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exercise during weight loss improves hepatic mitophagy

Sports Medicine and Health Science 2022年第3期4卷 183-189页

作者： megan e.rosa-caldwell Kaylee e.Poole Andrew Seija Matthew P.Harris Nicholas P.Greene Joshua S.Wooten Cacheixia Research Laboratory Exercise Science Research CenterDepartment of HealthHuman Performanceand RecreationUniversity of ArkansasFayettevilleARUSA Department of Neurology Beth Israel Deaconess Medical CenterBostonMAUSA Department of Applied Health Southern Illinois University EdwardsvilleEdwardsvilleILUSA

Non-alcoholic fatty liver disease(NAFLD)has recently become a public health concern concurrent with the obesity crisis.Previous work has shown aberrant mitochondrial content/quality and autophagy in models of NAFLD,whereas exercise is known to improve these derangements.The purpose of this study was to examine the effect of different weight-loss modalities on hepatic mitochondrial content,autophagy and mitophagy in NAFLD.Forty-eight male C57BL/6J mice were divided into 1 of 4 groups:low fat diet(LFD,10%fat,18 weeks),high fat diet(HFD,60%fat diet,18 weeks),weight-loss by diet(D,60%fat diet for 10 weeks then 10%fat diet for 8 weeks)or weight-loss by diet and physical activity(D/PA,60%fat diet for 10 weeks,then 10%fat diet plus a running wheel for 8 weeks).Immunoblot data were analyzed by one-way analysis of variance(ANOVA)with significance denoted at pein contents were approximately 50%less in HFD compared to LFD.D/PA had 50%more BNIP3 compared to HFD.PINK1 content was 40%higher in D and D/PA compared to LFD.PPARKIN/PARKIN levels were 40%lower in HFD,D,and D/PA compared to LFD.Whereas p-UbSer65 was 3-fold higher in HFD.LC3II/I ratio was 50%greater in HFD and D/PA,yet p62 protein content was 2.5 fold higher in HFD.High-fat diet causes disruptions in markers of mitochondrial quality control.Physical activity combined with diet were able to ameliorate these derangements and seemingly improve hepatic mitochondrial quality above control values.

关键词： Autophagy High-fat diet Mitochondria Hepatic metabolism

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Sex differences in muscle health in simulated micro-and partial-gravity environments in rats

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Sports Medicine and Health Science 2023年第4期5卷 319-328页

作者： megan e.rosa-caldwell Marie Mortreux Anna Wadhwa Ursula B.Kaiser Dong-Min Sung Mary L.Bouxsein Seward B.Rutkove Department of Neurology Beth Israel Deaconess Medical Center and Harvard Medical School330 Brookline AvenueBostonMA02215USA Department of Nutrition and Food Sciences University of Rhode IslandKingstonRI02881USA Division of endocrinology Diabetes and HypertensionBrigham and Womenʼs Hospital and Harvard Medical SchoolBostonMA02215USA Center for Advanced Orthopedic Studies Beth Israel Deaconess Medical Center and Harvard Medical SchoolBostonMA02215USA

Skeletal muscle size and strength are important for overall health for astronauts.However,how male and female muscle may respond differently to micro-and partial-gravity environments is not fully understood.The purpose of this study was to determine how biological sex and sex steroid hormones influence the progression of muscle atrophy after long term exposure to micro and partial gravity environments in male and female rats.Male and female Fisher rats(n=120)underwent either castration/ovariectomy or sham surgeries.After two weeks recovery,animals were divided into microgravity(0g),partial-gravity(40%of weight bearing,0.4g),or full weight bearing(1g)interventions for 28 days.Measurements of muscle size and strength were evaluated prior to and after interventions.At 0g,females lost more dorsiflexion strength,plantar flexion strength,and other metrics of muscle size compared to males;castration/ovariectomy did not influence these differences.Additionally,at 0.4g,females lost more dorsiflexion strength,plantar flexion strength,and other metrics of muscle strength compared to males;castration/ovariectomy did not influence these differences.Females have greater musculoskeletal aberrations during exposure to both microgravity and partial-gravity environments;these differences are not dependent on the presence of sex steroid hormones.Correspondingly,additional interventions may be necessary to mitigate musculoskeletal loss in female astronauts to protect occupational and overall health.

关键词： Sex differences Atrophy Muscle strength Plantar flexion Dorsiflexion

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effects of PGC-1αoverexpression on the myogenic response during skeletal muscle regeneration

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Sports Medicine and Health Science 2022年第3期4卷 198-208页

作者： Tyrone A.Washington Wesley S.Haynie eleanor R.Schrems Richard A.Perry Jr. Lemuel A.Brown Breanna M.Williams megan e.rosa-caldwell David e.Lee Jacob L.Brown exercise Muscle Biology Laboratory Exercise Science Research CenterDepartment of HealthHuman Performance and RecreationUniversity of ArkansasFayettevilleAR72701USA Cachexia Research Laboratory Exercise Science Research CenterDepartment of HealthHuman Performance and RecreationUniversity of ArkansasFayettevilleAR72701USA

The ability of skeletal muscle to regenerate from injury is crucial for locomotion,metabolic health,and quality of life.Peroxisome proliferator-activated receptor-γcoactivator-1α(PGC1A)is a transcriptional coactivator required for mitochondrial biogenesis.Increased mitochondrial biogenesis is associated with improved muscle cell differentiation,however PGC1A's role in skeletal muscle regeneration following damage requires further investigation.The purpose of this study was to investigate the role of skeletal muscle-specific PGC1A overexpression during regeneration following damage.22 C57BL/6J(WT)and 26 PGC1A muscle transgenic(A1)mice were injected with either phosphate-buffered saline(PBS,uninjured control)or Bupivacaine(MAR,injured)into their tibialis anterior(TA)muscle to induce skeletal muscle damage.TA muscles were extracted 3-or 28-days postinjury and analyzed for markers of regenerative myogenesis and protein turnover.Pgc1a mRNA was~10–20 fold greater in A1 mice.Markers of protein synthesis,AKT and 4eBP1,displayed decreases in A1 mice compared to WT at both timepoints indicating a decreased protein synthetic response.Myod mRNA was~75%lower compared to WT 3 days post-injection.WT mice exhibited decreased cross-sectional area of the TA muscle at 28 days post-injection with bupivacaine compared to all other groups.PGC1A overexpression modifies the myogenic response during regeneration.

关键词： PGC-1α Skeletal muscle Muscle regeneration Satellite cells Protein turnover p38 MAPK

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Mapping super-resolution image quality

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Light(Science & Applications) 2024年第2期13卷 178-180页

作者： megan A.Steves Ke Xu Department of Chemistry University of CaliforniaBerkeleyCA94720USA

The local quality of super-resolution microscopy images can be assessed and mapped by rolling Fourier ring correlation,even when image quality varies within a single image.

关键词： image resolution Mapping

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Recent advances and future therapy development for Alzheimer’s disease and related disorders

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Neural Regeneration Research 2024年第9期19卷 1877-1878页

作者： megan Hong Gal Bitan Department of Neurology David Geffen School of MedicineUniversity of California Los AngelesLos AngelesCAUSA Department of Chemistry and Biochemistry University of California Los AngelesLos AngelesCAUSA Molecular Biology Institute University of California Los AngelesLos AngelesCAUSA Brain Research Institute University of CaliforniaLos AngelesCAUSA

Over 55 million people globally live with Alzheimer’s disease(AD)or related dementias(ADRD)and the number is expected to double every twenty years.Unt i l recent l y,onl y symptomatic treatments were available to patients with AD,including acetylcholine esterase inhibitors,of which the last one,galantamine,was approved by the US Food and Drug Administration(FDA)in 2001.

关键词： Alzheimer globally patients

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Neither autophagy nor exercise training mode affect exercise-induced beneficial adaptations in high fat-fed mice

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Sports Medicine and Health Science 2020年第1期2卷 44-53页

作者： megan e.rosa-caldwell Lisa T.Jansen Seongkyun Lim Kirsten R.Dunlap Wesley S.Haynie Tyrone A.Washington Nicholas P.Greene Integrative Muscle Metabolism Laboratory Exercise Science Research CenterDepartment of Human Health Performance and RecreationUniversity of ArkansasUSA exercise Muscle Biology Laboratory Exercise Science Research CenterDepartment of Human Health Performance and RecreationUniversity of ArkansasUSA

exercise mitigates obesity-associated pathologies;however,there is controversy regarding optimal exercise interventions.Autophagy,is known to decrease during obesity and is an important moderator for exercise adaptations.Purpose:To investigate individual and combined effects of different exercise interventions and autophagy inhibition on exercise adaptations during obesity.Methods:C57BL/6J mice initiated 45%high fat diet at 8 weeks of age.After 6 weeks of diet,animals were divided into moderate(MOD)or high intensity interval training interventions(HIIT),animals were further divided into autophagy inhibition or vehicle conditions(n=10/group).Animals exercised and autophagy was inhibited 3X/week by NSC185058 injections,thereby blocking autophagosome formation.Interventions continued for 4 weeks.Results:High fat diet impaired glucose handling~17%;exercise interventions normalized glucoregulation to prehigh fat diet levels,without differences between any interventions.High fat diet induced~25%decrease in aerobic capacity,which returned to baseline after exercise interventions,with no differences between any interventions.No effects of autophagy inhibition were noted.Conclusions:HIIT and MOD training confer similar health-related adaptations.

关键词： Insulin resistance exercise capacity Glucose tolerance Obesity

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Capsule endoscopy and panendoscopy:A journey to the future of gastrointestinal endoscopy

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World Journal of Gastroenterology 2024年第10期30卷 1270-1279页

作者： Bruno rosa JoséCotter Department of Gastroenterology Hospital da Senhora da OliveiraGuimarães 4835-044Portugal Life and Health Sciences Research Institute School of MedicineUniversity of MinhoBraga 4710-057Portugal ICVS/3B's PT Government Associate LaboratoryBraga 4710-057Portugal

In 2000,the small bowel capsule revolutionized the management of patients with small bowel disorders.Currently,the technological development achieved by the new models of double-headed endoscopic capsules,as miniaturized devices to evaluate the small bowel and colon[pan-intestinal capsule endoscopy(PCe)],makes this non-invasive procedure a disruptive concept for the management of patients with digestive disorders.This technology is expected to identify which patients will require conventional invasive endoscopic procedures(colonoscopy or balloon-assisted enteroscopy),based on the lesions detected by the capsule,i.e.,those with an indication for biopsies or endoscopic treatment.The use of PCe in patients with inflammatory bowel diseases,namely Crohn’s disease,as well as in patients with iron deficiency anaemia and/or overt gastrointestinal(GI)bleeding,after a non-diagnostic upper endoscopy(esophagogastroduodenoscopy),enables an effective,safe and comfortable way to identify patients with relevant lesions,who should undergo subsequent invasive endoscopic procedures.The recent development of magnetically controlled capsule endoscopy to evaluate the upper GI tract,is a further step towards the possibility of an entirely non-invasive assessment of all the segments of the digestive tract,from mouth-to-anus,meeting the expectations of the early developers of capsule endoscopy.

关键词： Non-invasive endoscopy Panendoscopy Magnetically controlled capsule endoscopy Crohn’s disease Digestive bleeding

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Interactions between maternal parity and feed additives drive the composition of pig gut microbiomes in the post‑weaning period

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Journal of Animal Science and Biotechnology 2024年第3期15卷 1241-1257页

作者： Kayla Law eduardo rosa Medina Garcia Chad Hastad Deborah Murray Pedro e.Urriola Andres Gomez Department of Animal Science University of Minnesota1364 Eckles AvenueSaint PaulMN 55108USA New Fashion Pork 164 Industrial ParkwayJacksonMN 56143USA

Background Nursery pigs undergo stressors in the post-weaning period that result in production and welfare chal-lenges.These challenges disproportionately impact the offspring of primiparous sows compared to those of mul-tiparous counterparts.Little is known regarding potential interactions between parity and feed additives in the post-weaning period and their effects on nursery pig microbiomes.Therefore,the objective of this study was to investigate the effects of maternal parity on sow and offspring microbiomes and the influence of sow parity on pig fecal microbi-ome and performance in response to a prebiotic post-weaning.At weaning,piglets were allotted into three treat-ment groups:a standard nursery diet including pharmacological doses of Zn and Cu(Con),a group fed a commercial prebiotic only(Preb)based on an Aspergillus oryzae fermentation extract,and a group fed the same prebiotic plus Zn and Cu(Preb+ZnCu).Results Although there were no differences in vaginal microbiome composition between primiparous and mul-tiparous sows,fecal microbiome composition was different(R^(2)=0.02,P=0.03).The fecal microbiomes of primiparous offspring displayed significantly higher bacterial diversity compared to multiparous offspring at d 0 and d 21 post-weaning(Perences in community composition observed at d 21(R^(2)=0.03,P=0.04).When analyzing the effects of maternal parity within each treatment,only the Preb diet triggered significant microbiome distinc-tions between primiparous and multiparous offspring(d 21:R^(2)=0.13,P=0.01;d 42:R^(2)=0.19,P=0.001).Composi-tional differences in pig fecal microbiomes between treatments were observed only at d 21(R^(2)=0.12,P=0.001).Pigs in the Con group gained significantly more weight throughout the nursery period when compared to those in the Preb+ZnCu group.Conclusions Nursery pig gut microbiome composition was influenced by supplementation with an Aspergillus oryzae fermentation extract,with varying effects on performance when combined with pharmacological levels of Zn

关键词： Aspergillus prebiotic Copper Feed additives Maternal Nursery pig microbiome Parity Swine microbiome Trace minerals Zinc

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Restimate:Recovery estimation Tool for Resilience Planning

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Journal of Safety Science and Resilience 2024年第1期5卷 47-63页

作者： Scott Miles megan Ly Nick Terry Youngjun Choe Department of Human Centered Design&engineering Campus Box 352315University of WashingtonSeattleWA 98195United States of America Department of Industrial&Systems engineering Box 352650University of WashingtonSeattleWA 98195United States of America

The U.S.National Institute of Standards and Technology(NIST)published the Community Resilience Planning Guide in 2016.The NIST Guide advocates for a participatory process for developing a performance measurement framework for the jurisdiction’s resilience against a scenario hazard.The framework centers around tables of expected and desired recovery times for selected community assets,such as electricity,water,and natural gas infrastructures.The NIST Guide does not provide a method for estimating the expected recovery times.However,building high-fidelity computer models for such estimations requires substantial resources that even larger ju-risdictions cannot cost-justify.The most promising approach to recovery time estimation is to systematically use data elicited from people to tap into the wisdom of the(knowledgeable)crowd.This paper describes a novel research-through-design project to enable the computer-supported elicitation of recovery time series data.This work is the first in the literature to examine people’s ability to estimate recovery curves and how design in-fluences such estimations.Its main contribution to resilience planning is three-fold:development of a new elicitation tool called Restimate,understanding its potential user base,and providing insights into how it can facilitate resilience planning.Restimate is the first tool to enable evidence-based expert elicitation in any community with limited resources for resilience planning.Beyond resilience planning,those who facilitate high-stakes planning activities under large uncertainties(e.g.,mission-critical system design and planning)will benefit from a similar research-through-design process.

关键词： expert elicitation disaster natural hazard infrastructure community resilience restoration user-centered design computer-supported cooperative work

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The effect of diet-induced obesity on extracellular matrix remodeling during skeletal muscle regeneration

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Sports Medicine and Health Science 2021年第4期3卷 212-217页

作者： J.William Deaver eleanor R.Schrems Lemuel A.Brown Wesley A.Haynie Richard A.Perry Jr. megan e.rosa-caldwell Michelle A.Tedrowe Nicholas P.Greene Tyrone A.Washington exercise Muscle Biology Laboratory Exercise Science Research CenterDepartment of HealthHuman Performance and RecreationUniversity of ArkansasFayettevilleAR72701USA Cachexia Research Laboratory Exercise Science Research CenterDepartment of HealthHuman Performance and RecreationUniversity of ArkansasFayettevilleAR72701USA

Diet-induced obesity has previously been shown to occur with the concomitant rise in the expression of proin-flammatory cytokines and increases in collagen deposition.While it has been known that the regenerative process of skeletal muscle is altered in obese mice following an acute muscle injury,we sought to examine differences in the expression of various markers of extracellular matrix remodeling and repair.Our laboratory has previously reported an impaired inflammatory and protein synthetic signaling in these mice that may contribute negatively to the muscle regenerative process.To expand upon this previous investigation,tissues from these animals un-derwent further analysis to determine the extent of changes to the regenerative response within the extracellular matrix,including transcriptional changes in CollagenⅠ,CollagenⅢ,and Fibronectin.Here,we show that the expression of CollagenⅢ:Ⅰis significantly increased at 3-days post-injury in obese injured animals compared to lean injured animals(p=0.0338),and by 28-days the obese injured animals exhibit a significantly lower CollagenⅢ:Ⅰthan their lean injured counterparts(p=0.0035).We demonstrate an impaired response to an acute muscle injury in obese mice when compared with lean counterparts.However,further studies are required to elucidate translational consequences of these changes,as well as to determine any causative mechanisms that may be driving this effect.

关键词： Diet induced obesity extracellular matrix remodeling Skeletal muscle

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