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La alta prevalencia de hipotiroidismo subclínico en Chile puede deberse a que el límite superior normal de la hormona estimulante del tiroides (TSH) sérica es bajo. Personas con TSH levemente mayor al límite superior pueden ser metabólicamente similares a personas sanas. Se compararon marcadores de acción tiroidea (gasto energético en reposo [GER] y lipoproteína de baja densidad [LDL]) en adultos con hipotiroidismo subclínico leve y con función tiroidea normal con o sin tratamiento con levotiroxina. Se midió GER, perfil lipídico y tiroideo en personas sanas con función tiroidea normal (TSH ≥0,4-<4,5 µUI/ml; n=91); con hipotiroidismo subclínico leve (TSH ≥4,5-≤6,5 µUI/ml; n=5); y con hipotiroidismo clínico tratado con levotiroxina y TSH normal (n=13). Se analizó la LDL en 838 personas sanas con función tiroidea normal y 89 con hipotiroidismo subclínico leve de la Encuesta Nacional de Salud 2016/17 (ENS). El GER, ajustado por peso, sexo y edad, fue similar entre grupos (p=0,71). La LDL fue similar entre personas con función tiroidea normal e hipotiroidismo subclínico leve (91±24 vs. 101±17 mg/dl; p=0,67), y menor en hipotiroidismo tratado (64±22 mg/dl; p<0,01). La LDL no se asoció con TSH pero si inversamente con T4L en mujeres (r=-0,33; p=0,02; n=53). En la ENS, ambos grupos tuvieron similar LDL (p=0,34), la que se asoció inversamente con T4L en mujeres (r=-0,12; p=0,01; n=569) pero no con TSH. Personas sanas con función tiroidea normal y con hipotiroidismo subclínico leve tienen similar GER y LDL. Esto apoya la idea de redefinir el límite superior normal de TSH.
The high prevalence of subclinical hypothyroidism in Chile may be due to the low normal upper limit of serum thyroid-stimulating hormone (TSH). People with TSH slightly higher than the upper limit may be metabolically similar to healthy people. Thyroid action markers (resting energy expenditure [REE] and low-density lipoprotein [LDL]) were compared in adults with mild subclinical hypothyroidism and with normal thyroid function with or without levothyroxine treatment. REE, lipid and thyroid profile were measured in healthy people with normal thyroid function (TSH ≥0,4-<4,5 µUI/ml (n=91); with mild subclinical hypothyroidism (TSH ≥4,5-≤6 µUI/ml; n=5); and with clinical hypothyroidism treated with levothyroxine and normal TSH (n=13). LDL was analyzed in 838 healthy people with normal thyroid function and 89 with mild subclinical hypothyroidism from the 2016/17 National Health Survey (NHS). REE, adjusted for weight, sex and age, was similar between the groups (p=0,71). LDL was similar between people with normal thyroid function and mild subclinical hypothyroidism (91±24 vs. 101±17 mg/dl; p=0,67), and lower in treated hypothyroidism (64±22 mg/dl; p<0,01). LDL was not associated with TSH but was inversely with FT4 in women (r=-0,33; p=0,02; n=53). In the NHS, both groups had similar serum LDL (p=0,34), which was inversely associated with FT4 in women (r=-0,12; p=0,01; n=569), but not with TSH. Healthy people with normal thyroid function and mild subclinical hypothyroidism have similar REE and LDL. These results support the idea of redefining the normal upper limit of TSH.
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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.
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Ciclo Menstrual , Paladar , Humanos , Feminino , Metabolismo Energético , Ingestão de Alimentos , AlimentosRESUMO
OBJECTIVE: To accurately estimate liver PDFF from chemical shift-encoded (CSE) MRI using a deep learning (DL)-based Multi-Decoder Water-Fat separation Network (MDWF-Net), that operates over complex-valued CSE-MR images with only 3 echoes. METHODS: The proposed MDWF-Net and a U-Net model were independently trained using the first 3 echoes of MRI data from 134 subjects, acquired with conventional 6-echoes abdomen protocol at 1.5 T. Resulting models were then evaluated using unseen CSE-MR images obtained from 14 subjects that were acquired with a 3-echoes CSE-MR pulse sequence with a shorter duration compared to the standard protocol. Resulting PDFF maps were qualitatively assessed by two radiologists, and quantitatively assessed at two corresponding liver ROIs, using Bland Altman and regression analysis for mean values, and ANOVA testing for standard deviation (STD) (significance level: .05). A 6-echo graph cut was considered ground truth. RESULTS: Assessment of radiologists demonstrated that, unlike U-Net, MDWF-Net had a similar quality to the ground truth, despite it considered half of the information. Regarding PDFF mean values at ROIs, MDWF-Net showed a better agreement with ground truth (regression slope = 0.94, R2 = 0.97) than U-Net (regression slope = 0.86, R2 = 0.93). Moreover, ANOVA post hoc analysis of STDs showed a statistical difference between graph cuts and U-Net (p < .05), unlike MDWF-Net (p = .53). CONCLUSION: MDWF-Net showed a liver PDFF accuracy comparable to the reference graph cut method, using only 3 echoes and thus allowing a reduction in the acquisition times. CLINICAL RELEVANCE STATEMENT: We have prospectively validated that the use of a multi-decoder convolutional neural network to estimate liver proton density fat fraction allows a significant reduction in MR scan time by reducing the number of echoes required by 50%. KEY POINTS: ⢠Novel water-fat separation neural network allows for liver PDFF estimation by using multi-echo MR images with a reduced number of echoes. ⢠Prospective single-center validation demonstrated that echo reduction leads to a significant shortening of the scan time, compared to standard 6-echo acquisition. ⢠Qualitative and quantitative performance of the proposed method showed no significant differences in PDFF estimation with respect to the reference technique.
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Fígado , Água , Humanos , Estudos Prospectivos , Fígado/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Abdome , Redes Neurais de Computação , Reprodutibilidade dos TestesRESUMO
Increasing moderate-vigorous physical activity (MVPA) through exercise requires reallocating time from other physical behaviour(s). We aimed to determine the reallocations induced by endurance exercise in physically active individuals. We also searched for behavioural compensatory responses, and explored the effect of exercise on daily energy expenditure. Fourteen participants (8 women; median age 37.8 [IQR 29.9-48.5] yr) exercised on Monday, Wednesday, and Friday mornings (cycling MVPA, 65â min/session; "exercise days"), and avoided exercising on Tuesday and Thursday ("rest days"). Time spent on sleep, sedentary behaviour, light-intensity physical activity, and MVPA was determined each day by accelerometers and logs. An energy expenditure index was computed considering minutes spent on each behaviour and fixed metabolic equivalents. We found that all participants had lower sleep and higher total (including exercise) MVPA on exercise days compared to rest days. Thus, on exercise vs. rest days, sleep was lower (490 [453-553] vs. 553 [497-599] min/day, respectively, P < 0.001), and total MVPA was higher (86 [80-101] vs. 23 [15-45] min/day, respectively; P < 0.001). No differences in other physical behaviours were detected. Notably, exercise not only induced reallocations (i.e. less time in other behaviours) but also behavioural compensatory responses in some participants (e.g. increased sedentary behaviour). This rearrangement of physical behaviours manifested in exercise-induced increases in energy expenditure from 96 to 232 MET × min/day. In conclusion, active individuals reallocated time from sleep to accommodate morning exercise. Yet exercise induced variable rearrangements of behaviours, with some individuals manifesting compensatory responses. Understanding individual rearrangements may help improve exercise interventions.
Adults are recommended to engage in moderate-vigorous physical activity (MVPA) to maintain health. But including exercise sessions within a day inevitably requires reallocating time from other physical behaviour(s): sleep, sedentary behaviour, or physical activity.We studied the time reallocations induced by 65â min/day of morning exercise (cycling MVPA) in physically active participants.Participants spent less time sleeping and higher time on total (including exercise) MVPA on days that included exercise compared to days without exercise. Thus, participants reallocated sleep time to accommodate morning exercise sessions.Some participants also spent higher time on sedentary behaviour during days that included exercise compared to days without exercise. This probably represents a behavioural compensatory response to exercise-induced fatigue.Together, time reallocations and behavioural compensatory responses led to a rearrangement of daily time spent on physical behaviours. This rearrangement was estimated to produce large interindividual variability in the increase in energy expenditure induced by exercise.
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Terapia por Exercício , Exercício Físico , Humanos , Feminino , Adulto , Exercício Físico/fisiologia , Sono , Comportamento Sedentário , Ciclismo , AcelerometriaRESUMO
The metabolic syndrome (MetS) is diagnosed upon the manifestation of ≥ 3 out of 5 specific components, regardless of their combination. The sequence through which these components accumulate may serve to identify underlying pathophysiological mechanisms and improve MetS treatment. We aimed to explore whether there is a more frequent sequence of accumulation of components in adults. The cross-sectional data of the National Health Survey of Chile 2016-2017 was analyzed. Subjects aged 18 to < 65 years, with body mass index ≥ 18.5 kg/m2, having all MetS components measured, and not under drug treatment were included (n = 1944, 60% women). MetS components were operationalized based on harmonized criteria: elevated waist circumference (≥ 91 cm for men, ≥ 83 cm for women), reduced high-density lipoprotein cholesterol (HDL-C; < 40 mg/dL for men, < 50 mg/dL for women), elevated triglycerides (≥ 150 mg/dL), elevated blood pressure (≥ 130 mmHg for systolic, or ≥ 85 mmHg for diastolic), and elevated glycemia (≥ 100 mg/dL). Subjects were grouped according to the number of components. Then, the prevalence of the observed combinations was determined. In subjects with one component, the most prevalent was waist circumference (56.7%). In subjects with two, the most prevalent combination was waist circumference and HDL-C (50.8%), while in subjects with three components was waist circumference, HDL-C, and triglycerides (54.0%). Finally, in subjects with four, the most prevalent combination was waist circumference, HDL-C, triglycerides, and blood pressure (40.8%). This pattern suggests that the most frequent accumulation sequence starts with abdominal obesity, followed by dyslipidemia, elevated blood pressure, and ultimately, dysglycemia. The factors that determine the sequence remain to be determined.
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Hipertensão , Síndrome Metabólica , Adulto , Glicemia/metabolismo , Pressão Sanguínea , Índice de Massa Corporal , HDL-Colesterol , Estudos Transversais , Feminino , Humanos , Hipertensão/epidemiologia , Masculino , Prevalência , Fatores de Risco , Triglicerídeos , Circunferência da CinturaRESUMO
Humans acquire energy from the environment for survival. A central question for nutritional sciences is how much energy is required to sustain cellular work while maintaining an adequate body mass. Because human energy balance is not exempt from thermodynamic principles, the energy requirement can be approached from the energy expenditure. Conceptual and technological advances have allowed understanding of the physiological determinants of energy expenditure. Body mass, sex, and age are the main factors determining energy expenditure. These factors constitute the basis for predictive equations for resting (REE) and total (TEE) energy expenditure in healthy adults. These equations yield predictions that differ up to ~400 kcal/d for REE and ~550 kcal/d for TEE. Identifying additional factors accounting for such variability and the most valid equations appears relevant. This review used novel approaches based on mathematical modeling of REE and analyses of the data from which REE predictive equations were generated. As for TEE, R2 and SE were considered because only a few predictive equations are available. From these analyses, Oxford's and Plucker's equations appear valid for predicting REE and TEE in adults, respectively.
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Metabolismo Energético , Condições Sociais , Adulto , Metabolismo Basal , Índice de Massa Corporal , Calorimetria Indireta , Metabolismo Energético/fisiologia , Humanos , Necessidades Nutricionais , DescansoRESUMO
Introduction: Unhealthy food choices increase the risk of obesity and its co-morbidities. Nutrition labels are a public health policy that aims to drive individuals toward healthier food choices. Chile has been an example of this policy, where mandatory nutrient warning labels (NWL) identify processed foods high in calories and critical nutrients. Eating contexts influence individual food choices, but whether eating contexts also influence how NWL alter the decision process and selection during food choice is unknown. Methods: In an online mouse-tracking study, participants prompted to health, typical, or unrestricted eating contexts were instructed to choose between pairs of foods in the presence or absence of NWL. Conflict during choices was analyzed using mouse paths and reaction times. Results: NWL increased conflict during unhealthy food choices and reduced conflict during healthy choices in all contexts. However, the probability that NWL reversed an unhealthy choice was 80% in a healthy, 37% in a typical, and 19% in an unrestricted context. A drift-diffusion model analysis showed the effects of NWL on choice were associated with an increased bias toward healthier foods in the healthy and typical but not in the unrestricted context. Discussion: These data suggest that the efficacy of NWL to drive healthy food choices increases in a healthy eating context, whereas NWL are less effective in typical or unrestricted eating contexts.
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Background: Low metabolic flexibility (MetF) may be an underlying factor for metabolic health impairment. Individuals with low MetF are thus expected to have worse metabolic health than subjects with high MetF. Therefore, we aimed to compare metabolic health in individuals with contrasting MetF to an oral glucose tolerance test (OGTT). Methods: In individuals with excess body weight, we measured MetF as the change in respiratory quotient (RQ) from fasting to 1 h after ingestion of a 75-g glucose load (i.e., OGTT). Individuals were then grouped into low and high MetF (Low-MetF n = 12; High-MetF n = 13). The groups had similar body mass index, body fat, sex, age, and maximum oxygen uptake. Metabolic health markers (clinical markers, insulin sensitivity/resistance, abdominal fat, and intrahepatic fat) were compared between groups. Results: Fasting glucose, triglycerides (TG), and high-density lipoprotein (HDL) were similar between groups. So were insulin sensitivity/resistance, visceral, and intrahepatic fat. Nevertheless, High-MetF individuals had higher diastolic blood pressure, a larger drop in TG concentration during the OGTT, and a borderline significant (P = 0.05) higher Subcutaneous Adipose Tissue (SAT). Further, compared to Low-MetF, High-MetF individuals had an about 2-fold steeper slope for the relationship between SAT and fat mass index. Conclusion: Individuals with contrasting MetF to an OGTT had similar metabolic health. Yet High-MetF appears related to enhanced circulating TG clearance and enlarged subcutaneous fat.
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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].
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The constrained total energy expenditure (TEE) model posits that progressive increases in physical activity (PA) lead to increases in TEE; but after certain PA threshold, TEE plateaus. Then, a compensatory reduction in the expenditure of non-essential activities constrains the TEE. We hypothesized that high PA levels as locomotion associate with a compensatory attenuation in arm movements. We included 209 adults (64% females, mean [SD] age 32.1 [15.0] years) and 105 children (40% females, age 10.0 [1.1] years). Subjects wore, simultaneously, one accelerometer in the non-dominant wrist and another in the hip for ≥ 4 days. We analyzed the association between wrist-measured (arm movements plus locomotion) and hip-measured PA (locomotion). We also analyzed how the capacity to dissociate arm movements from locomotion influences total PA. In adults, the association between wrist-measured and hip-measured PA was better described by a quadratic than a linear model (Quadratic-R2 = 0.54 vs. Linear-R2 = 0.52; P = 0.003). Above the 80th percentile of hip-measured PA, wrist-measured PA plateaued. In children, there was no evidence that a quadratic model fitted the association between wrist-measured and hip-measured PA better than a linear model (R2 = 0.58 in both models, P = 0.25). In adults and children, those with the highest capacity to dissociate arm movements from locomotion-i.e. higher arm movements for a given locomotion-reached the highest total PA. We conclude that, in adults, elevated locomotion associates with a compensatory reduction in arm movements (probably non-essential fidgeting) that partially explains the constrained TEE model. Subjects with the lowest arm compensation reach the highest total PA.
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Sistema Endócrino/fisiologia , Metabolismo Energético/fisiologia , Exercício Físico/fisiologia , Obesidade/metabolismo , Acelerometria , Adolescente , Adulto , Peso Corporal , Criança , Feminino , Quadril/fisiologia , Homeostase/genética , Humanos , Masculino , Doenças Metabólicas/epidemiologia , Doenças Metabólicas/metabolismo , Doenças Metabólicas/patologia , Obesidade/epidemiologia , Obesidade/patologia , Punho/fisiologia , Adulto JovemRESUMO
Glucose, fatty acids, and amino acids among others are oxidized to generate adenosine triphosphate (ATP). These fuels are supplied from the environment (through food intake) and internal depots (through lipolysis, glycogenolysis, and proteolysis) at different rates throughout the day. Complex adaptive systems permit to accommodate fuel oxidation according to fuel availability. This capacity of a cell, tissue, or organism to adapt fuel oxidation to fuel availability is defined as metabolic flexibility (MetF). There are conditions, such as insulin resistance, diabetes, and obesity, in which MetF seems to be impaired. The observation that those conditions are accompanied by mitochondrial dysfunction has set the basis to propose a link between mitochondrial dysfunction, metabolic inflexibility, and metabolic health. We here highlight the evidence about the notion that MetF influences metabolic health.
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Metabolismo Energético , Aminoácidos/metabolismo , Ácidos Graxos/metabolismo , Glucose/metabolismo , Glicogenólise , Humanos , Resistência à Insulina , Lipólise , Mitocôndrias/patologia , Obesidade , Oxirredução , ProteóliseRESUMO
Methylation in CpG sites of the PPARGC1A gene (encoding PGC1-α) has been associated with adiposity, insulin secretion/sensitivity indexes and type 2 diabetes. We assessed the association between the methylation profile of the PPARGC1A gene promoter gene in leukocytes with insulin secretion/sensitivity indexes in normoglycemic women. A standard oral glucose tolerance test (OGTT) and an abbreviated version of the intravenous glucose tolerance test (IVGTT) were carried out in n = 57 Chilean nondiabetic women with measurements of plasma glucose, insulin, and C-peptide. Bisulfite-treated DNA from leukocytes was evaluated for methylation levels in six CpG sites of the proximal promoter of the PPARGC1A gene by pyrosequencing (positions -816, -783, -652, -617, -521 and -515). A strong correlation between the DNA methylation percentage of different CpG sites of the PPARGC1A promoter in leukocytes was found, suggesting an integrated epigenetic control of this region. We found a positive association between the methylation levels of the CpG site -783 with the insulin sensitivity Matsuda composite index (rho = 0.31; p = 0.02) derived from the OGTT. The CpG hypomethylation in the promoter position -783 of the PPARGC1A gene in leukocytes may represent a biomarker of reduced insulin sensitivity after the ingestion of glucose.
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Glicemia , Metilação de DNA/genética , Resistência à Insulina/genética , Secreção de Insulina/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Regiões Promotoras Genéticas/genética , Adulto , Biomarcadores/sangue , Chile , Feminino , HumanosRESUMO
BACKGROUND: Lifestyle habits associate with metabolic health in overall populations. Whether such association is similar among subjects with a different nutritional status has been less studied. We aimed to (i) determine the prevalence of metabolic phenotypes in Chile, and (ii) determine the association between lifestyle habits and metabolic health according to the nutritional status. METHODS: The National Health Survey of Chile 2016-2017 was analyzed. A metabolically unhealthy phenotype was defined as manifesting ≥3 of the following risk factors: elevated blood pressure, elevated triglycerides, elevated glucose, elevated waist circumference, or reduced high-density lipoprotein cholesterol. Individuals manifesting <2 risk factors were considered as healthy. The nutritional status was defined as normal weight (18.5 to <25 kg/m2), overweight (25 to <30 kg/m2) or obesity (≥30 kg/m2). Questionnaires were used to estimate smoking habits, alcohol intake, sedentary behavior, moderate-vigorous physical activity, fruits/vegetables consumption, and fish/seafood consumption. The association (odds ratio [95%CI]) between lifestyle habits and metabolic health was determined within each nutritional status, adjusting for age, sex, BMI (in kg/m2), and education. RESULTS: The prevalence of a metabolically unhealthy phenotype was 36% in the overall sample. Such a prevalence was 7%, 33% and 58% among subjects with normal weight, overweight and obesity, respectively. In subjects with normal weight, the highest quartile of fruits/vegetables consumption was associated with reduced odds of having a metabolically unhealthy phenotype (0.09 [0.01-0.48]). In subjects with obesity, the highest quartile of moderate-vigorous physical activity was associated with reduced odds of having a metabolically unhealthy phenotype (0.29 [0.09-0.91]). CONCLUSION: One third of the Chilean population manifests an unhealthy phenotype. We identified associations between lifestyle habits and metabolic health that are specific to the nutritional status. Thus, emphasizing fruits/vegetables consumption in subjects with normal weight, and physical activity in subjects with obesity, may maximize the benefits of public health interventions.
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Hábitos , Estilo de Vida , Síndrome Metabólica/epidemiologia , Estado Nutricional/fisiologia , Adolescente , Adulto , Idoso , Glicemia/análise , Chile/epidemiologia , HDL-Colesterol/sangue , Estudos Transversais , Escolaridade , Feminino , Inquéritos Epidemiológicos/estatística & dados numéricos , Humanos , Hipertensão/sangue , Hipertensão/epidemiologia , Hipertensão/metabolismo , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/metabolismo , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/diagnóstico , Obesidade/epidemiologia , Obesidade/metabolismo , Sobrepeso/sangue , Sobrepeso/epidemiologia , Sobrepeso/metabolismo , Prevalência , Fatores de Risco , Circunferência da Cintura/fisiologia , Adulto JovemRESUMO
OBJECTIVE: This study aimed to determine the relationship between metabolic flexibility (MetFlex) measured during a euglycemic-hyperinsulinemic clamp and a prolonged fast. This study also analyzed the association between MetFlex and metabolic health. METHODS: Eighteen healthy men (mean [SD]: 22 [2] years old; BMI: 22 [1] kg/m2 ) performed two sessions: (1) euglycemic-hyperinsulinemic clamp (2 mIU/kg of insulin per minute) and (2) ~20-hour fast. Clamp MetFlex corresponded to the change in (Δ) respiratory quotient (RQ) (ΔRQ = postchallenge RQ - prechallenge RQ) adjusted for M value and prechallenge RQ. Prolonged fast MetFlex corresponded to the ΔRQ adjusted for the Δß-hydroxybutyrate and prechallenge RQ. RESULTS: MetFlex during the clamp related directly with MetFlex during prolonged fast (r = 0.59, P = 0.014). Using the median of MetFlex for each challenge, this study split participants into high or low MetFlex. Participants with high or low MetFlex to both challenges were identified. Participants with high MetFlex had 3% lower serum low-density lipoprotein cholesterol than participants with low MetFlex (P = 0.021). CONCLUSIONS: Measuring MetFlex during a clamp or a prolonged fast produces similar results, despite challenging the oxidation of different substrates. An impaired MetFlex in response to these challenges may be an early event in the development of abnormal lipid metabolism.
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Jejum/fisiologia , Técnica Clamp de Glucose/métodos , Resistência à Insulina/fisiologia , Insulina/sangue , Adulto , Humanos , Masculino , Adulto JovemRESUMO
The present "obesogenic' environment has favored excessive energy intake resulting in the current obesity epidemic and its associated diseases. The epidemic has incentivized scientists to develop novel behavioral and pharmacological strategies that enhance energy expenditure to compensate for excessive energy intake. Although physical activity is effective to increase total energy expenditure, it is insufficient to induce negative energy balance and weight loss. With the discovery of brown adipose tissue (BAT) in adult humans, BAT activation soon emerged as a potential strategy for elevating energy expenditure. BAT is the only tissue that expresses uncoupling protein 1, conferring on this tissue high thermogenic capacity due to a low efficiency for mitochondrial ATP generation. Potential manipulation of BAT mass and activity has fueled the interest in altering whole-body energy balance through increased energy expenditure. Remarkable advances have been made in quantifying the amount and activity of BAT in humans. Many studies have concluded that the amount of active BAT appears insufficient to induce meaningful increases in energy expenditure. Thus, the majority of studies report that BAT activation does not influence body weight and metabolic control in humans. Strategies to increase BAT mass and/or to potentiate BAT activity seem necessary.
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Tecido Adiposo Marrom/fisiologia , Metabolismo Energético , Tecido Adiposo Marrom/anatomia & histologia , Animais , Peso Corporal , Humanos , Modelos Biológicos , Tamanho do Órgão , Termogênese/fisiologiaRESUMO
Sucralose is an artificial non-nutritive sweetener used in foods aimed to reduce sugar and energy intake. While thought to be inert, the impact of sucralose on metabolic control has shown to be the opposite. The gut microbiome has emerged as a factor shaping metabolic responses after sweetener consumption. We examined the short-term effect of sucralose consumption on glucose homeostasis and gut microbiome of healthy male volunteers. We performed a randomised, double-blind study in thirty-four subjects divided into two groups, one that was administered sucralose capsules (780 mg/d for 7 d; n 17) and a control group receiving placebo (n 17). Before and after the intervention, glycaemic and insulinaemic responses were assessed with a standard oral glucose load (75 g). Insulin resistance was determined using homeostasis model assessment of insulin resistance and Matsuda indexes. The gut microbiome was evaluated before and after the intervention by 16S rRNA sequencing. During the study, body weight remained constant in both groups. Glycaemic control and insulin resistance were not affected during the 7-d period. At the phylum level, gut microbiome was not modified in any group. We classified subjects according to their change in insulinaemia after the intervention, to compare the microbiome of responders and non-responders. Independent of consuming sucralose or placebo, individuals with a higher insulinaemic response after the intervention had lower Bacteroidetes and higher Firmicutes abundances. In conclusion, consumption of high doses of sucralose for 7 d does not alter glycaemic control, insulin resistance, or gut microbiome in healthy individuals. However, it highlights the need to address individual responses to sucralose.
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Ingestão de Energia/fisiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Sacarose/análogos & derivados , Edulcorantes/farmacologia , Adolescente , Adulto , Glicemia/efeitos dos fármacos , Método Duplo-Cego , Voluntários Saudáveis , Humanos , Resistência à Insulina/fisiologia , Masculino , RNA Ribossômico 16S/análise , Sacarose/farmacologia , Adulto JovemRESUMO
Most peripheral serotonin (5-hydroxytryptamine (5HT)) is synthetized in the gut with platelets being its main circulating reservoir. 5HT is acting as a hormone in key organs to regulate glucose and lipid metabolism. However, the relation between platelet 5HT levels and traits related to glucose homeostasis and lipid metabolism in humans remains poorly explored. The objectives of this study were (a) to assess the association between platelet 5HT levels and plasma concentration of nonesterified fatty acids (NEFAs) and some adipokines including leptin and its soluble leptin receptor (sOb-R), (b) to assess the association between platelet 5HT levels and anthropometric traits and indexes of insulin secretion/sensitivity derived from oral glucose tolerance test (OGTT), and (c) to evaluate changes in platelet 5HT levels in response to OGTT. In a cross-sectional study, 59 normoglycemic women underwent a standard 2-hour OGTT. Plasma leptin, sOb-R, total and high molecular weight adiponectin, TNFα, and MCP1 were determined by immunoassays. Platelet 5HT levels and NEFAs were measured before and after OGTT. The free leptin index was calculated from leptin and sOb-R measurements. Insulin sensitivity indexes derived from OGTT (HOMA-S and Matsuda ISICOMP) and plasma NEFAs (Adipose-IR, Revised QUICKI) were also calculated. Our data show that among metabolic traits, platelet 5HT levels were associated with plasma sOb-R (r = 0.39, p = 0.003, corrected p = 0.018). Platelet 5HT levels were reduced in response to OGTT (779 ± 237 vs.731 ± 217 ng/109 platelets, p = 0.005). In conclusion, platelet 5HT levels are positively associated with plasma sOb-R concentrations and reduced in response to glucose intake possibly indicating a role of peripheral 5HT in leptin-mediated appetite regulation.
Assuntos
Adipocinas/sangue , Plaquetas/química , Receptores para Leptina/sangue , Serotonina/sangue , Adiponectina/sangue , Adulto , Antropometria , Glicemia/análise , Índice de Massa Corporal , Quimiocina CCL2/sangue , Chile , Estudos Transversais , Ácidos Graxos não Esterificados/metabolismo , Feminino , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Resistência à Insulina , Leptina/sangue , Metabolismo dos Lipídeos , Lipídeos/sangue , Receptores para Leptina/genética , Fator de Necrose Tumoral alfa/sangue , Adulto JovemRESUMO
High plasma lactate levels have been associated with reduced mitochondrial respiratory capacity and increased type 2 diabetes risk, while mitochondrial DNA (mtDNA) copy number has been proposed as a biomarker of mitochondrial function linked to glucose homeostasis. The aim of this study was to evaluate the association between circulating lactate levels and leukocyte mtDNA copy numbers with insulin secretion/sensitivity indexes in 65 Chilean non-diabetic women. mtDNA copy numbers were measured in leukocytes using qPCR and digital-droplet PCR. A 75-g Oral Glucose Tolerance Test (OGTT) was performed to calculate systemic and tissue-specific insulin sensitivity indexes, as well as insulin secretion surrogates based on plasma c-peptide. An intravenous glucose tolerance test (IVGTT; 0.3 g/kg) was also carried out. Disposition indexes were calculated as the product of insulin secretion × sensitivity. Plasma levels of leptin, adiponectin, TNF-α, MCP-1, and non-esterified fatty acids were also determined. Fasting plasma lactate shows a significant association with a wide range of insulin sensitivity/resistance indexes based on fasting plasma samples (HOMA-S, adipose IR index, Revised-QUICKI, leptin-adiponectin ratio, TyG index, McAuley index and TG-to-HDL-C ratio), as well as OGTT-based measures such as the Matsuda index, the hepatic insulin resistance index, and the disposition index. Fasting plasma lactate was also positively associated with the circulating adipokines TNF-α and MCP-1. We also detected a direct association between fasting plasma lactate with leukocyte mtDNA copy numbers. The above results support the use of fasting plasma lactate, and possibly leukocyte mtDNA copy numbers, as biomarkers of reduced oxidative mitochondrial capacity, decreased hepatic insulin sensitivity, and future diabetes risk.