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Ítem Effects of ketone bodies on energy expenditure, substrate utilization, and energy intake in humans(American Society for Biochemistry and Molecular Biology, 2023-09-11) Fernández-Verdejo, RodrigoRecientemente se ha prestado atención al potencial de los enfoques cetogénicos para regular el equilibrio energético, ya que las cetonas pueden influir tanto en el gasto como en la ingesta de energía. En esta revisión narrativa, resumimos la evidencia más relevante sobre el papel de la cetosis en el gasto de energía, la utilización de sustratos y la ingesta de energía en humanos. Consideramos diferentes estrategias para inducir la cetosis, como el ayuno, la manipulación dietética y las fuentes exógenas de cetonas. En general, la cetosis no tiene una influencia importante en el gasto energético, pero promueve un cambio en la utilización del sustrato hacia la oxidación de los cuerpos cetónicos. Las estrategias para inducir la cetosis mediante la reducción de la disponibilidad de carbohidratos en la dieta (p. ej., dietas cetogénicas) no influyen de forma independiente en la ingesta de energía, por lo que son igualmente efectivas para perder peso que las dietas con mayor contenido de carbohidratos. Por el contrario, la ingesta de triglicéridos de cadena media y ésteres de cetonas induce cetosis y parece aumentar el gasto energético y reducir la ingesta energética en el contexto de una alta disponibilidad de carbohidratos. Estas últimas estrategias conducen a una pérdida de peso ligeramente mayor. Desafortunadamente, distinguir los efectos de las diversas estrategias cetogénicasper se de los efectos de otras respuestas fisiológicas no es posible con los datos humanos disponibles. Se necesitan estudios hospitalarios altamente controlados que utilicen estrategias específicas para aislar los efectos independientes de las cetonas para abordar adecuadamente esta brecha de conocimiento.Ítem Energy expenditure in humans: principles, methods, and changes throughout the life course(Annual Reviews Inc., 2024-05-17) Fernández-Verdejo, RodrigoHumans require energy to sustain their daily activities throughout their lives. This narrative review aims to (a) summarize principles and methods for studying human energy expenditure, (b) discuss the main determinants of energy expenditure, and (c) discuss the changes in energy expenditure throughout the human life course. Total daily energy expenditure is mainly composed of resting energy expenditure, physical activity energy expenditure, and the thermic effect of food. Total daily energy expenditure and its components are estimated using variations of the indirect calorimetry method. The relative contributions of organs and tissues determine the energy expenditure under different physiological conditions. Evidence shows that energy expenditure varies along the human life course, at least in part due to changes in body composition, the mass and specific metabolic rate of organs and tissues, and levels of physical activity. This information is crucial to estimate human energy requirements for maintaining health throughout the life course.Ítem Exploring the sequential accumulation of metabolic syndrome components in adults(Springer Nature, 2022) Fernández-Verdejo, RodrigoThe 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.Ítem Gasto energético en reposo y concentración sérica de lipoproteínas de baja densidad en adultos con hipotiroidismo subclínico leve(Sociedad Chilena de Nutrición, Bromatología y Toxicología, 2024-04-01) Fernández-Verdejo, RodrigoLa 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.Ítem Leveraging shared variation among traits for the discovery of genetic variants in complex phenotypes such as obesity(Wiley; The Obesity Society, 2025-06-01) Fernández-Verdejo, RodrigoIdentifying genetic variants associated with obesity is critical forunderstanding the role of genetics and its interaction with the envi-ronment in the regulation of body weight. Hundreds of genetic vari-ants have been identified so far, mostly associated with body massindex (BMI). Nevertheless, given the complex pathogenesis andthe evolving definition and diagnosis of obesity, exploring traitsbeyond BMI becomes crucial to advancing the field. Obesityresults from a prolonged positive energy balance, during which energyintake exceeds energy expenditure. Therefore, identifying geneticvariants associated with energy balance-related traits should provideadditional insight into the genetic basis of obesity.Ítem Metabolic elasticity — a new trait associated with health?(Nature Publishing Group, 2023-10-13) Fernández-Verdejo, RodrigoA recent study by Zhou and colleagues proposed that low metabolic elasticity and gene elasticity are involved in the metabolic alterations observed in ageing and obesity. Here, we discuss some of their findings to provide a viewpoint on these potential new traits associated with metabolic health.Ítem Predictive equations for energy expenditure in adult humans: From resting to free-living conditions(Wiley; The Obesity Society, 2022-07-19) Fernández-Verdejo, RodrigoHumans 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.Ítem Prevalence of non-alcoholic fatty liver disease and its association with lifestyle habits in adults in Chile: a cross-sectional study from the National Health Survey 2016-2017(Cambridge University Press, 2023-01) Fernández-Verdejo, RodrigoNon-alcoholic fatty liver disease (NAFLD) represents an excessive fat accumulation within the liver, usually associated with excess body weight. A liver biopsy is the gold standard for diagnosis, but it is inapplicable in population-based studies. In large populations, non-invasive methods could be used, which may also serve to identify potential protective factors. We aimed to: [a] estimate NAFLD prevalence in the adult population in Chile by using non-invasive methods; and [b] determine the association between the presence of NAFLD and lifestyle habits. The National Health Survey of Chile 2016-2017 was analysed. We included individuals aged 21-75 years, without infectious diseases nor risky alcohol consumption. NAFLD was detected by either Fatty Liver Index (FLI; considers circulating triglycerides, circulating gamma-glutamyl-transferase, body mass index, and waist circumference), Lipid Accumulation Product (LAP; considers sex, circulating triglycerides, and waist circumference), or their combination. Lifestyle habits were determined by questionnaires. We included 2,774 participants, representative of 10,599,094 [9,831,644-11,366,544] adults in Chile. NAFLD prevalence [95%CI] was 39.4% [36.2-42.8] by FLI, 27.2% [24.2-30.4] by LAP, and 23.5% [20.7-26.5] by their combination. The prevalence progressively increased with increasing body mass index. Less smoking, and more moderate-vigorous physical activity and whole-grain consumption were associated with lower odds of having NAFLD, independently of body mass index. At least one out of four adults in Chile is afflicted with NAFLD. Health promotion strategies focused on controlling excess body weight and promoting specific lifestyle habits are urgently required.Ítem Resting energy metabolism and sweet taste preference during the menstrual cycle in healthy women(Newcastle University Population Health Sciences Inst, 2023-08-29) Fernández-Verdejo, RodrigoDifferences 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, drm = 0·33), while RQ showed borderline significant higher values (0·84 (SD 0·05) v.0·81 (SD 0·05), respectively; P = 0·07; drm = 0·62). Also, in the FP v. LP, sweet taste preference was lower (12 (SD 8) v. 16 (SD 9) %; P = 0·04;drm = 0·47) concomitant with higher serum FGF21 concentration (294 (SD 164) v. 197 (SD 104) pg/ml; P < 0·01; drm = 0·66). The menstrual cycle is associated with changes in energy expenditure, sweet taste preference and oxidative fuel partitioning.Ítem Similar metabolic health in overweight/obese individuals with contrasting metabolic flexibility to an oral glucose tolerance test(Frontiers Media S.A., 2021-11-16) Fernández-Verdejo, RodrigoBackground: 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; HighMetF 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.