Loss of Bone Mineral Density Associated with Age in Male Rats Fed on Sunflower Oil Is Avoided by Virgin Olive Oil Intake or Coenzyme Q Supplementation

The role of dietary fat unsaturation and the supplementation of coenzyme Q have been evaluated in relation to bone health. Male Wistar rats were maintained for 6 or 24 months on two diets varying in the fat source, namely virgin olive oil, rich in monounsaturated fatty acids, or sunflower oil, rich in n-6 polyunsaturated fatty acids. Both dietary fats were supplemented or not with coenzyme Q10 (CoQ10). Bone mineral density (BMD) was evaluated in the femur. Serum levels of osteocalcin, osteopontin, receptor activator of nuclear factor κB ligand (RANKL), osteoprotegerin (OPG), adrenocorticotropin (ACTH) and parathyroid hormone (PTH), as well as urinary F2-isoprostanes were measured. Aged animals fed on virgin olive oil showed higher BMD than those fed on sunflower oil. In addition, CoQ10 prevented the age-related decline in BMD in animals fed on sunflower oil. Urinary F2-isoprostanes analysis showed that sunflower oil led to the highest oxidative status in old animals, which was avoided by supplementation with CoQ10. In conclusion, lifelong feeding on virgin olive oil or the supplementation of sunflower oil on CoQ10 prevented, at least in part mediated by a low oxidative stress status, the age-related decrease in BMD found in sunflower oil fed animals.This work was supported by the Spanish Ministry of Education and Science (AGL2008-01057) and the Autonomous Government of Andalusia (AGR832)

Evaluación de la fertilización nitrogenada sobre la producción y el valor nutritivo de Setaria sphacelata cv. Narok

Con el objeto de evaluar la productividad y el contenido de Proteína Bruta, Fibra Detergente Neutra y Ácida de Setaria sphacelata cv. Narok con diferentes tratamientos de fertilización nitrogenada, se realizó un ensayo sobre una pastura implantada en la EEA INTA Colonia Benítez. El diseño fue DBCA y los tratamientos T0=sin fertilización, T1=100, T2=200, T3=300 y T4=400 Kg de N ha-1, y 4 repeticiones. Los bloques correspondieron a cada una de las siete fechas de cortes. Los cortes se realizaron cada 40 días, a partir del corte de emparejamiento. Las muestras fueron procesadas en la Facultad de Ciencias Agrarias, determinando la producción de materia seca (PMS), proteína bruta (PB), fibra detergente neutra (FDN) y ácida (FDA). La PMS acumulada presentó interacción entre fechas de corte y tratamientos de fertilización. El efecto de la fertilización fue más manifiesto durante los meses de mayor crecimiento acompañado por las altas precipitaciones. La PB fue mayor en los primeros cortes. T3 y T4 tuvieron los mayores porcentajes de PB, particularmente en el primer y segundo corte. La FDN, presentó diferencias entre T0 (64,32%) y los tratamientos fertilizados (58,14%) sólo en el segundo corte. La FDA no presentó diferencias en los dos primeros cortes, y sí hubo en enero entre T0 (35,47%) y el resto (42,32%). Concluyendo, la fertilización nitrogenada incrementó la PMS. La PB fue la más afectada con el agregado del fertilizante nitrogenado. FDN y FDA no evidenciaron cambios con la fertilización nitrogenada

Fecal microbiota composition is related to brown adipose tissue 18F‑fluorodeoxyglucose uptake in young adults

Objective Human brown adipose tissue (BAT) has gained considerable attention as a potential therapeutic target for obesity and its related cardiometabolic diseases; however, whether the gut microbiota might be an efficient stimulus to activate BAT metabolism remains to be ascertained. We aimed to investigate the association of fecal microbiota composition with BAT volume and activity and mean radiodensity in young adults. Methods 82 young adults (58 women, 21.8 ± 2.2 years old) participated in this cross-sectional study. DNA was extracted from fecal samples and 16S rRNA sequencing was performed to analyse the fecal microbiota composition. BAT was determined via a static 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography scan (PET/CT) after a 2 h personalized cooling protocol. 18F-FDG uptake was also quantified in white adipose tissue (WAT) and skeletal muscles. Results The relative abundance of Akkermansia, Lachnospiraceae sp. and Ruminococcus genera was negatively correlated with BAT volume, BAT SUVmean and BAT SUVpeak (all rho ≤ − 0.232, P ≤ 0.027), whereas the relative abundance of Bifidobacterium genus was positively correlated with BAT SUVmean and BAT SUVpeak (all rho ≥ 0.262, P ≤ 0.012). On the other hand, the relative abundance of Sutterellaceae and Bifidobacteriaceae families was positively correlated with 18FFDG uptake by WAT and skeletal muscles (all rho ≥ 0.213, P ≤ 0.042). All the analyses were adjusted for the PET/CT scan date as a proxy of seasonality. Conclusion Our results suggest that fecal microbiota composition is involved in the regulation of BAT and glucose uptake by other tissues in young adults. Further studies are needed to confirm these findings.Universidad de Granada / CBUASpanish Ministry of Economy and Competitiveness via Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III PI13/01393 PTA 12264-IRetos de la Sociedad DEP2016-79512-REuropean Commission Spanish Government FPU13/04365 FPU16/05159 FPU17/01523Fundacion Iberoamericana de Nutricion (FINUT)Redes Tematicas De Investigacion Cooperativa RETIC Red SAMID RD16/0022InFLAMES Flagship Programme of the Academy of Finland 337530NextGenerationEU RR_C_2021_04AstraZenecaUniversity of Granada Plan Propio de Investigacion 2016-Excellence actions: Unit of Excellence on Exercise and Health (UCEES)Junta de Andalucia, Consejeria de Conocimiento, Investigacion y Universidades (ERDF) SOMM17/6107/UGREuropean Commission through the "European funds for regional development" (EFRE)regional Ministry of Economy, Science and Digitalization of Saxony-Anhalt as part of the "Autonomy in old Age"(AiA) research group for "LiLife" Project ZS/2018/11/95324MIRACUMFederal Ministry of Education & Research (BMBF) FKZ 01ZZ1801HFundacion Alfonso Martin Escuder

The impact of using BARCIST 1.0 criteria on quantification of BAT volume and activity in three independent cohorts of adults

Human brown adipose tissue (BAT) is commonly assessed by cold-induced 18F-fluorodeoxyglucose (FDG) PET-CT using several quantification criteria. Uniform criteria for data analysis became available recently (BARCIST 1.0). We compared BAT volume and activity following BARCIST 1.0 criteria against the most commonly used criteria [Hounsfield Units (HU):-250, -50, standardized uptake value (SUV):2.0; HU: Not applied, SUV:2.0 and HU:-180, -10, SUV:1.5] in a prospective study using three independent cohorts of men including young lean adults, young overweight/obese adults and middle-aged overweight/obese adults. BAT volume was the most variable outcome between criteria. While BAT volume calculated using the HU: NA; SUV: 2.0 criteria was up to 207% higher than the BAT volume calculated based on BARCIST 1.0 criteria, it was up to 57% lower using the HU: -250, -50; SUV: 2.0 criteria compared to the BARCIST 1.0. Similarly, BAT activity (expressed as SUVmean) also differed between different thresholds mainly because SUVmean depends on BAT volume. SUVpeak was the most consistent BAT outcome across the four study criteria. Of note, we replicated these findings in three independent cohorts. In conclusion, BAT volume and activity as determined by 18F-FDG-PET/CT highly depend on the quantification criteria used. Future human BAT studies should conduct sensitivity analysis with different thresholds in order to understand whether results are driven by the selected HU and/or SUV thresholds. The design of the present study precludes providing any conclusive threshold, but before more definitive thresholds for HU and SUV are available, we support the use of BARCIST 1.0 criteria to facilitate interpretation of BAT characteristics between research groups

The value of metabolic imaging to predict tumour response after chemoradiation in locally advanced rectal cancer

Preliminary data of this work were presented by RCM and awarded at the 2009 Annual Meeting of the Spanish Society of Coloproctology (AECP) held in Barcelona.Background: We aim to investigate the possibility of using 18F-positron emission tomography/computer tomography (PET-CT) to predict the histopathologic response in locally advanced rectal cancer (LARC) treated with preoperative chemoradiation (CRT). Methods: The study included 50 patients with LARC treated with preoperative CRT. All patients were evaluated by PET-CT before and after CRT, and results were compared to histopathologic response quantified by tumour regression grade (patients with TRG 1-2 being defined as responders and patients with grade 3-5 as non-responders). Furthermore, the predictive value of metabolic imaging for pathologic complete response (ypCR) was investigated. Results: Responders and non-responders showed statistically significant differences according to Mandard's criteria for maximum standardized uptake value (SUVmax) before and after CRT with a specificity of 76,6% and a positive predictive value of 66,7%. Furthermore, SUVmax values after CRT were able to differentiate patients with ypCR with a sensitivity of 63% and a specificity of 74,4% (positive predictive value 41,2% and negative predictive value 87,9%); This rather low sensitivity and specificity determined that PET-CT was only able to distinguish 7 cases of ypCR from a total of 11 patients. Conclusions: We conclude that 18-F PET-CT performed five to seven weeks after the end of CRT can visualise functional tumour response in LARC. In contrast, metabolic imaging with 18-F PET-CT is not able to predict patients with ypCR accuratelyFounded by the Fundación Investigación Mutua Madrileña. We are indebted to M. Expósito Ruiz for statistical support. and to J-L Marín Aznar for pathologic analysisYe

Dihydrocapsiate does not increase energy expenditure nor fat oxidation during aerobic exercise in men with overweight/ obesity: a randomized, triple-blinded, placebo-controlled, crossover trial

Background: Prior evidence suggests that capsinoids ingestion may increase resting energy expenditure (EE) and fat oxidation (FATox), yet whether they can modulate those parameters during exercise conditions remains poorly understood. We hypothesized that dihydrocapsiate (DHC) ingestion would increase EE and specifically FATox during an acute bout of aerobic exercise at FATmax intensity (the intensity that elicits maximal fat oxidation during exercise [MFO]) in men with overweight/ obesity. Since FATmax and MFO during aerobic exercise appear to be indicators of metabolic flexibility, whether DHC has an impact on FATox in this type of population is of clinical interest. Methods: A total of 24 sedentary men (age = 40.2 ± 9.2 years-old; body mass index = 31.6 ± 4.5 kg/m2 [n = 11 overweight, n = 13 obese]) participated in this randomized, triple-blinded, placebocontrolled, crossover trial (registered under ClinicalTrials.gov Identifier no. NCT05156697). On the first day, participants underwent a submaximal exercise test on a cycle ergometer to determine their MFO and FATmax intensity during exercise. After 72 hours had elapsed, the participants returned on 2 further days (≥ 72 hours apart) and performed a 60 min steady-state exercise bout (i.e. cycling at their FATmax, constant intensity) after ingesting either 12 mg of DHC or placebo; these conditions were randomized. Respiratory gas exchange was monitored by indirect calorimetry. Serum marker concentrations (i.e. glucose, triglycerides, non-esterified fatty acids (NEFAs), skin temperature, thermal perception, heart rate, and perceived fatigue) were assessed. Results: There were no significant differences (P > 0.05) between DHC and placebo conditions in the EE and FATox during exercise. Similarly, no significant changes were observed in glucose, triglycerides, or NEFAs serum levels, neither in the skin temperature nor thermal perception across conditions. Heart rate and perceived fatigue did not differ between conditions. Conclusions: DHC supplementation does not affect energy metabolism during exercise in men with overweight/obesity.Spanish Junta de Andalucia via Consejeria de Conocimiento, Investigacion y Universidades, Proyectos I+D+i del Programa Operativo del Fondo Europeo de Desarrollo Regional (FEDER 2018) B.CTS.377.UGR18Spanish Government PTA 12264-I FPU16/02828 FPU16/0515

VDR gene polymorphisms on risk of osteoporotic hip fracture in an adult population spanish

La osteoporosis es una enfermedad esquelética compleja multifactorial con un fuerte componente genético, caracterizada por un deterioro en la microestructura ósea que causa fragilidad ósea y un incremento en el riesgo de fracturas osteoporóticas. El gen VDR podría estar fuertemente involucrado en el riesgo de fractura. El objetivo de este trabajo fue investigar la asociación entre polimorfismos del gen VDR y la susceptibilidad a fractura de cadera (FC). Se reclutaron 147 pacientes andaluces (102 con factores de riesgos de fracturas osteoporóticas y 45 con metabolismo óseo normal). El aislamiento de ADN se realizó a partir de 300 mL de sangre, genotipando 2 SNPs: BsmI y FokI mediante PCRRFLP (PCR-Restriction Fragment Length Polymorphism). Todas las fracturas fueron confirmadas por rayos-X mientras que el riesgo de fracturas a través de la escala FRAX y DMO. Los resultados se evaluaron estadísticamente, considerando significativo valores de p<0,05. La edad media de los pacientes fracturados fue de 68,5 años, cuyas frecuencias alélicas fueron 64.7% G y 68.6% C para BsmI y FokI, respectivamente. La prevalencia de estos SNPs en la población caso fueron: 43,3% GA, 43.3% GG y 13,7% AA para BsmI y 49,0% CC, 39,20% CT, 11,8% TT para FokI. Las frecuencias de los alelos y genotipos no mostraron diferencias entre pacientes con riesgo de fracturas y pacientes control. Las frecuencias están acorde con las demostradas en HapMap para población europeacaucásica. No se encontró ninguna asociación significativa entre estos SNPs y la susceptibilidad a las FC en la población adulta andaluza.Osteoporosis is a multifactorial complex skeletal disease with strong genetic component, characterized by a deterioration of bone microstructure that causes bone fragility and an increased risk of osteoporotic fractures. VDR gene could be strongly involved in the risk of fracture. The aim of this study was to investigate the association between VDR gene polymorphisms and susceptibility to hip fracture (HF). 147 Andalusian patients were recruited (102 with risk factors for osteoporotic fractures and 47 with normal bone metabolism). DNA isolation was performed from 300 mL of blood, genotyping 2 SNPs: BsmI and FokI by PCR-RFLP (PCR-Restriction Fragment Length Polymorphism). All fractures were confirmed by X-rays while the risk of fractures through FRAX level and BMD. The results were statistically evaluated, considering significant p-values <0.05. The average age of fractured patients was 68.5 years, whose allele frequencies were 64.7% G and 68.6% C for BsmI and FokI, respectively. Prevalence of these SNPs in the case population were: 43.3% GA, 43.3% GG and 13.7% AA BsmI and 49.0 % CC, 39.2% CT, 11.8% TT for FokI. The frequencies of alleles and genotypes showed no differences between patients with and without risk of hip fracture. The frequencies are agree to HapMap for European-Caucasian population. It was found no significant association between these SNPs and susceptibility to HF in the adult population of Andalusia

No evidence of brown adipose tissue activation after 24 weeks of supervised exercise training in young sedentary adults in the ACTIBATE randomized controlled trial

Exercise modulates both brown adipose tissue (BAT)metabolismand white adipose tissue (WAT) browning in murine models. Whether this is true in humans, however, has remained unknown. An unblinded randomized controlled trial (ClinicalTrials.gov ID: NCT02365129) was therefore conducted to study the effects of a 24-week supervised exercise intervention, combining endurance and resistance training, on BAT volume and activity (primary outcome). The study was carried out in the Sport and Health University Research Institute and the Virgen de las Nieves University Hospital of the University of Granada (Spain). One hundred and forty-five young sedentary adults were assigned to either (i) a control group (no exercise, n = 54), (ii) a moderate intensity exercise group (MOD-EX, n = 48), or (iii) a vigorous intensity exercise group (VIG-EX n = 43) by unrestricted randomization. No relevant adverse events were recorded. 97 participants (34 men, 63 women) were included in the final analysis (Control; n = 35, MOD-EX; n=31, and VIG-EX; n=31).We observed no changes in BAT volume (Δ Control: −22.2 ± 52.6ml; Δ MOD-EX: −15.5 ± 62.1ml, Δ VIG-EX: −6.8 ± 66.4 ml; P = 0.771) or 18F-fluorodeoxyglucose uptake (SUVpeak Δ Control: −2.6 ± 3.1ml; Δ MOD-EX: −1.2 ± 4.8, Δ VIG-EX: −2.2 ± 5.1; p = 0.476) in either the control or the exercise groups. Thus, we did not find any evidence of an exercise-induced change on BAT volume or activity in young sedentary adults.Spanish Government PI13/01393Retos de la Sociedad DEP2016-79512-R PTA-12264IEuropean CommissionSpanish Government FPU13/04365 FPU14/04172 FPU15/04059 FPU16/03653 FPU19/01609Consejo Nacional de Ciencia y Tecnologia (CONACyT) 440575Fundacion Iberoamericana de Nutricion (FINUT)Redes Tematicas de Investigacion Cooperativa RETIC Red SAMID RD16/0022AstraZenecaUniversity of Granada Plan Propio de Investigacion 2016 -Excellence actions: Unit of Excellence on Exercise and Health (UCEES)Plan Propio de Investigacion 2018 -Programa Contratos-PuentePrograma Perfecionamiento de DoctoresJunta de Andalucia Consejeria de Conocimiento, Investigacion y Universidades (ERDF) SOMM17/6107/UGRJunta de Andalucia P18-RT-4455Fundacion Alfonso Martin EscuderoMaria Zambrano fellowship by the Ministerio de Universidades y la Union Europea-NextGenerationEU RR_C_2021_04Novo Nordisk FoundationNovocure Limited NNF18OC003239

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline