BUSCADOR RECOLECTA

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 efcient 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-fuorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography scan (PET/CT) after a
2 h personalized cooling protocol. 18F-FDG uptake was also quantifed 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
Bifdobacterium 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 Bifdobacteriaceae 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 confrm these fndings.
Clinical trial information ClinicalTrials.gov no. NCT02365129 (registered 18 February 2015)., Funding for open access charge: Universidad de Granada / CBUA. The study was supported by the Spanish Ministry of Economy and Competitiveness via Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (PI13/01393) and PTA 12264-I, Retos de la Sociedad (DEP2016- 79512-R), and European Regional Development Funds (ERDF), by the Spanish Ministry of Education (FPU13/04365, FPU16/05159 and FPU17/01523), the Fundación Iberoamericana de Nutrición (FINUT), the Redes Temáticas De Investigación Cooperativa RETIC (Red SAMID RD16/0022), InFLAMES Flagship Programme of the Academy of Finland (decision number: 337530), Fundación Alfonso Martin Escudero and NextGenerationEU (Maria Zambrano fellowship: RR_C_2021_04). AstraZeneca HealthCare Foundation, the University of Granada Plan Propio de Investigación 2016-Excellence actions: Unit of Excellence on Exercise and Health (UCEES), and by the Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades (ERDF, SOMM17/6107/UGR). AL and RVV are supported by the funds of the European Commission through the “European funds for regional development” (EFRE) as well as by the regional Ministry of Economy, Science and Digitalization of Saxony-Anhalt as part of the “Autonomy in old Age” (AiA) research group for “LiLife” Project (Project ID: ZS/2018/11/95324). We would like to thank the team of the Data Integration Center of University Medicine Magdeburg for local data-analysis solutions; they are supported by MIRACUM and funded by the German Federal Ministry of Education and Research (BMBF) within the “Medical Informatics Funding Scheme” (FKZ 01ZZ1801H).

Exercise modulates both brown adipose tissue (BAT) metabolism and 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 ± 52.6 ml; Δ MOD-EX:
−15.5 ± 62.1 ml, Δ VIG-EX: −6.8 ± 66.4 ml; P = 0.771) or 18F-fluorodeoxyglucose
uptake (SUVpeak Δ Control: −2.6 ± 3.1 ml; 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., This study was funded by the Spanish Ministry of Economy and Competitiveness via the Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (PI13/01393; J.R.R.) and PTA-12264I, Retos de la Sociedad (DEP2016-79512-R; J.R.R.) and European Regional Development Funds (ERDF; J.R.R.), the Spanish Ministry of Education (FPU13/04365 (G.S.D.), FPU14/04172 (F.A.G.), FPU15/04059 (J.M.A.), FPU16/03653 (A.M.G.), FPU16/02828 (F.J.O.P.), FPU16/05159 (H.X.), FPU17/01523 (L.O.A.), FPU19/01609 (L.J.F.)), International Doctoral Studies Scholarship no. 440575 from the Mexican National Council of Science and Technology (CONACYT; WDMA), the Fundación Iberoamericana de Nutrición (FINUT; JRR), the Redes Temáticas de Investigación Cooperativa RETIC (Red SAMID RD16/0022; J.R.R.), the AstraZeneca HealthCare Foundation (J.R.R.), the University of Granada Plan Propio de Investigación 2016 -Excellence actions: Unit of Excellence on Exercise and Health (UCEES) (J.R.R.)- and Plan Propio de Investigación 2018 - Programa Contratos-Puente and Programa Perfecionamiento de Doctores (G.S.D.), the Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades (ERDF; ref. SOMM17/6107/UGR; JRR), the Junta de Andalucía, Consejería de Economía, Conocimiento, Empresas y Universidad (ref. P18-RT-4455; J.R.R.), the Fundación Alfonso Martín Escudero (B.M.T. and G.S.D.), the Maria Zambrano fellowship by the Ministerio de Universidades y la Unión Europea NextGenerationEU (RR_C_2021_04; B.M.T.), and the Novo Nordisk Foundation (NNF18OC0032394; M.S.).

Currently, the elderly population is expanding due to an unprecedented increase in longevity. Unfortunately, this trend in the rising ageing population comes with the consequences of the augmentation of physiological decline leading to metabolic diseases or oxidative stress. Oxidative stress has been defined as a pathophysiological state characterised by an imbalance between the excessive production of oxidants (such as homocysteine, HCY) and the inability of the total antioxidant capacity (TAC) of the body to cope with them. When this condition occurs an accumulation of oxidatively damaged macromolecules appears, leading to the loss of function of these macromolecules which contributes to the appearance of no communicable diseases such as cardiovascular diseases or musculoskeletal diseases.

Consequently, it is needed to know how different factors can help to maintain healthy ageing in older adults. Maintaining good physical fitness, adequate levels of physical activity (PA), and healthy sleep behaviour have been shown to reduce the possible mechanisms of ageing such as oxidative stress. However, to our knowledge, it is still unknown whether these factors can differently affect the oxidative stress of older adults depending on sex since most of the studies analysed the data combined.

Therefore, the general aim of this International Doctoral Thesis was to study the sex-specific associations of anthropometry, body composition, physical fitness, PA, sedentarism and sleep behaviour with oxidative stress levels, in a sample of Spanish older adults.

This International Doctoral Thesis includes cross-sectional data from the INTERMAE project. A total of 76 participants (38 women, 68.8 ± 3.0 years old) recruited through the public health care centers of the province of Cádiz were included. Blood samples were obtained from the participants to obtain the plasma levels of TAC and serum levels of HCY. Then participants completed different measurements including body composition, physical fitness through different physical batteries and cardiorespiratory fitness test (CRF), nutritional evaluation, and questionnaires about their PA and sleep manners. In addition to this, participants wore an accelerometer for at least 7 days to estimate their sedentary (SB), PA and sleep behaviours.

The main findings of this International Doctoral Thesis are i) there are sex differences in basal oxidative stress markers in Spanish older adults, regardless of their nutritional intake., ii) Higher body mass index and thigh perimeter in women and higher fat-free mass in men are associated with higher levels of HCY. iii) In older women a faster gait speed is associated with higher levels of TAC. Better upper body strength, flexibility and gait agility are associated with lower levels of HCY. Higher CRF is associated with lower levels of HCY in both sexes. (Study 1); iv) PA levels seem to be more relevant to older adults? oxidative stress than SB, with moderate to vigorous PA being associated with increasing TAC and light PA with decreasing HCY in both sexes (Study 2); v) Sleep disorders were associated with oxidative stress in older adults, with more time awake during the night associated with a decreased TAC in women and a higher sleep latency being associated with higher levels of HCY in men (Study 3).

The findings of the present International Doctoral Thesis show that there are sex-specific associations of anthropometric, body composition, physical fitness, PA and sleep behaviour with oxidative stress in older adults., En la actualidad se está produciendo un aumento en el número de personas mayores
debido a un incremento de la longevidad sin precedentes. Por desgracia esta
tendencia de envejecimiento viene acompañado de un aumento del deterioro
fisiológico derivando en enfermedades metabólicas o estrés oxidativo. El estrés
oxidativo se ha definido como un estado pato fisiológico caracterizado por un
desequilibrio entre la excesiva producción de oxidantes (como la homocisteína,
HCY) sumada a una incapacidad de la capacidad antioxidante total (TAC) de hacerle
frente. Cuando esta condición ocurre, se produce una acumulación de
macromoléculas con daño oxidativo que contribuyen a la aparición de
enfermedades no comunicables como enfermedades cardiovasculares o músculoesqueléticas.
Por lo tanto, es necesario conocer como diferentes factores pueden ayudar a
mantener un envejecimiento saludable en nuestra población. Mantener un buen
estado físico, niveles adecuados de actividad física (PA) y unos hábitos de sueño
saludable se han determinado como factores protectores ante mecanismos que
pueden afectar al envejecimiento como el estrés oxidativo. Sin embargo, bajo
nuestro conocimiento, se desconoce si estos factores pueden afectar de forma
diferente al estrés oxidativo de las personas mayores dependiendo del sexo debido
a que la mayoría de los estudios analizan ambos sexos de forma combinada.
Por lo tanto, el objetivo general de esta Tesis Doctoral Internacional fue el de evaluar
las asociaciones de diferentes componentes de antropometría, composición
corporal, estado físico, actividad física, sedentarismo y hábitos de sueño sobre el
estrés oxidativo en una muestra de adultos mayores españoles y si estas
asociaciones tenían diferencias dependiendo del sexo.
Esta Tesis Doctoral Internacional incluye datos transversales del proyecto
INTERMAE. Un total de 76 participantes (38 mujeres, 68.8 ± 3.0 años) que fueron
reclutados a través centros de salud pública de la provincia de Cádiz fueron
incluidos. Se obtuvieron muestras de sangre para analizar la TAC del plasma y los
niveles de HCY del suero. Adicionalmente, los participantes completaron diferentes
mediciones incluyendo antropometría, composición corporal, estado físico a través de diferentes baterías y un test de fitness cardiorrespiratorio (CRF), evaluación
nutricional, y cuestionarios sobre sus hábitos de actividad física y sueño. Asimismo,
los participantes llevaron un acelerómetro durante 7 días para estimar su
comportamiento sedentario (SB), de actividad física (PA) y de sueño.
Los principales hallazgos de esta Tesis Doctoral Internacional fueron: i) Existen
diferencias sexuales en los niveles basales de estrés oxidativo en nuestros adultos
mayores españoles, sin importar su ingesta nutricional. ii) El Índice de Masa
Corporal y el perímetro de muslo en mujeres y los niveles de masa libre de grasa en
hombres se asocian con niveles incrementados de HCY. En mujeres mayores una
velocidad de la marcha alta se asocia con niveles más altos de TAC. Una mayor fuerza
y flexibilidad del tren superior, así como una mejor agilidad de la marcha se asocian
con menores niveles de HCY en mujeres. Niveles más altos de CRF se asocian con
niveles más bajos de HCY en ambos sexos (Estudio 1), iii) Los niveles de PA parecen
ser más relevantes para el estrés oxidativo de las personas mayores que el SB, con
la PA de moderada a vigorosa estando asociada con una TAC incrementada y los
niveles de PA ligera estando asociados con niveles reducidos de HCY (Estudio 2). iv)
Los trastornos del sueño se asociaron con el estrés oxidativo de las personas
mayores, con un tiempo despierto durante la noche mayor estando asociado con una
menor TAC en mujeres y una mayor latencia de sueño estando asociado con mayores
niveles de HCY en hombres (Estudio 3).
Los hallazgos de la presente Tesis Doctoral Internacional muestran que existen
asociaciones específicas para cada sexo entre variables antropométricas, de
composición corporal, de estado físico, actividad física y hábitos de sueño en
personas mayores.

Where people live and work together it is not always possible to modify the ambient temperature; ways must therefore be found that allow individuals to feel thermally comfortable in such settings. The Embr Wave (R) is a wrist-worn device marketed as a 'personal thermostat' that can apply a local cooling stimulus to the skin. The aim of the present study was to determine the effect of an intermittent mild cold stimulus of 25 degrees C for 15-20 s every 5 min over 3.5 days under free-living conditions on 1) skin temperature, 2) perception of skin temperature, 3) sleep quality and 4) resting energy expenditure (REE) in young, healthy adults. Ten subjects wore the device for 3.5 consecutive days. This intervention reduced distal skin temperature after correcting for personal ambient temperature (P < 0.05), but did not affect the subjects' the perception of skin temperature, sleep quality or REE (all P >= 0.051). Thus, this intermittent mild cold regime can reduce distal skin temperature, and wearing it under free-living conditions for 3.5 days does not seem to impair the perception of skin temperature and sleep quality or modify REE., The study was funded by the Spanish Ministry of Economy and Competitiveness via the Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III (PI13/01393 and CB16/10/00239) and PTA 12264-I, Retos de la Sociedad (DEP2016-79512-R), and European Regional Development Funds (ERDF). Other funders included the Spanish Ministry of Education (FPU 16/05159, 15/04059 and 19/02326), the Fundacion Iberoamericana de Nutricion (FINUT), the Redes Tematicas De Investigacion Cooperativa RETIC (Red SAMID RD16/0022), the AstraZeneca Health Care Foundation, the University of Granada Plan Propio de Investigacion 2016 (Excellence actions: Unit of Excellence on Exercise, Nutrition and Health [UCEENS]), and by the Junta de Andalucia, Consejeria de Conocimiento, Investigacion y Universidades (ERDF, SOMM17/6107/UGR). AMT was supported by Seneca Foundation through grant 19899/GERM/15 and the Ministry of Science Innovation and Universities RTI2018-093528-B-I0, as well as DJP (MINECO; RYC-2014-16938). BMT was supported by an individual postdoctoral grant from the Fundacion Alfonso Martin Escudero. We thank Dr. Matt Smith of Embr Labs Inc. for configuring the Embr Wave (R) devices used in this experiment.