Departamento de Fisiologíahttps://hdl.handle.net/10481/320462024-03-29T14:59:49Z2024-03-29T14:59:49ZThe emerging role of skeletal muscle mitochondrial dynamics in exercise and ageingRodríguez Huertas, Jesús Franciscohttps://hdl.handle.net/10481/888972024-02-09T13:29:46ZThe emerging role of skeletal muscle mitochondrial dynamics in exercise and ageing
Rodríguez Huertas, Jesús Francisco
Mitochondria are the hub for energy production within living cells. They can undergo morphological changes in
response to nutrient availability and cellular stress. Here, we review how exercise chronically and acutely affects
mitochondrial dynamics. Moreover, we discuss whether mitochondrial dysfunction observed in elderly subjects
is due to the ageing process per se or due to the associated sedentary state. Finally, we study how endurance
exercise can improve mitochondrial dynamics in older subjects, thereby improving their overall health and likely
limiting muscle waste.
Hydroxytyrosol influences exercise-induced mitochondrial respiratory complex assembly into supercomplexes in ratsCasuso, Rafael A.Al Fazazi, SaadHidalgo Gutiérrez, AgustínLópez García, Luis CarlosPlaza Díaz, JulioRueda Robles, AscensiónRodríguez Huertas, Jesús Franciscohttps://hdl.handle.net/10481/888942024-02-09T13:21:46ZHydroxytyrosol influences exercise-induced mitochondrial respiratory complex assembly into supercomplexes in rats
Casuso, Rafael A.; Al Fazazi, Saad; Hidalgo Gutiérrez, Agustín; López García, Luis Carlos; Plaza Díaz, Julio; Rueda Robles, Ascensión; Rodríguez Huertas, Jesús Francisco
Hydroxytyrosol (HT) has been demonstrated to improve mitochondrial function, both in sedentary and in exercised
animals. Herein, we assessed the effects of two different doses of HT on exercise-induced mitochondrial
respiratory complex (C) assembly into supercomplexes (SCs) and the relation of the potential results to OPA1
levels and oxidative stress. Wistar rats were allocated into six groups: sedentary (SED), sedentary consuming
20 mg/kg/d of HT (SED-20), sedentary consuming 300 mg/kg/d of HT (SED-300); exercised (EXE), exercised
consuming 20 mg/kg/d of HT (EXE-20) and exercised consuming 300 mg/kg/d of HT (EXE-300). Animals were
exercised and/or supplemented for 10 weeks, and assembly of SCs, mitochondrial oxidative status and expression
of OPA1 were quantified in the gastrocnemius muscle. Both EXE and EXE-20 animals exhibited increased
assembly of CI into SCs, but this effect was absent in EXE-300 animals. Levels of CIII2 assembled into SCs
were only increased in EXE-20 animals. Notably EXE-300 animals showed a decreased relative expression of s-
OPA1 isoforms. Therefore, HT exerted dose-dependent effects on SC assembly in exercised animals. Although the
mechanisms leading to SCs assembly in response to exercise and HT are unclear, it seems that a high HT dose can
prevent SCs assembly during exercise by decreasing the expression of the s-OPA1 isoforms.
Human muscular mitochondrial fusion in athletes during exerciseRodríguez Huertas, Jesús Franciscohttps://hdl.handle.net/10481/888832024-02-09T12:59:24ZHuman muscular mitochondrial fusion in athletes during exercise
Rodríguez Huertas, Jesús Francisco
ABSTRACT: The main objective of this work was to investigate whether mitochondrial fusion occurs in the skeletal
muscle of well-trained athletes in response to high-intensity exercise. Well-trained swimmers (n = 9) performed a
duration-matched sprint interval training (SIT) and high-intensity high-volume training (HIHVT) session on separate
days. Muscle samples from triceps brachii were taken before, immediately after, and 3 h after the training
sessions. Transmission electron microscopy (TEM) was applied to assess mitochondrial morphology. Moreover,
expression of genes coding for regulators of mitochondrial fusion and fission were assessed by real-time quantitative
PCR. In addition, mitofusin (MFN)2 and optic atrophy 1 (OPA1) were quantified by Western blot analysis.
TEManalyses showed thatmitochondrialmorphology remained altered for 3 h afterHIHVT,whereas SIT-induced
changes were only evident immediately after exercise. Only SIT increased MFN1 and MFN2 mRNA expression,
whereas SIT and HIHVT both increasedMFN2 protein content 3 h after exercise. Notably, only HIHVT increased
OPA1 protein content. Mitochondrial morphologic changes that suggest fusion occurs in well-adapted athletes
during exercise. However, HIHVT appears as a more robust inducer of mitochondrial fusion events than SIT.
Indeed, SIT induces a rapid and transient change in mitochondrialmorphology.—Huertas, J. R., Ruiz-Ojeda, F. J.,
Plaza-D´ıaz, J., Nordsborg, N. B.,Mart´ın-Albo, J., Rueda-Robles, A., Casuso, R. A. Human muscular mitochondrial
fusion in athletes during exercise. FASEB J. 33, 12087–12098 (2019). www.fasebj.org
Hydroxytyrosol modifies skeletal muscle GLUT4/AKT/Rac1 axis in trained ratsRodríguez Huertas, Jesús Franciscohttps://hdl.handle.net/10481/888822024-02-09T12:58:13ZHydroxytyrosol modifies skeletal muscle GLUT4/AKT/Rac1 axis in trained rats
Rodríguez Huertas, Jesús Francisco
Training induces a number of healthy effects including a rise in skeletal muscle (SKM)
glucose uptake. These adaptations are at least in part due to the reactive oxygen
species produced within SKM, which is in agreement with the notion that antioxidant
supplementation blunts some training‐induced adaptations. Here, we tested whether
hydroxytyrosol (HT), the main polyphenol of olive oil, would modify the molecular
regulators of glucose uptake when HT is supplemented during exercise. Rats were
included into sedentary and exercised (EXE) groups. EXE group was further divided
into a group consuming a low HT dose (0.31 mg·kg·d; EXElow), a moderate HT dose
(4.61mg·kg·d; EXEmid), and a control group (EXE). EXE raised glucose transporter
type 4 (GLUT4) protein content, Ras‐related C3 botulinum toxin substrate 1 (Rac1)
activity, and protein kinase b (AKT) phosphorylation in SKM. Furthermore, EXElow
blunted GLUT4 protein content and AKT phosphorylation while EXEmid showed a
downregulation of the GLUT4/AKT/Rac1 axis. Hence, a low‐to‐moderate dose of HT,
when it is supplemented as an isolated compound, might alter the beneficial effect of
training on basal AKT phosphorylation and Rac1 activity in rats.
Mitochondrial adaptations to calorie restriction and bariatric surgery in human skeletal muscle: a systematic review with meta-analysisRodríguez Huertas, Jesús Franciscohttps://hdl.handle.net/10481/888802024-02-09T12:56:04ZMitochondrial adaptations to calorie restriction and bariatric surgery in human skeletal muscle: a systematic review with meta-analysis
Rodríguez Huertas, Jesús Francisco
Objective: We performed a meta-analysis to determine the changes induced by calorie restriction (CR) and bariatric
surgery on human skeletal muscle mitochondria.
Methods: A systematic search of Medline and Web of Science was conducted. Controlled trials exploring CR (≥14
days) and mitochondrial function and/or content assessment were included. Moreover, studies analyzing weight
loss following gastric surgery were included for comparison purposes. Human muscle data from 28 studies
assessing CR (520 muscle samples) and from 10 studies assessing bariatric surgery (155 muscle samples) were
analyzed in a random effect meta-analysis with three a priori chosen covariates.
Main results: We report a decrease (p < 0.05) (mean (95 % CI)) in maximal mitochondrial state 3 respiration in
response to CR (����� 0.44 (����� 0.85, ����� 0.03)) but not in response to surgery (����� 0.33 (����� 1.18, 0.52)). No changes in
mitochondrial content were reported after CR (����� 0.05 (����� 0.12, 0.13)) or in response to surgery (0.23 (����� 0.05,
0.52)). Moreover, data from CR subjects showed a reduction in complex IV (CIV) activity (����� 0.29 (����� 0.56, ����� 0.03))
but not in CIV content (����� 0.21 (����� 0.63, 0.22)). Similar results were obtained when the length of the protocol, the
initial body mass index, and the estimated energy deficit were included in the model as covariates.
Conclusion: The observation of reduced maximal mitochondrial state 3, uncoupled respiration, and CIV activity
without altering mitochondrial content suggests that, in human skeletal muscle, CR mainly modulates intrinsic
mitochondrial function.