Artículos de Revistas

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Metabolic elasticity — a new trait associated with health?
(Nature Publishing Group, 2023-10-13) Fernández-Verdejo, Rodrigo; Galgani, Jose E.
A 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.
Time reallocation of physical behaviours induced by endurance exercise in physically active individuals
(Taylor & Francis, 2023-04-16) Hayes-Ortiz, Thomas; Suárez-Reyes, Mónica; Galgani, José E.; Zbinden-Fonseca, Hermann; Fernández-Verdejo, Rodrigo
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, 65 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.
Upper-Limb disability and the severity of lymphedema reduce the quality of life of patients with breast cancer-related lymphedema
(MDPI, 2023) Ramírez-Parada, Karol; Gonzalez-Santos, Angela; Riady-Aleuy, Layla; Pinto P., Mauricio; Ibáñez, Carolina; Merino, Tomas; Acevedo, Francisco; Walbaum, Benjamín; Fernández-Verdejo, Rodrigo
Breast cancer-related lymphedema (BCRL) is characterized by arm swelling, pain, and discomfort, reducing the quality of life (QoL) of affected individuals. BRCL is caused via the blockage or disruption of the lymphatic vessels following cancer treatments, leading to an accumulation of fluid in the affected arm. While current BCRL rehabilitation treatments seek to reduce arm swelling, our study aimed to examine the impact of both the magnitude of lymphedema (ΔVolume) and arm disability on three dimensions of QoL: social, physical, and psychological. Using the Disabilities of the Arm, Shoulder, and Hand questionnaire (DASH) and the Upper Limb Lymphedema 27 questionnaire (ULL) in a group of 30 patients, we found that the magnitude of lymphedema (ΔVolume) was associated with the social dimension of QoL (r = 0.37, p = 0.041), but not with other dimensions. On the other hand, arm disability was associated with all evaluated dimensions of QoL (social, physical, and psychological: p < 0.001, p = 0.019, and p = 0.050 (borderline), respectively). These findings suggest that BCRL rehabilitation strategies should not only aim to reduce the magnitude of lymphedema but should also seek to improve or preserve arm functionality to enhance the QoL of BCRL patients.
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, Rodrigo; Malo-Vintimilla, Lorena; Aguirre, Carolina; Vergara, Angie; Galgani, Jose E.
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, 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.
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, Rodrigo; Mey, Jacob T.; Ravussin, Eric
Recientemente 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.
Elevated Risk of Overweight/Obesity-Related Markers and Low Muscular Fitness in Children Attending Public Schools in Chile
(International Journal of Environmental Research and Public Health, 2022) Suárez-Reyes, Mónica; Fernández-Verdejo, Rodrigo
In Chile, children of low socioeconomic status usually attend public schools and have few opportunities to engage in healthy behaviors. This may increase their risk of overweight/obesity and low muscular fitness. Therefore, we aimed to determine the association between the school type attended with overweight/obesity-related markers and the muscular fitness of children in Chile. We included 1410 children (6–13 years old) attending public, subsidized, or private schools. Overweight/obesity-related markers included BMI Z-scores, waist circumference, and body fat percentage. Muscular fitness assessment included handgrip strength and standing long jump. The odds ratios [95% CI] of overweight/obesity, elevated waist circumference, elevated body fat, low handgrip strength, and low standing long jump were compared between school types. Compared with boys attending public schools, those attending subsidized or private schools had lower odds ratios of low handgrip strength (0.63 [0.42–0.94] and 0.44 [0.25–0.78], respectively). Girls attending subsidized schools, compared with those in public schools, had lower odds of overweight/obesity (0.63 [0.44–0.90]) and of having low handgrip strength (0.51 [0.34–0.78]). Compared with girls in public schools, those attending private schools had lower odds (vs. public schools) of overweight/obesity (0.45 [0.28–0.74]), of having elevated body fat (0.53 [0.29–0.96]), and of having low standing long jump (0.41 [0.21–0.77]). The elevated risk of overweight/obesity-related markers and lower muscular fitness in children, particularly girls, attending public schools increase their current and future disease risk. This suggests that childhood socioeconomic status plays a central role in determining disease risk. Health-promoting interventions specifically focused on children from disadvantaged contexts are required.
Work/household, transport, and leisure domains account for the sex gap in physical activity in Chile
(Frontiers in Public Health, 2022) Suárez-Reyes, Mónica; Fernández-Verdejo, Rodrigo
Exploring the sequential accumulation of metabolic syndrome components in adults
(Scientific Reports, 2022) Fernández-Verdejo, Rodrigo
¿Los niveles de Testosterona y Cortisol influyen en el rendimiento en el rugby? Una mirada al rugby sevens.
(2022-04-30) Zúñiga-Vergara., Pedro; Castro-Sepulveda, Mauricio
Resumen: Introducción: El Rugby 7 (R7) es una rama del Rugby Unión (RU) y se caracteriza principalmente por ser un deporte de oposición con períodos de juego intensos y de corta duración, por lo tanto, los componentes psicológicos y fisiológicos juegan un rol en el rendimiento. En el R7, los deportistas compiten varias veces durante un mismo día, permitiendo la acumulación de fatiga. Esta acumulación de fatiga se puede explicar principalmente por la intensidad del juego y el número de colisiones a alta intensidad provocando perturbaciones a nivel muscular, endocrino y del sistema inmune. Sin embargo, a la fecha no existen trabajos que integren las respuestas fisiológicas como, por ejemplo, las respuestas hormonales de los jugadores a dichas demandas. Objetivo: Realizar una revisión de la literatura científica en relación al efecto de las hormonas T, C y el Ratio T/C en el rendimiento deportivo en el R7. Metodología: Revisión narrativa de la literatuta, se realizó una búsqueda durante los meses de abril a noviembre del 2021 en 4 bases de datos (Pubmed/Medline, Google Scholar, Scopus (Elsevier) y Scielo). Después de analizar 335 textos se consideró su utilidad y relevacia para la inclusión a esta revisión. 11 Estudios cumplierón con los criterios de inclusión. Resultados: Los trabajos incluidos asocián la relación hormonal con el rendimiento deportivo en el RU y R7. Se destaca la relación grande (r=0,80) de la T con el rendimiento deportivo en el RU. Conclusión: Según los estudios analizados se puede observar
Severe COVID-19 correlates with lower mitochondrial cristae density in PBMCs and greater sitting time in humans
(2022-05-27) Castro-Sepulveda, Mauricio; Tapia, German; Tuñón-Suárez, Mauro; Marambio, Hugo; Valero-Breton, Mayalen; Fernández-Verdejo, Rodrigo; Zbinden-Foncea, Hermann
An interaction between mitochondrial dynamics, physical activity levels, andCOVID-19 severity has been previously hypothesized. However, this has notbeen tested. We aimed to compare mitochondrial morphology and cristae den-sity of PBMCs between subjects with non- severe COVID- 19, subjects with se-vere COVID- 19, and healthy controls. Additionally, we compared the level ofmoderate-vigorous physical activity (MVPA) and sitting time between groups.Blood samples were taken to obtain PBMCs. Mitochondrial dynamics were as-sessed by electron microscopy images and western blot of protein that regulatemitochondrial dynamics. The International Physical Activity Questionnaire(IPAQ; short version) was used to estimate the level of MVPA and the sitting timeThe patients who develop severe COVID-19 (COVID-19++) not present altera-tions of mitochondrial size neither mitochondrial density in comparison to non-severe patients COVID- 19 (COVID- 19) and control subjects (CTRL). However,compared to CTRL, COVID- 19 and COVID-19++ groups have lower mitochon-drial cristae length, a higher proportion of abnormal mitochondrial cristae. TheCOVID-19++ group has lower number (trend) and length of mitochondrial cris-tae in comparison to COVID- 19 group. COVID- 19, but not COVID- 19++ grouphad lower Opa 1, Mfn 2 and SDHB (Complex II) proteins than CTRL group.Besides, COVID-19++ group has a higher time sitting. Our results show that lowmitochondrial cristae density, potentially due to physical inactivity, is associatedwith COVID-19 severity.
Predictive equations for energy expenditure in adult humans: From resting to free-living conditions
(Wiley, 2022) Fernández-Verdejo, Rodrigo; Galgani, José E
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.
Effect of supervised resistance training on arm volume, quality of life and physical perfomance among women at high risk for breast cancer-related Lymphedema: A study protocol for a randomized controlled Trial (STRONG-B)
(Frontiers Media, 2022-03) Ramírez-Parada, Karol; Lopez-Garzon, Maria; Sanchez-Rojel, Cesar; Petric-Guajardo, Militza; Alfaro-Barra, Margarita; Fernández-Verdejo, Rodrigo; Reyes-Ponce, Alvaro; Merino-Pereira, Gina; Cantarero-Villanueva, Irene
Objectives: To determine the preventive effects of supervised resistance training on arms volume, quality of life, physical performance, and handgrip strength in Chilean women at high risk for breast cancer-related lymphedema (BCRL) undergoing chemotherapy. Design: Randomized control trial. Participants: One hundred and six women at high risk for breast cancer-related lymphedema aged 18 to 70 years. Interventions: Participants will be randomized into two groups: [a] intervention, who will receive 12 weeks of supervised resistance training (STRONG-B) during adjuvant chemotherapy; and [b] control, who will receive education to promote lymphatic and venous return, maintain range of motion, and promote physical activity. Main Outcome Measures: The primary outcome will be arms volume measured with an optoelectric device (perometer NT1000). Secondary outcomes will be quality of life, handgrip strength, and physical performance. Primary and secondary outcomes will be measured at baseline, just after the intervention, and 3 and 6 months after. Statistical analysis will be performed following intention-to-treat and per-protocol approaches. The treatment effect will be calculated using linear mixed models. Discussion: The STRONG-B will be a tailored supervised resistance training that attempts to prevent or mitigate BCRL in a population that, due to both intrinsic and extrinsic factors, will commonly suffer from BCRL. Clinical Trial Registration: [https://clinicaltrials.gov/ct2/show/NCT04821609], identifier NCT04821609.
A mutation in desmin makes skeletal muscle less vulnerable to acute muscle damage after eccentric loading in rats
(Wiley Open Access, 2021-09-01) Langer, Henning T.; Mossakowski, Agata A.; Avey, Alec M.; Wohlgemuth, Ross P.; Smith, Lucas R.; Zbinden-Foncea, Herman; Baar, Keith
Desminopathy is the most common intermediate filament disease in humans. The most frequent mutation causing desminopathy in patients is a R350P DES missense mutation. We have developed a rat model with an analogous mutation in R349P Des. To investigate the role of R349P Des in mechanical loading, we stimulated the sciatic nerve of wild-type littermates (WT) (n = 6) and animals carrying the mutation (MUT) (n = 6) causing a lengthening contraction of the dorsi flexor muscles. MUT animals showed signs of ongoing regeneration at baseline as indicated by a higher number of central nuclei (genotype: P < .0001). While stimulation did not impact central nuclei, we found an increased number of IgG positive fibers (membrane damage indicator) after eccentric contractions with both genotypes (stimulation: P < .01). Interestingly, WT animals displayed a more pronounced increase in IgG positive fibers with stimulation compared to MUT (interaction: P < .05). In addition to altered histology, molecular signaling on the protein level differed between WT and MUT. The membrane repair protein dysferlin decreased with eccentric loading in WT but increased in MUT (interaction: P < .05). The autophagic substrate p62 was increased in both genotypes with loading (stimulation: P < .05) but tended to be more elevated in WT (interaction: P = .05). Caspase 3 levels, a central regulator of apoptotic cell death, was increased with stimulation in both genotypes (stimulation: P < .01) but more so in WT animals (interaction: P < .0001). Overall, our data indicate that R349P Des rats have a lower susceptibility to structural muscle damage of the cytoskeleton and sarcolemma with acute eccentric loading.
Microencapsulated pomegranate peel extract induces mitochondrial complex IV activity and prevents mitochondrial cristae alteration in brown adipose tissue in mice fed on a high-fat diet
(Cambridge University Press, 2021-09-28) Echeverria, Francisca; Jimenez Patino, Paula; Castro-Sepulveda, Mauricio; Bustamante, Andres; Garcia Concha, Paula; Poblete-Aro, Carlos; Valenzuela, Rodrigo; Garcia-Diaz, Diego F
Pomegranate peel is an agro-industrial residue obtained after fruit processing with high total polyphenol (TP) content, making it an attractive by-product for its reuse. Pomegranate peel extract (PPE) and its bioactive compounds have shown positive effects on obesity models. Effects on favouring mitochondrial biogenesis and function have also been described. However, once phenolic compounds are extracted, their stability can be affected by diverse factors. Microencapsulation could improve PPE stability, allowing its incorporation into functional foods. Nevertheless, studies on the potential biological effects of PPE microparticles (MPPE) in obesity models are lacking. This study aims to evaluate the effect of MPPE on brown adipose tissue (BAT) mitochondrial structure and function and metabolic alterations related to obesity in mice fed a high-fat diet (HFD). PPE was microencapsulated by spray drying using inulin (IN) as a wall material and physically-chemically characterised. Eight-week-old male C57BL/6J mice (n 40) were randomly distributed into five groups: control diet (CD), HFD, HFD + IN, HFD + PPE (50 mg/kg per d TP) and HFD + MPPE (50 mg/kg per d TP), for 14 weeks. A glucose tolerance test and indirect calorimetry were conducted. Blood and adipose tissue samples were obtained. MPPE supplementation prevented HFD-induced body weight gain (P < 0·001), fasting glycaemia (P = 0·007) and total cholesterol rise (P = 0·001). MPPE resulted in higher BAT mitochondrial complex IV activity (P = 0·03) and prevented HFD-induced mitochondrial cristae alteration (P = 0·02). In conclusion, MPPE prevented HFD-induced excessive body weight gain and associated metabolic disturbances, potentially by activating complex IV activity and preserving mitochondrial cristae structure in BAT in mice fed with a HFD.
Low abundance of Mfn2 protein correlates with reduced mitochondria-SR juxtaposition and mitochondrial cristae density in human men skeletal muscle: Examining organelle measurements from TEM images
(Wiley Open Access, 2021-04-04) Castro-Sepulveda, Mauricio; Fernández-Verdejo, Rodrigo; Tuñón-Suárez, Mauro; Morales-Zúñiga, Jorge; Troncoso, Mayarling; Jannas-Vela, Sebastian; Zbinden-Foncea, Hermann
The role of mitofusin 2 (Mfn2) in the regulation of skeletal muscle (SM) mitochondria-sarcoplasmic (SR) juxtaposition, mitochondrial morphology, mitochondrial cristae density (MCD), and SM quality has not been studied in humans. In in vitro studies, whether Mfn2 increases or decreases mitochondria-SR juxtaposition remains controversial. Transmission electron microscopy (TEM) images are commonly used to measure the organelle juxtaposition, but the measurements are performed "by-hand," thus potentially leading to between-rater differences. The purposes of this study were to: (1) examine the repeatability and reproducibility of mitochondrial-SR juxtaposition measurement from TEM images of human SM between three raters with different experience and (2) compare the mitochondrial-SR juxtaposition, mitochondrial morphology, MCD (stereological-method), and SM quality (cross-sectional area [CSA] and the maximum voluntary contraction [MVC]) between subjects with high abundance (Mfn2-HA; n = 6) and low abundance (Mfn2-LA; n = 6) of Mfn2 protein. The mitochondria-SR juxtaposition had moderate repeatability and reproducibility, with the most experienced raters showing the best values. There were no differences between Mfn2-HA and Mfn2-LA groups in mitochondrial size, distance from mitochondria to SR, CSA, or MVC. Nevertheless, the Mfn2-LA group showed lower mitochondria-SR interaction, MCD, and VO2max . In conclusion, mitochondrial-SR juxtaposition measurement depends on the experience of the rater, and Mfn2 protein seems to play a role in the metabolic control of human men SM, by regulating the mitochondria-SR interaction.
The fasting-feeding metabolic transition regulates mitochondrial dynamics
(Federation of American Society of Experimental Biology (FASEB), 2021-10-10) Castro-Sepulveda, Mauricio; Morio, Béatrice; Tuñón-Suárez, Mauro; Jannas-Vela, Sebastian; Díaz-Castro, Francisco; Rieusset, Jennifer; Zbinden-Foncea, Hermann
In humans, insulin resistance has been linked to an impaired metabolic transition from fasting to feeding (metabolic flexibility; MetFlex). Previous studies suggest that mitochondrial dynamics response is a putative determinant of MetFlex; however, this has not been studied in humans. Thus, the aim of this study was to investigate the mitochondrial dynamics response in the metabolic transition from fasting to feeding in human peripheral blood mononuclear cells (PBMCs). Six male subjects fasted for 16 h (fasting), immediately after which they consumed a 75-g oral glucose load (glucose). In both fasting and glucose conditions, blood samples were taken to obtain PBMCs. Mitochondrial dynamics were assessed by electron microscopy images. We exposed in vitro acetoacetate-treated PBMCs to the specific IP3R inhibitor Xestospongin B (XeB) to reduce IP3R-mediated mitochondrial Ca2+ accumulation. This allowed us to evaluate the role of ER-mitochondria Ca2+ exchange in the mitochondrial dynamic response to substrate availability. To determine whether PBMCs could be used in obesity context (low MetFlex), we measured mitochondrial dynamics in mouse spleen-derived lymphocytes from WT and ob/ob mice. We demonstrated that the transition from fasting to feeding reduces mitochondria-ER interactions, induces mitochondrial fission and reduces mitochondrial cristae density in human PBMCs. In addition, we demonstrated that IP3R activity is key in the mitochondrial dynamics response when PBMCs are treated with a fasting-substrate in vitro. In murine mononuclear-cells, we confirmed that mitochondria-ER interactions are regulated in the fasted-fed transition and we further highlight mitochondria-ER miscommunication in PBMCs of diabetic mice. In conclusion, our results demonstrate that the fasting/feeding transition reduces mitochondria-ER interactions, induces mitochondrial fission and reduces mitochondrial cristae density in human PBMCs, and that IP3R activity may potentially play a central role.
Association between adipose tissue characteristics and metabolic flexibility in humans: A systematic review
(Frontiers Media, 2021-12-03) Glaves, Alice; Díaz-Castro, Francisco; Farías, Javiera; Ramírez-Romero, Rodrigo; Galgan, Jose E.; Fernández-Verdejo, Rodrigo
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
Similar metabolic health in overweight/obese individuals with contrasting metabolic flexibility to an oral glucose tolerance test
(Frontiers Media, 2021-11-16) Fernández-Verdejo, Rodrigo; Malo-Vintimilla, Lorena; Gutiérrez-Pino, Juan; López-Fuenzalida, Antonio; Olmos, Pablo; Irarrazaval, Pablo; Galgani, Jose E.
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; 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.

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