJ/d, respectively; P = 0·04; Cohen effect size, d rm = 0·33), while RQ showed borderline significant higher values (0·84 (sd 0·05) v. 0·81 (sd 0·05), respectively; P = 0·07; d rm = 0·62). Also, in the FP v. LP, sweet taste preference was lower (12 (sd 8) v. 16 (sd 9) %; P = 0·04; d rm = 0·47) concomitant with higher serum FGF21 concentration (294 (sd 164) v. 197 (sd 104) pg/ml; P < 0·01; d rm = 0·66). The menstrual cycle is associated with changes in energy expenditure, sweet taste preference and oxidative fuel partitioning.

Synthetic NAD(P)(H) Cycle for ATP Regeneration.

ATP is the energy currency of the cell and new methods for ATP regeneration will benefit a range of emerging biotechnology applications including synthetic cells. We designed and assembled a membraneless ATP-regenerating enzymatic cascade by exploiting the substrate specificities of selected NAD(P)(H)-dependent oxidoreductases combined with substrate-specific kinases. The enzymes in the NAD(P)(H) cycle were selected to avoid cross-reactions, and the cascade was driven by irreversible fuel oxidation. As a proof-of-concept, formate oxidation was chosen as the fueling reaction. ATP regeneration was accomplished via the phosphorylation of NADH to NADPH and the subsequent transfer of the phosphate to ADP by a reversible NAD+ kinase. The cascade was able to regenerate ATP at a high rate (up to 0.74 mmol/L/h) for hours, and >90% conversion of ADP to ATP using monophosphate was also demonstrated. The cascade was used to regenerate ATP for use in cell free protein synthesis reactions, and the ATP production rate was further enhanced when powered by the multistep oxidation of methanol. The NAD(P)(H) cycle provides a simple cascade for the in vitro regeneration of ATP without the need for a pH-gradient or costly phosphate donors.

Human adaptation to immobilization: Novel insights of impacts on glucose disposal and fuel utilization.

BACKGROUND: Bed rest (BR) reduces whole-body insulin-stimulated glucose disposal (GD) and alters muscle fuel metabolism, but little is known about metabolic adaptation from acute to chronic BR nor the mechanisms involved, particularly when volunteers are maintained in energy balance. METHODS: Healthy males (n = 10, 24.0 ± 1.3 years), maintained in energy balance, underwent 3-day BR (acute BR). A second cohort matched for sex and body mass index (n = 20, 34.2 ± 1.8 years) underwent 56-day BR (chronic BR). A hyperinsulinaemic euglycaemic clamp (60 mU/m2 /min) was performed to determine rates of whole-body insulin-stimulated GD before and after BR (normalized to lean body mass). Indirect calorimetry was performed before and during steady state of each clamp to calculate rates of whole-body fuel oxidation. Muscle biopsies were taken to determine muscle glycogen, metabolite and intramyocellular lipid (IMCL) contents, and the expression of 191 mRNA targets before and after BR. Two-way repeated measures analysis of variance was used to detect differences in endpoint measures. RESULTS: Acute BR reduced insulin-mediated GD (Pre 11.5 ± 0.7 vs. Post 9.3 ± 0.6 mg/kg/min, P < 0.001), which was unchanged in magnitude following chronic BR (Pre 10.2 ± 0.4 vs. Post 7.9 ± 0.3 mg/kg/min, P < 0.05). This reduction in GD was paralleled by the elimination of the 35% increase in insulin-stimulated muscle glycogen storage following both acute and chronic BR. Acute BR had no impact on insulin-stimulated carbohydrate (CHO; Pre 3.69 ± 0.39 vs. Post 4.34 ± 0.22 mg/kg/min) and lipid (Pre 1.13 ± 0.14 vs. Post 0.59 ± 0.11 mg/kg/min) oxidation, but chronic BR reduced CHO oxidation (Pre 3.34 ± 0.18 vs. Post 2.72 ± 0.13 mg/kg/min, P < 0.05) and blunted the magnitude of insulin-mediated inhibition of lipid oxidation (Pre 0.60 ± 0.07 vs. Post 0.85 ± 0.06 mg/kg/min, P < 0.05). Neither acute nor chronic BR increased muscle IMCL content. Plentiful mRNA abundance changes were detected following acute BR, which waned following chronic BR and reflected changes in fuel oxidation and muscle glycogen storage at this time point. CONCLUSIONS: Acute BR suppressed insulin-stimulated GD and storage, but the extent of this suppression increased no further in chronic BR. However, insulin-mediated inhibition of fat oxidation after chronic BR was less than acute BR and was accompanied by blunted CHO oxidation. The juxtaposition of these responses shows that the regulation of GD and storage can be dissociated from substrate oxidation. Additionally, the shift in substrate oxidation after chronic BR was not explained by IMCL accumulation but reflected by muscle mRNA and pyruvate dehydrogenase kinase 4 protein abundance changes, pointing to lack of muscle contraction per se as the primary signal for muscle adaptation.

Uncertain association between maximal fat oxidation during exercise and cardiometabolic risk factors in healthy sedentary adults.

The present work examines the relationships between maximal fat oxidation during a graded exercise test (MFO), the intensity of exercise that elicits MFO (Fatmax), and traditional cardiometabolic risk factors in healthy, sedentary adults. A total of 119 (81 women) young, sedentary adults (22.1 ± 2.2 years old), and 71 (37 women) middle-aged, sedentary adults (53.4 ± 4.9 years old) participated in the current study. Systolic and diastolic blood pressures were determined following standard procedures. Plasma glucose, insulin, total cholesterol, high-density lipoprotein cholesterol and triglycerides were determined in a fasted state and the homeostatic model assessment of insulin resistance index and low-density lipoprotein cholesterol levels subsequently calculated. A sex and age group-specific cardiometabolic risk Z-score was also calculated for each subject based on waist circumference, systolic and diastolic blood pressure, plasma glucose, high-density lipoprotein cholesterol and triglycerides. MFO and Fatmax were determined using a walking graded exercise test using indirect calorimetry. No clear association was seen of MFO and Fatmax with any cardiometabolic risk factor (all P≥0.05), except for a weak, inverse association between Fatmax and the fatty liver index (P=0.027). Similarly, neither MFO nor Fatmax was apparently associated with the cardiometabolic risk Z-score (all P≥0.05). The current findings suggest an uncertain association of MFO and Fatmax during a graded exercise test with the cardiometabolic profile of healthy, sedentary adults.HighlightsThe study of the physiological mechanisms that trigger the onset of metabolic disorders has received considerable attention in recent years, with changes in MFO and Fatmax being highlighted as a potential key factor.This work shows that MFO and Fatmax during a graded exercise test are not associated with the cardiometabolic profile in sedentary, healthy adults.Further studies are needed to elucidate which other physiological disorders are related to cardiometabolic risk.

Association Between Adipose Tissue Characteristics and Metabolic Flexibility in Humans: A Systematic Review.

Adipose tissue total amount, distribution, and phenotype influence metabolic health. This may be partially mediated by the metabolic effects that these adipose tissue characteristics exert on the nearby and distant tissues. Thus, adipose tissue may influence the capacity of cells, tissues, and the organism to adapt fuel oxidation to fuel availability, i.e., their metabolic flexibility (MetF). Our aim was to systematically review the evidence for an association between adipose tissue characteristics and MetF in response to metabolic challenges in human adults. We searched in PubMed (last search on September 4, 2021) for reports that measured adipose tissue characteristics (total amount, distribution, and phenotype) and MetF in response to metabolic challenges (as a change in respiratory quotient) in humans aged 18 to <65 years. Any study design was considered, and the risk of bias was assessed with a checklist for randomized and non-randomized studies. From 880 records identified, 22 remained for the analysis, 10 of them measured MetF in response to glucose plus insulin stimulation, nine in response to dietary challenges, and four in response to other challenges. Our main findings were that: (a) MetF to glucose plus insulin stimulation seems inversely associated with adipose tissue total amount, waist circumference, and visceral adipose tissue; and (b) MetF to dietary challenges does not seem associated with adipose tissue total amount or distribution. In conclusion, evidence suggests that adipose tissue may directly or indirectly influence MetF to glucose plus insulin stimulation, an effect probably explained by skeletal muscle insulin sensitivity. Systematic Review Registration: PROSPERO [CRD42020167810].

Recent Progress of Ultrathin 2D Pd-Based Nanomaterials for Fuel Cell Electrocatalysis.

Pd- and Pd-based catalysts have emerged as potential alternatives to Pt- and Pt-based catalysts for numerous electrocatalytic reactions, particularly fuel cell-related reactions, including the anodic fuel oxidation reaction (FOR) and cathodic oxygen reduction reaction (ORR). The creation of Pd- and Pd-based architectures with large surface areas, numerous low-coordinated atoms, and high density of defects and edges is the most promising strategy for improving the electrocatalytic performance of fuel cells. Recently, 2D Pd-based nanomaterials with single or few atom thickness have attracted increasing interest as potential candidates for both the ORR and FOR, owing to their remarkable advantages, including high intrinsic activity, high electron mobility, and straightforward surface functionalization. In this review, the recent advances in 2D Pd-based nanomaterials for the FOR and ORR are summarized. A fundamental understanding of the FOR and ORR is elaborated. Subsequently, the advantages and latest advances in 2D Pd-based nanomaterials for the FOR and ORR are scientifically and systematically summarized. A systematic discussion of the synthesis methods is also included which should guide researchers toward more efficient 2D Pd-based electrocatalysts. Lastly, the future outlook and trends in the development of 2D Pd-based nanomaterials toward fuel cell development are also presented.

Association of sedentary and physical activity time with maximal fat oxidation during exercise in sedentary adults.

The present work examines the relationships of objectively measured sedentary time and physical activity (PA) with maximal fat oxidation during exercise (MFO) and the intensity of exercise that elicits MFO (Fatmax ), in young and middle-aged men and women. A total of 121 young sedentary adults (81 women, age 22.1 ± 2.1 years, body mass index 25.2 ± 4.9 kg/m2 ) and 70 middle-aged sedentary adults (36 women, age 53.4 ± 4.9 years, body mass index 26.8 ± 3.8 kg/m2 ) participated in this cross-sectional study. PA was objectively assessed using a wrist-worn accelerometer for 7 consecutive days. Wrist accelerations were classified into sedentary time and PA of different intensity (light, moderate, vigorous, moderate-vigorous), taking into account age-specific cut-offs. MFO and Fatmax were determined for all subjects by indirect calorimetry, using a walking graded exercise test. No association was found between any of the sedentary time-related variables and MFO (all P ≥ .05). However, several sedentary time-related variables were related to FATmax in young men and women (all P ≤ .04). A positive relationship was also detected between PA and MFO in young and middle-aged women (P ≤ .05), although this became non-significant after adjustment for cardiorespiratory fitness (P > .05). The present results suggest that, depending on the characteristics of the study cohort, sedentary time, and PA time may be related to MFO and FATmax during exercise. Future longitudinal and intervention studies are warranted to better understand the role of sedentary time and PA in metabolic flexibility during exercise.

Assessment of maximal fat oxidation during exercise: A systematic review.

Maximal fat oxidation during exercise (MFO) and the exercise intensity eliciting MFO (Fatmax ) are considered biological markers of metabolic health and performance. A wide range of studies have been performed to increase our knowledge about their regulation by exercise and/or nutritional intervention. However, numerous data collection and analysis approaches have been applied, which may have affected the MFO and Fatmax estimation. We aimed to systematically review the available studies describing and/or comparing different data collection and analysis approach factors that could affect MFO and Fatmax estimation in healthy individuals and patients. Two independent researchers performed the search. We included all original studies in which MFO and/or Fatmax were estimated by indirect calorimetry through an incremental graded exercise protocol published from 2002 to 2019. This systematic review provides key information about the factors that could affect MFO and Fatmax estimation: ergometer type, metabolic cart used, warm-up duration and intensity, stage duration and intensities imposed in the graded exercise protocol, time interval selected for data analysis, stoichiometric equation selected to estimate fat oxidation, data analysis approach, time of the day when the test was performed, fasting time/previous meal before the test, and testing days for MFO/Fatmax and maximal oxygen uptake assessment. We suggest that researchers measuring MFO and Fatmax should take into account these key methodological issues that can considerably affect the accuracy, validity, and reliability of the measurement. Likewise, when comparing different studies, it is important to check whether the above-mentioned key methodological issues are similar in such studies to avoid ambiguous and unacceptable comparisons.

Coupling Ultrafine Pt Nanocrystals over the Fe2P Surface as a Robust Catalyst for Alcohol Fuel Electro-Oxidation.

Ultrafine Pt nanocrystals with an average particle size of 2.2 ± 1 nm coupled over the petaloid Fe2P surface are proposed as a novel, efficient, and robust catalyst for alcohol fuel electro-oxidation. The strong coupling effect of metal-support imparts a strong electronic interaction between the Fe2P and Pt interface that can weaken the adsorption of poisoning CO species according to the d-band theory. Defects and increased surface area of the petaloid Fe2P are beneficial to the Pt nanoparticle anchoring and dispersion as well as the charge transfer and reactant transportation during the electrochemical reaction. These features make the Pt-Fe2P catalyst system exhibit excellent catalytic activity, antipoisoning ability, and catalytic stability for alcohol fuel of methanol and ethanol electro-oxidation compared with a controlled Pt/C catalyst. The high catalytic efficiency is proposed to come from the strong coupling effect of Pt and petaloid Fe2P interface that can maintain the mechanical and chemical stability of the catalyst system. This kind of phosphide-supported ultrafine Pt nanocrystals will be a promising catalyst in fuel cells.

Diurnal Variation of Maximal Fat-Oxidation Rate in Trained Male Athletes.

PURPOSE: To analyze the diurnal variation of maximal fat oxidation (MFO) and the intensity that elicits MFO (Fatmax) in trained male athletes. METHODS: A total of 12 endurance-trained male athletes age 24.7 (4.1) y participated in the study. The authors measured MFO, Fatmax, maximum oxygen uptake (VO2max), and VO2 percentage at ventilatory threshold 2 with a graded exercise protocol performed on 2 days separated by 1 wk. One test was performed in the morning and the other in the afternoon. The authors assessed the participants' chronotype using the HÖME questionnaire. RESULTS: MFO and Fatmax were greater in the afternoon than in the morning (Δ = 13%, P < .001 and Δ = 6%, P = .001, respectively), whereas there were similar VO2max and ventilatory threshold 2 in the morning, than in the afternoon test (Δ = 0.2%, P = .158 and Δ = 7%, P = .650, respectively). There was a strong positive association between VO2max and MFO in both morning and afternoon assessments (R2 = .783, P = .001 and R2 = .663, P < .001, respectively). Similarly, there was a positive association between VO2max and Fatmax in both morning and afternoon assessments (R2 = .406, P = .024 and R2 = .414, P = .026, respectively). CONCLUSION: MFO and Fatmax may partially explain some of the observed diurnal variation in the performance of endurance sports.

Metabolic flexibility to lipid availability during exercise is enhanced in individuals with high insulin sensitivity.

Metabolic flexibility to lipid (MetFlex-lip) is the capacity to adapt lipid oxidation to lipid availability. Hypothetically, impaired MetFlex-lip in skeletal muscle induces accumulation of lipid metabolites that interfere with insulin signaling. Our aim was to compare MetFlex-lip during exercise in subjects with low (Low_IS) vs. high (High_IS) insulin sensitivity. Twenty healthy men were designated as Low_IS or High_IS on the basis of the median of the homeostatic model assessment of insulin resistance index. Groups had similar age, body mass index, and maximum oxygen uptake (V̇o2max). Subjects cycled at 50% V̇o2max until expending 650 kcal. Adaptation in lipid oxidation was calculated as the drop in respiratory quotient (RQ) at the end of exercise vs. the maximum RQ (ΔRQ). Lipid availability was calculated as the increase in circulating nonesterified fatty acids (NEFA) at the end of exercise vs. the minimum NEFA (ΔNEFA). ΔRQ as a function of ΔNEFA was used to determine MetFlex-lip. On average, RQ and circulating NEFA changed similarly in both groups. However, ΔRQ correlated with ΔNEFA in High_IS ( r = -0.83, P < 0.01) but not in Low_IS ( r = -0.25, P = 0.48) subjects. Thus the slope of the ΔRQ vs. ΔNEFA relationship was steeper in High_IS vs. Low_IS subjects (-0.139 ± 0.03 vs. -0.025 ± 0.03 RQ·mmol-1·l-1, respectively; P < 0.05), with similar intercepts. We conclude that in subjects with High_IS lipid-to-carbohydrate oxidation ratio adapts to the increased circulating NEFA availability during exercise. Such MetFlex-lip appears impaired in subjects with Low_IS. Whether a cause-effect relationship exists between impaired MetFlex-lip and low insulin sensitivity remains to be determined.

Carbon Nanomaterials in Direct Liquid Fuel Cells.

Fuel cells have attracted more attentions due to many advantages they can provide, including high energy efficiency and low environmental burden. To form a stable, low cost and efficient catalyst, we presented here the state of the art of electrocatalyst fabrication approaches, involving carbon nanotubes and their multifunctional nanocomposites incorporated with noble metals, such as Pt, Pd, Au, their binary and ternary systems. Both fuel oxidation reactions and oxygen reduction reactions were emphasized with comprehensive examples and future prospects.

Ultrathin dendritic Pt3Cu triangular pyramid caps with enhanced electrocatalytic activity.

Here we report on the synthesis of novel dendritic Pt3Cu triangular pyramid caps via a solvothermal coreduction method. These caps had three-dimensional caved structures with ultrathin branches, as evidenced by high-resolution transmission electron microscopy (HRTEM) and HAADF-STEM characterization. Tuning the reduction kinetics of two metal precursors by an iodide ion was believed to be the key for the formation of an alloyed nanostructure. Electro-oxidation of methanol and formic acid showed dramatically improved electrocatalytic activities and poison-tolerance for these nanoalloys as compared to commercial Pt/C catalysts, which was attributed to their unique open porous structure with interconnected network, ultrahigh surface areas, as well as synergetic effect of the two metallic components.

Enhancing T3 and cAMP responsive gene participation in the thermogenic regulation of fuel oxidation pathways / Ampliando a participação dos genes responsivos a T3 e cAMP na regulação da termogênese gerada pelas vias de oxidação biológica

OBJECTIVE: We sought to identify glycolysis, glycogenolysis, lipolysis, Krebs cycle, respiratory chain, and oxidative phosphorylation enzymes simultaneously regulated by T3 and cAMP. MATERIALS AND METHODS: We performed in silico analysis of 56 promoters to search for cis-cAMP (CREB) and cis-thyroid (TRE) response elements, considering UCP1, SERCA2 and glyceraldehyde 3-phosphate dehydrogenase as reference. Only regulatory regions with prior in vitro validation were selected. RESULTS: 29/56 enzymes presented potential TREs in their regulatory sequence, and some scored over 0.80 (better predictive value 1): citrate synthase, phosphoglucose isomerase, succinate dehydrogenases A/C, UCP3, UCP2, UCP4, UCP5, phosphoglycerate mutase, glyceraldehyde 3-P dehydrogenase, glucokinase, malate dehydrogenase, acyl-CoA transferase (thiolase), cytochrome a3, and lactate dehydrogenase. Moreover, some enzymes have not yet been described in the literature as genomically regulated by T3. CONCLUSION: Our results point to other enzymes which may possibly be regulated by T3 and CREB, and speculate their joint roles in contributing to the optimal thermogenic acclimation.

OBJETIVO: Identificar enzimas das vias da glicólise, glicogenólise, lipólise, ciclo de Krebs, cadeia respiratória e fosforilação oxidativa possivelmente reguladas por T3 e cAMP. MATERIAIS E MÉTODOS: Analisamos 56 genes metabólicos in silico mediante a identificação dos elementos cis de regulação gênica responsivos ao T3 e cAMP (TREs, thyroid response elements e CREs, cAMP response elements), utilizando como referência o promotor da UCP1, SERCA2 e gliceraldeído 3-fosfato desidrogenase. Selecionamos somente os promotores com estudo funcional prévio in vitro. RESULTADOS: 29/56 enzimas apresentaram TREs em suas regiões regulatórias, parte com escore > 0,80 (melhor valor preditivo 1): citrato sintase, fosfoglucose isomerase, succinato desidrogenase A/C, UCP3, UCP2, UCP4, UCP5, fosfoglicerato mutase, gliceraldeído 3-P desidrogenase, glucoquinase, malato desidrogenase, acil-CoA transferase (tiolase), citocromo a3, e lactato desidrogenase; parte desconhecida como regulada por T3. CONCLUSÃO: Os resultados do presente estudo apontam para novos genes regulados por T3 e cAMP e, por conseguinte, sua contribuição na regulação da termogênese.