Optimizing Maximal Fat Oxidation Assessment by a Treadmill-Based Graded Exercise Protocol: When Should the Test End?

Maximal fat oxidation during exercise (MFO) and the exercise intensity eliciting MFO (Fatmax) are considered important factors related to metabolic health and performance. Numerous MFO and Fatmax data collection and analysis approaches have been applied, which may have influenced their estimation during an incremental graded exercise protocol. Despite the heterogeneity of protocols used, all studies consistently stopped the MFO and Fatmax test when the respiratory exchange ratio (RER) was 1.0. It remains unknown however whether reaching a RER of 1.0 is required to have an accurate, reliable, and valid measure of MFO and Fatmax. We aimed to investigate the RER at which MFO and Fatmax occurred in sedentary and trained healthy adults. A total of 166 sedentary adults aged between 18 and 65 years participated in the study. MFO and Fatmax were calculated by an incremental graded exercise protocol before and after two exercise-based interventions. Our findings suggest that a graded exercise protocol aiming to determine MFO and Fatmax could end when a RER = 0.93 is reached in sedentary healthy adults, and when a RER = 0.90 is reached in trained adults independently of sex, age, body weight status, or the Fatmax data analysis approach. In conclusion, we suggest reducing the RER from 1.0 to 0.95 to be sure that MFO is reached in outliers. This methodological consideration has important clinical implications, since it would allow to apply smaller workload increments and/or to extend the stage duration to attain the steady state, without increasing the test duration.This study was supported by the Spanish Ministry of Economy and Competitiveness via the Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (PI13/01393), Retos de la Sociedad (DEP2016-79512-R) and European Regional Development Funds (ERDF), the Spanish Ministry of Education (FPU 13/04365, FPU14/04172), the Spanish Ministry of Education and Science (Red EXERNET DEP2005-00046), the Fundación Iberoamericana de Nutrición (FINUT), the Redes Temáticas de Investigación Cooperativa RETIC (Red SAMID RD16/0022), the AstraZeneca HealthCare Foundation, the University of Granada Plan Propio de Investigación 2016 – Excellence actions: Unit of Excellence on Exercise and Health (UCEES) – and Plan Propio de Investigación 2018 – Programa Contratos-Puente, and the Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades (ERDF: ref. SOMM17/6107/UGR)

A Systematic Review and Meta-Analysis on the Association and Differences between Aerobic Threshold and Point of Optimal Fat Oxidation

Over the past two decades, scientists have attempted to evaluate whether the point of maximal fat oxidation (FATmax) and the aerobic threshold (AerT) are connected. The existence of such a relationship would allow a more tailored training approach for athletes while improving the efficacy of individualized exercise prescriptions when treating numerous health-related issues. However, studies have reported conflicting results, and this issue remains unresolved. This systematic review and meta-analysis aimed: (i) to examine the strength of the association between FATmax and AerT by using the effect size (ES) of correlation coefficient (r) and standardized mean difference (SMD); (ii) to identify potential moderators and their influence on ES variability. This study was registered with PROSPERO (CRD42021239351) and ClinicalTrials (NCT03789045). PubMed and Google Scholar were searched and fourteen articles, consisting of overall 35 ES for r and 26 ES for SMD were included. Obtained ESs were analyzed using a multilevel random-effects meta-analysis. Our results support the presence of a significant association between FATmax and AerT exercise intensities. In conclusion, due to the large ES variance caused by clinical and methodological differences among the studies, we recommend that future studies follow strict standardization of data collection and analysis of FATmax and AerT-related outcomes

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Premio extraordinario de Trabajo Fin de Máster curso 2018/2019. Máster en Profesorado de Enseñanza Secundaria Obligatoria, Bachillerato, Formación Profesional y Enseñanza de Idioma

Synthesis, characterization and applications of materials with hybrid nature

La presente Tesis Doctoral aborda la síntesis, funcionalización, caracterización y aplicaciones de una extensa variedad de materiales híbridos orgánico-inorgánicos. Los resultados obtenidos en esta investigación han sido clasificados en tres secciones atendiendo a la naturaleza híbrida del material diseñado: • Sección 1: Polímeros de coordinación-Metal Organic Frameworks (MOFs): ▪ En el artículo “Zirconium coordination polymers based on tartaric and malic acids as catalysts for cyanosilylation reactions” se han sintetizado polímeros de coordinación que contienen zirconio como nodo metálico y ligandos orgánicos procedentes de productos naturales sencillos que contienen centros quirales como son el ácido L-málico, L-tartárico y dibenzoil-L-tartárico. Los materiales fueron preparados en autoclave bajo presión autógena o en reactor tipo batch bajo presión atmosférica. Tras ser caracterizados por diferentes técnicas, se han evaluado como catalizadores heterogéneos quirales en la reacción asimétrica de cianosililación del benzaldehído con cianuro de trimetilsililo dando como resultado la formación de cianohidrinas. La actividad catalítica en términos de conversión y enantioselectividad fue determinada estudiando el efecto de diferentes variables de reacción como la temperatura, el disolvente, la adición de promotores o el sustrato empleado. ▪ En el artículo “Fast ultrasound-assisted synthesis of highly crystalline MIL-88A particles and their application as ethylene adsorbents” se han sintetizado partículas altamente cristalinas del MOF MIL-88A compuesto por trímeros de octaedros de hierro (III) interconectados a través de dianiones fumarato mediante una metodología rápida asistida por ultrasonidos. La influencia del generador de sonicación y el tiempo de síntesis en la estructura, cristalinidad, morfología y el área superficial fue estudiada detalladamente. Además, los materiales preparados han sido aplicados en procesos de adsorción de etileno. Estos resultados fueron comparados con los obtenidos por otros MOFs comunes ampliamente reportados en literatura. ▪ El artículo “MIL-88A Metal-Organic Framework as a stable sulfur-host cathode for long-cycle Li-S batteries” estuvo en consonancia con el trabajo anterior. Aprovechando las propiedades texturales y morfológicas de las partículas MIL-88A sintetizadas mediante el método de sonda asistida por ultrasonidos en un corto tiempo de 10 minutos, este material fue empleado como anfitrión para la impregnación de azufre con objeto de ser usado como componente catódico en baterías Litio Azufre (Li-S), uno de los sistemas más avanzados de almacenamiento de energía. Además, la estabilidad del sistema electroquímico resultante fue evaluada llevando a cabo experimentos de ciclabilidad a tiempos prolongados. • Sección 2: Materiales híbridos orgánico-inorgánicos basados en sílice-Periodic Mesoporous Organosilicas (PMOs): ▪ El artículo “Catalytic systems mimicking the [FeFe]- hydrogenase active site for visible-light-driven hydrogen production” consistió en una revisión exhaustiva que abordó el campo de la química biomimética de los sistemas catalíticos que imitan el sitio activo de [FeFe]-hidrogenasa aplicados en la producción de hidrógeno dirigida por luz. Los diferentes sistemas fotocatalíticos fueron clasificados por grupos en orden de complejidad creciente y por su desarrollo cronológico: catalizadores moleculares [2Fe2S], díadas de fotosensibilizador - [FeFe]-hidrogenasa, tríadas de donador de electrones - fotosensibilizador - [FeFe]-hidrogenasa, entidades supramoleculares, conjuntos de semiconductores híbridos, soportes heterogéneos y fotocátodos basados en [2Fe2S] para dispositivos fotoelectroquímicos (PEC). ▪ El artículo de revisión citado anteriormente sirvió para llevar a cabo el trabajo “Hydroxyl-decorated diiron complex as a [FeFe]-hydrogenase active site model complex: Light-driven photocatalytic activity and heterogenization on ethylene-bridged periodic mesoporous organosilica” en que un complejo modelo biomimético del sitio activo de [FeFe]-hidrogenasa (FeFeOH) con un puente de etileno y un grupo hidroxilo colgante fue sintetizado y caracterizado detalladamente. La interacción del grupo hidroxilo presente en el complejo con 3- isocianatopropiltrietoxisilano proporcionó un carbamato trietoxisilano portador de un complejo ditiolato de dihierro (NCOFeFe), convirtiéndose así en un precursor potencialmente prometedor para su anclaje sobre soportes heterogéneos. A continuación, el precursor NCOFeFe fue incorporado mediante un procedimiento de “grafting” en una organosílice periódica mesoporosa con puentes etano (EthanePMO@NCOFeFe). Adicionalmente, tanto los complejos moleculares como los heterogeneizados se evaluaron como catalizadores para la generación de hidrógeno en solución acuosa impulsada por la luz, optimizando todas las condiciones fotocatalíticas: tiempo de reacción, pH, cantidad de catalizador o fotosensibilizador, flujo de fotones y tipo de fuente de luz (LED y lámpara Xe). • Sección 3: Materiales híbridos basados en grafeno: ▪ En el artículo “A comparative study of particle size distribution of graphene nanosheets synthesized by an ultrasound-assisted method” se han preparado nanoláminas de grafeno (GNS) mediante la exfoliación de un micrografito comercial (MG) utilizando una sonda de ultrasonido. La caracterización estructural, superficial y morfológica fue realizada por difracción de rayos X (DRX), espectroscopia Raman, espectroscopia de fotoelectrones de rayos X (XPS) y microscopía electrónica de transmisión (TEM). Un estudio exhaustivo de la distribución del tamaño de partícula se llevó a cabo mediante diferentes técnicas analíticas como la dispersión de luz dinámica (DLS), análisis de seguimiento de nanopartículas (NTA) y fraccionamiento en flujo mediante campo de flujo asimétrico (AF4). ▪ En el artículo “Luminescent graphene-based materials via europium complexation on dipyridylpyridazine-functionalized graphene sheets” se sintetizaron materiales híbridos basados en grafeno mediante reacciones Diels-Alder entre grafito (dienófilo) y la molécula orgánica 3,6-di(2-piridil)-1,2,4,5-tetrazina (dieno). Se obtuvieron grafeno de pocas capas (FLG), grafeno multicapa (MLG) y grafito (MG) funcionalizados con unidades de dipiridilpiridazina dependiendo de la metodología de síntesis aplicada. Los aductos superficiales de dipiridilpiridazina generados en las láminas de grafeno han sido empleados para la formación de complejos de europio, como ejemplos de iones lantánidos emisores en el visible. ▪ En el artículo “Surface Diels-Alder adducts on multilayer graphene for the generation of edge-enriched single-atom FeN4 sites for ORR and OER electrocatalysis” se propone una nueva síntesis mecanoquímica a baja temperatura y sin disolventes basada en el uso de grafeno multicapa funcionalizado con dipiridilpiridazina como material de partida para la generación de sitios activos de tipo FeN4. Después de una caracterización exhaustiva, estos materiales fueron aplicados como electrocatalizadores bifuncionales para reacciones electroquímicas de reducción de oxígeno (ORR) y evolución de oxígeno (OER).This Doctoral Thesis deals with the synthesis, functionalization, characterization, and applications of a wide variety of organic-inorganic hybrid materials. The results obtained in this research have been divided into three sections according to the hybrid nature of the designed material: • Section 1: Coordination Polymers-Metal Organic Frameworks (MOFs): ▪ In the article “Zirconium coordination polymers based on tartaric and malic acids as catalysts for cyanosilylation reactions”, coordination polymers containing zirconium as a metallic node and organic ligands from simple natural products containing chiral centers such as L-malic, L-tartaric and dibenzoyl-L-tartaric acids, have been synthesized. The materials were prepared in an autoclave under autogenous pressure or in a batch type reactor under atmospheric pressure. After being characterized by different techniques, they have been evaluated as chiral heterogeneous catalysts in the asymmetric cyanosilylation reaction of benzaldehyde with trimethylsilyl cyanide, resulting in the formation of cyanohydrins. The catalytic activity in terms of conversion and enantioselectivity was determined by studying the effect of different reaction parameters such as temperature, solvent, the addition of promoters or the substrate used. ▪ In the article “Fast ultrasound-assisted synthesis of highly crystalline MIL-88A particles and their application as ethylene adsorbents”, highly crystalline particles of the MOF MIL-88A composed of trimers of iron (III) octahedrons interconnected through fumarate dianions have been synthesized by a fast ultrasound-assisted methodology. The influence of the sonication generator and the synthesis time on the structure, crystallinity, morphology and surface area was studied in detail. In addition, the prepared materials have been applied in ethylene adsorption processes. These results were compared with those obtained by other common MOFs widely reported in the literature. ▪ The article “MIL-88A Metal-Organic Framework as a stable sulfur-host cathode for long-cycle Li-S batteries” was consistent with the previous work. Taking advantage of the textural and morphological properties of the MIL-88A particles synthesized by the ultrasound-assisted probe method in a short time of 10 minutes, this material was used as a sulfur host to be applied as a cathode component in Lithium-Sulfur (Li-S) batteries, one of the most advanced energy storage systems. In addition, the stability of the resulting electrochemical system was evaluated by carrying out long-term cyclability experiments. • Section 2: Silica-based organic-inorganic hybrid materials-Periodic Mesoporous Organosilicas (PMOs): ▪ The article “Catalytic systems mimicking the [FeFe]- hydrogenase active site for visible-light-driven hydrogen production” was an exhaustive review that addressed the field of biomimetic chemistry of catalytic systems mimicking the active site of [FeFe]-hydrogenase applied in the light-driven hydrogen production. The different photocatalytic systems were classified by groups in order of increasing complexity and by their chronological development: [2Fe2S] molecular catalysts, photosensitizer-[FeFe]-hydrogenase dyads, electron donor photosensitizer-[FeFe]-hydrogenase triads, supramolecular entities, hybrid semiconductor arrays, heterogeneous supports and [2Fe2S]-based photocathodes for photoelectrochemical (PEC) devices. ▪ The review article cited above served to carry out the work “Hydroxyl-decorated diiron complex as a [FeFe]-hydrogenase active site model complex: Light-driven photocatalytic activity and heterogenization on ethylene-bridged periodic mesoporous organosilica” in which a biomimetic model complex for the [FeFe]-hydrogenase active site (FeFeOH) with an ethylene bridge and a pendant hydroxyl group was synthesized and characterized in detail. The reaction of the hydroxyl group present in the complex with 3-isocyanatopropyltriethoxysilane provided a triethoxysilane carbamate bearing a complex diiron dithiolate (NCOFeFe), thus becoming a potentially promising precursor for its anchoring on heterogeneous supports. Next, the precursor NCOFeFe was incorporated by a "grafting" procedure in a periodic mesoporous organosilica with ethane bridges (EthanePMO@NCOFeFe). Additionally, both molecular and heterogenized complexes were evaluated as catalysts for hydrogen evolution reactions in aqueous solution assisted by visible light, optimizing all the photocatalytic conditions: reaction time, pH, amount of catalyst or photosensitizer, photon flux and light source (LED and Xe lamp). • Section 3: Graphene-based hybrid materials: ▪ In the article “A comparative study of particle size distribution of graphene nanosheets synthesized by an ultrasound-assisted method”, graphene nanosheets (GNS) have been prepared by exfoliating a commercial micrographite (MG) using an ultrasound probe. Structural, surface, and morphological characterization was performed by X-ray diffraction (XRD), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM). An exhaustive study of the particle size distribution was carried out using different analytical techniques such as dynamic light scattering (DLS), nanoparticle tracking analysis (NTA) and asymmetrical flow field - flow fractionation (AF4). ▪ In the article “Luminescent graphene-based materials via europium complexation on dipyridylpyridazine-functionalized graphene sheets”, graphene-based hybrid materials were synthesized by Diels-Alder reactions between graphite (dienophile) and the organic molecule 3,6-di(2-pyridyl)- 1,2,4,5- tetrazine (diene). Few layer graphene (FLG), multilayer graphene (MLG) and graphite (MG) functionalized with dipyridylpyridazine units were obtained depending on the synthesis methodology applied. Surface adducts of dipyridylpyridazine generated in graphene sheets have been used for the formation of europium complexes, as examples of emitting lanthanide ions in the visible. ▪ The article “Surface Diels-Alder adducts on multilayer graphene for the generation of edge-enriched single-atom FeN4 sites for ORR and OER electrocatalysis” proposes a new mechanochemical synthesis at low temperature and without solvents based on the use of multilayer graphene functionalized with dipyridylpyridazine as starting material for the generation of FeN4-type active sites. After extensive characterization, these materials were applied as bifunctional electrocatalysts for electrochemical oxygen reduction (ORR) and oxygen evolution (OER) reactions

Editorial: Functional fitness/high intensity functional training for health and performance

Functional fitness training (FFT) is an emerging fitness trend that emphasizes functional, multi-joint movements, including aerobic (e.g., cycling, rowing, running) and strength exercises (e.g., weightlifting and derivatives: squat, snatch, clean and jerk, bench press, deadlift; bodyweight exercises: air squat, push-up, pull-up, muscle-up; plyometrics: box jumps, tuck ups) (Claudino et al., 2018; Feito et al., 2018). Researchers have shown that FFT may be not only suitable for professional athletes but also for populations with different fitness levels. Indeed, it is suggested that FFT elicits greater muscle recruitment than aerobic exercises alone, thereby improving both endurance and muscular strength and power (Bergeron et al., 2011; Claudino et al., 2018; Feito et al., 2018; Schlegel, 2020; Sharp et al., 2022). However, FFT units (i.e., workouts) are highly varied daily, and more research is needed to clarify its acute effects and its associated chronic training adaptations (Bergeron et al., 2011; Claudino et al., 2018; Feito et al., 2018; Schlegel, 2020; Sharp et al., 2022). Therefore, the aim of this Research Topic is to increase the knowledge of the evidence-based effects and adaptations of implementing FFT on health and performance in individuals with different biological conditions

Effect of p-Synephrine on Fat Oxidation Rate during Exercise of Increasing Intensity in Healthy Active Women

p-Synephrine is the principal alkaloid of bitter orange (Citrus aurantium). Several recent investigations have found that the intake of 2-3 mg/kg of p-synephrine raises fat oxidation rate during exercise of low-to-moderate intensity. However, these investigations have been carried out only with samples of male participants or mixed men/women samples. Therefore, the aim of this investigation was to study the effect of p-synephrine intake on fat oxidation during exercise of increasing intensity in healthy women. Using a double-blind, randomized experiment, 18 healthy recreationally active women performed two identical exercise trials after the ingestion of (a) 3 mg/kg of p-synephrine and (b) 3 mg/kg of a placebo (cellulose). The exercise trials consisted of a ramp test (from 30 to 80% of maximal oxygen uptake; VO(2)max) on a cycle ergometer while substrate oxidation rates were measured at each workload by indirect calorimetry. In comparison to the placebo, the intake of p-synephrine increased resting tympanic temperature (36.1 +/- 0.5 vs. 36.4 +/- 0.4 degrees C p = 0.033, d = 0.87) with no effect on resting heart rate (p = 0.111) and systolic (p = 0.994) and diastolic blood pressure (p = 0.751). During exercise, there was no significant effect of p-synephrine on fat oxidation rate (F = 0.517; p = 0.484), carbohydrate oxidation rate (F = 0.730; p = 0.795), energy expenditure rate (F = 0.480; p = 0.833), heart rate (F = 4.269; p = 0.068) and participant's perceived exertion (F = 0.337; p = 0.580). The maximal rate of fat oxidation with placebo was 0.26 +/- 0.10 g/min and it was similar with p-synephrine (0.28 +/- 0.08 g/min, p = 0.449, d = 0.21). An acute intake of 3 mg/kg of p-synephrine before exercise did not modify energy expenditure and substrate oxidation during submaximal aerobic exercise in healthy active women. It is likely that the increase in resting tympanic temperature induced by p-synephrine hindered the effect of this substance on fat utilization during exercise in healthy active women.Francisco de Vitoria University UFV-18/202

Factors Determining the Agreement between Aerobic Threshold and Point of Maximal Fat Oxidation: Follow-Up on a Systematic Review and Meta-Analysis on Association

Regular exercise at the intensity matching maximal fat oxidation (FATmax) has been proposed as a key element in both athletes and clinical populations when aiming to enhance the body’s ability to oxidize fat. In order to allow a more standardized and tailored training approach, the connection between FATmax and the individual aerobic thresholds (AerT) has been examined. Although recent findings strongly suggest that a relationship exists between these two intensities, correlation alone is not sufficient to confirm that the intensities necessarily coincide and that the error between the two measures is small. Thus, this systematic review and meta-analysis aim to examine the agreement levels between the exercise intensities matching FATmax and AerT by pooling limits of agreement in a function of three parameters: (i) the average difference, (ii) the average within-study variation, and (iii) the variation in bias across studies, and to examine the influence of clinical and methodological inter- and intra-study differences on agreement levels. This study was registered with PROSPERO (CRD42021239351) and ClinicalTrials (NCT03789045). PubMed and Google Scholar were searched for studies examining FATmax and AerT connection. Overall, 12 studies with forty-five effect sizes and a total of 774 subjects fulfilled the inclusion criteria. The ROBIS tool for risk of bias assessment was used to determine the quality of included studies. In conclusion, the overall 95% limits of agreement of the differences between FATmax and AerT exercise intensities were larger than the a priori determined acceptable agreement due to the large variance caused by clinical and methodological differences among the studies. Therefore, we recommend that future studies follow a strict standardization of data collection and analysis of FATmax- and AerT-related outcomes

Does the Time of Day Play a Role in the Acute Effect of p-Synephrine on Fat Oxidation Rate during Exercise in Women? A Randomized, Crossover and Double-Blind Study

p-Synephrine is deemed a safe and effective substance to increase fat utilization during exercise of low-to-moderate intensity in men but not in women. Additionally, the existence of a diurnal variation in substrate utilization has been documented during exercise with enhanced fat oxidation in the evening compared with early morning. However, it remains unknown whether there is an interaction between the effect of p-synephrine and the time of the day on fat oxidation during exercise. This study aimed to evaluate the effect of the acute ingestion of 3 milligram of p-synephrine per kilogram of body mass (mg/kg) on fat oxidation during exercise of increasing intensity when the exercise is performed in the morning vs. the evening. Using a randomized, double-blind, placebo-controlled experimental design, 16 healthy and active women performed four identical exercise trials after the ingestion of 3 mg/kg of p-synephrine and 3 mg/kg of a placebo (cellulose) both in the morning (8-10 am) and in the evening (5-7 pm). In the exercise trials, the substances were ingested 60 min before an incremental test on a cycle ergometer with 3 min stages at workloads from 30 to 80% of maximal oxygen uptake (VO(2)max). Substrate oxidation rates were measured by indirect calorimetry. In each trial, the maximum rate of fat oxidation (MFO) and the intensity that elicited MFO (Fatmax) were measured. A two-way analysis of variance (time-of-the day x substance) was used to detect differences among the trials. With the placebo, MFO was 0.25 +/- 0.11 g/min in the morning and 0.24 +/- 0.07 g/min in the evening. With p-synephrine, MFO was 0.26 +/- 0.09 g/min in the morning and 0.21 +/- 0.07 g/min in the evening. There was no main effect of substance (p = 0.349), time of day (p = 0.186) and the substance x time of day (p = 0.365) on MFO. Additionally, Fatmax was reached at a similar exercise intensity with the placebo (41.33 +/- 8.34% VO(2)max in the morning and 44.38 +/- 7.37% VO(2)max in the evening) and with p-synephrine (43.33 +/- 7.24% VO(2)max in the morning and 45.00 +/- 7.43% VO(2)max in the evening), irrespective of the time of day with no main effect of substance (p = 0.633), time of day (p = 0.191), or interaction (p = 0.580). In summary, the acute intake of 3 mg/kg of p-synephrine before exercise did not increase MFO and Fatmax, independently of the time of day, in female athletes. This indicates that the time of day is not a factor explaining the lack of effectiveness of this substance to enhance fat oxidation during aerobic exercise in women.Francisco de Vitoria University, grant number UFV-18/202

Dietary Inflammatory Index and S-Klotho Plasma Levels in Middle-Aged Adults

Background: Soluble Klotho (S-Klotho) is an aging suppressor with a close link with inflammation. However, it is still unknown whether the dietary inflammatory potential is associated with S-Klotho plasma level. We aimed to investigate the association of the Dietary Inflammatory Index (DII) with S-Klotho plasma levels in middle-aged sedentary adults. Methods: 73 middle-aged sedentary adults (40–65 years old) participated in the present study. DII was determined from 28 dietary items obtained by 24 h recalls and food frequency questionnaires. The S-Klotho plasma levels were measured using a solid-phase sandwich enzyme-linked immunosorbent assay. Results: a weak positive association was observed between DII and S-Klotho plasma levels ( B = 52.223, R2 = 0.057, p = 0.043), which disappeared after controlling for body mass index (p = 0.057). Conclusions: A pro-inflammatory dietary pattern measured with the DII was slightly and positively associated with S-Klotho plasma levels in middle-aged sedentary adults.The study was supported by the Spanish Ministry of Education (FPU14/04172 and FPU15/03960), by the University of Granada UGR Research and Knowledge Transfer Fund (PPIT) 2016 (Excellence Actions Programme. Units of Scientific Excellence: Scientific Unit of Excellence on Exercise and Health [UCEES]), by the Regional Government of Andalusia, Regional Ministry of Economy, Knowledge, Enterprises and University, by the European Regional Development Fund (ERDF), ref. SOMM17/6107/UGR and by Redes Temáticas de Investigación Cooperativa RETIC grant Red SAMID RD16/0022