The effect of Mitoquinol (MitoQ) on heat stressed skeletal muscle from pigs, and a potential confounding effect of biological sex

Rudolph, Tori; Mayorga, E.J.; Roths, Melissa; Rhoads, Robert P.; Baumgard, Lance H.; Selsby, Joshua T.

doi:10.1016/j.jtherbio.2021.102900

Cited by 11 publications

(5 citation statements)

References 42 publications

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“…Notably, the previous studies employed different species and a dissimilar dose regimen (~4 mg/kg) than that utilized herein, which may explain the discrepancies in MitoQ effects across studies. Surprisingly, we did not detect an oxidative stress response in skeletal muscle in these exact pigs ( Rudolph et al, 2021 ), and we did not measure oxidative stress in the intestinal tissues or circulation. Thus, it is possible that oxidative stress did not occur in our model using barrows, a scenario that would have limited our ability to test the antioxidative effects of MitoQ; though may rise questions about the potential role of biological sex on HS-mediated outcomes.…”

Section: Discussionmentioning

confidence: 75%

“…All experimental procedures followed the guidelines for the ethical and humane use of animals for research according to the Guide for the Care and Use of Agricultural Animals in Research and Teaching ( FASS, 2010 ) and were approved by the Iowa State University Institutional Animal Care and Use Committee (#18-314). Data about HS-mediated changes in skeletal muscle from these pigs have been previously reported ( Rudolph et al, 2021 ).…”

Section: Methodsmentioning

confidence: 95%

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Therapeutic effects of mitoquinol during an acute heat stress challenge in growing barrows

Mayorga,

Horst,

Goetz

et al. 2024

Journal of Animal Science

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Study objectives were to determine the effects of mitoquinol (MitoQ, a mitochondrial-targeted antioxidant) on biomarkers of metabolism and inflammation during acute heat stress (HS). Crossbred barrows [n = 32; 59.0 ± 5.6 kg body weight (BW)] were blocked by BW and randomly assigned to 1 of 4 environmental-therapeutic treatments: 1) thermoneutral (TN) control (n = 8; TNCon), 2) TN and MitoQ (n = 8; TNMitoQ), 3) HS control (n = 8; HSCon), or 4) HS and MitoQ (n = 8; HSMitoQ). Pigs were acclimated for 6 d to individual pens before study initiation. The trial consisted of two experimental periods (P). During P1 (2 d), pigs were fed ad libitum and housed in TN conditions (20.6 ± 0.8 °C). During P2 (24 h), HSCon and HSMitoQ pigs were exposed to continuous HS (35.2 ± 0.2 °C), while TNCon and TNMitoQ remained in TN conditions. MitoQ (40 mg/d) was orally administered twice daily (0700 and 1800 hours) during P1 and P2. Pigs exposed to HS had increased rectal temperature, skin temperature, and respiration rate (+1.5 °C, +6.8 °C, and +101 breaths per minute, respectively; P < 0.01) compared to their TN counterparts. Acute HS markedly decreased feed intake (FI; 67%; P < 0.01); however, FI tended to be increased in HSMitoQ relative to HSCon pigs (1.5 kg vs. 0.9 kg, respectively; P = 0.08). Heat-stressed pigs lost BW compared to their TN counterparts (−4.7 kg vs. +1.6 kg, respectively; P < 0.01); however, the reduction in BW was attenuated in HSMitoQ compared to HSCon pigs (−3.9 kg vs. −5.5 kg, respectively; P < 0.01). Total gastrointestinal tract weight (empty tissue and luminal contents) was decreased in HS pigs relative to their TN counterparts (6.2 kg vs. 8.6 kg, respectively; P < 0.01). Blood glucose increased in HSMitoQ relative to HSCon pigs (15%; P = 0.04). Circulating non-esterified fatty acids (NEFA) increased in HS compared to TN pigs (P < 0.01), although this difference was disproportionately influenced by elevated NEFA in HSCon relative to HSMitoQ pigs (251 μEq/L vs. 142 μEq/L; P < 0.01). Heat-stressed pigs had decreased circulating insulin relative to their TN counterparts (47%; P = 0.04); however, the insulin:FI ratio tended to increase in HS relative to TN pigs (P = 0.09). Overall, circulating leukocytes were similar across treatments (P > 0.10). Plasma C-reactive protein remained similar among treatments; however, haptoglobin increased in HS relative to TN pigs (48%; P = 0.03). In conclusion, acute HS exposure negatively altered animal performance, inflammation, and metabolism, which were partially ameliorated by MitoQ.

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Section: Discussionmentioning

confidence: 75%

Section: Methodsmentioning

confidence: 95%

Therapeutic effects of mitoquinol during an acute heat stress challenge in growing barrows

Mayorga,

Horst,

Goetz

et al. 2024

Journal of Animal Science

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“…pigs [30]. Thus, the absence of gene expression changes in male muscles at mid-gestation might be due to their earlier adaptation to maternal HS, as a consequence of rapid muscle growth, hence the lack of differences at the time of sampling on d 60.…”

Section: Discussionmentioning

confidence: 99%

Gestational heat stress alters skeletal muscle gene expression profiles and vascularity in fetal pigs in a sexually dimorphic manner

Zhao

Green

Marth

et al. 2022

J Animal Sci Biotechnol

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Background There is evidence that sow heat stress (HS) during gestation affects fetal development with implications for impaired muscle growth. We have previously demonstrated that maternal HS during early to mid-gestation compromised muscle fibre hyperplasia in developing fetal pigs. Thus, we hypothesised these phenotypic changes are associated with a change in expression of genes regulating fetal skeletal muscle development and metabolism. To test this, at d 60 of gestation, RNA sequencing and immunohistochemistry were performed on fetal longissimus dorsi (LD) muscle biopsies collected from pregnant gilts that had experienced either thermoneutral control (CON, 20 °C, n = 7 gilts, 18 LD samples) or controlled HS (cyclic 28 to 33 °C, n = 8 gilts, 23 LD samples) conditions for 3 weeks. Results A total of 282 genes were differentially expressed between the HS and CON groups in female LD muscles (false discovery rate (FDR) ≤ 0.05), whereas no differentially expressed genes were detected in male LD muscles between the two groups (FDR > 0.05). Gestational HS increased the expression of genes associated with transcription corepressor activity, adipogenesis cascades, negative regulation of angiogenesis and pro-inflammatory signalling in female LD muscles. Immunohistochemical analyses revealed a decreased muscle vascularity density in fetuses from HS group for both sexes compared to those from the CON group (P = 0.004). Conclusions These results reveal gilt HS during early to mid-gestation altered gene expression profiles in fetal LD muscles in a sexually dimorphic manner. The molecular responses, including transcription and angiogenesis repressions and enhanced adipogenesis cascades, were exclusively observed in females. However, the associated reductions in muscle vascularity were observed independently of sexes. Collectively this may indicate female fetal pigs are more adaptive to gestational HS in terms of gene expression changes, and/or there may be sexually dimorphic differences with respect to the timing of muscle molecular responses to gestational HS.

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“…Furthermore, heat stress can increase SIRT1 protein expression, which may augment PGC-1α activity and thus, mitochondrial content [ 18 ]. Heat is also likely to increase oxidative stress in skeletal muscle, which has been well studied in avian and porcine models [ 45 , 46 , 47 , 48 ]. Therefore, it is possible that short-wave diathermy leads to mild increases in oxidative stress, resulting in signaling for mitochondrial adaptation.…”

Section: Discussionmentioning

confidence: 99%

Localized Heat Therapy Improves Mitochondrial Respiratory Capacity but Not Fatty Acid Oxidation

Marchant

Kaluhiokalani²,

Wallace³

et al. 2022

IJMS

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AIM: Mild heat stress can improve mitochondrial respiratory capacity in skeletal muscle. However, long-term heat interventions are scarce, and the effects of heat therapy need to be understood in the context of the adaptations which follow the more complex combination of stimuli from exercise training. The purpose of this work was to compare the effects of 6 weeks of localized heat therapy on human skeletal muscle mitochondria to single-leg interval training. METHODS: Thirty-five subjects were assigned to receive sham therapy, short-wave diathermy heat therapy, or single-leg interval exercise training, localized to the quadriceps muscles of the right leg. All interventions took place 3 times per week. Muscle biopsies were performed at baseline, and after 3 and 6 weeks of intervention. Mitochondrial respiratory capacity was assessed on permeabilized muscle fibers via high-resolution respirometry. RESULTS: The primary finding of this work was that heat therapy and exercise training significantly improved mitochondrial respiratory capacity by 24.8 ± 6.2% and 27.9 ± 8.7%, respectively (p < 0.05). Fatty acid oxidation and citrate synthase activity were also increased following exercise training by 29.5 ± 6.8% and 19.0 ± 7.4%, respectively (p < 0.05). However, contrary to our hypothesis, heat therapy did not increase fatty acid oxidation or citrate synthase activity. CONCLUSION: Six weeks of muscle-localized heat therapy significantly improves mitochondrial respiratory capacity, comparable to exercise training. However, unlike exercise, heat does not improve fatty acid oxidation capacity.

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The effect of Mitoquinol (MitoQ) on heat stressed skeletal muscle from pigs, and a potential confounding effect of biological sex

Cited by 11 publications

References 42 publications

Therapeutic effects of mitoquinol during an acute heat stress challenge in growing barrows

Therapeutic effects of mitoquinol during an acute heat stress challenge in growing barrows

Gestational heat stress alters skeletal muscle gene expression profiles and vascularity in fetal pigs in a sexually dimorphic manner

Localized Heat Therapy Improves Mitochondrial Respiratory Capacity but Not Fatty Acid Oxidation

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