{"title":"大鼠全身和肌肉铁代谢对极端缺乏运动的适应性的性别相似性和差异性","authors":"Mathieu Horeau, Melissa Delalande, Martine Ropert, Patricia Leroyer, Brice Martin, Luz Orfila, Olivier Loréal, Frédéric Derbré","doi":"10.1002/jcsm.13547","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Previous data in humans suggest that extreme physical inactivity (EPI) affects iron metabolism differently between sexes. Our objective was to deepen the underlying mechanisms by studying rats of both sexes exposed to hindlimb unloading (HU), the reference experimental model mimicking EPI.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Eight-week-old male and female Wistar rats were assigned to control (CTL) or hindlimb unloading (HU) conditions (<i>n</i> = 12/group). After 7 days of HU, serum, liver, spleen, and soleus muscle were removed. Iron parameters were measured in serum samples, and ICP-MS was used to quantify iron in tissues. Iron metabolism genes and proteins were analysed by RT-qPCR and Western blot.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Compared with control males, control females exhibited higher iron concentrations in serum (+43.3%, <i>p</i> < 0.001), liver (LIC; +198%, <i>P</i> < 0.001), spleen (SIC; +76.1%, <i>P</i> < 0.001), and transferrin saturation (TS) in serum (+53.3%, <i>P</i> < 0.001), contrasting with previous observations in humans. HU rat males, but not females, exhibited an increase of LIC (+54% <i>P</i> < 0.001) and SIC (+30.1%, <i>P</i> = 0.023), along with a rise of H-ferritin protein levels (+60.9% and +134%, respectively, in liver and spleen; <i>P</i> < 0.05) and a decrease of TFRC protein levels (−36%; −50%, respectively, <i>P</i> < 0.05). HU males also exhibited an increase of splenic <i>HO-1</i> and <i>NRF2</i> mRNA levels, (<i>p</i> < 0.001), as well as HU females (<i>P</i> < 0.001). Concomitantly to muscle atrophy observed in HU animals, the iron concentration increased in soleus in females (+26.7, <i>P</i> = 0.004) while only a trend is observed in males (+17.5%, <i>P</i> = 0.088). In addition, the H-ferritin and myoglobin protein levels in soleus were increased in males (+748%, <i>P</i> < 0.001, +22%, <i>P</i> = 0.011, respectively) and in females (+369%, <i>P</i> < 0.001, +21.9%, <i>P</i> = 0.007, respectively), whereas TFRC and ferroportin (FPN) protein levels were reduced in males (−68.9%, <i>P</i> < 0.001, −76.8%, <i>P</i> < 0.001, respectively) and females (−75.9%, <i>P</i> < 0.001, −62.9%, <i>P</i> < 0.001, respectively). Interestingly, in both sexes, heme exporter FLVCR1 mRNA increased in soleus, while protein levels decreased (−39.9% for males <i>P</i> = 0.010 and −49.1% for females <i>P</i> < 0.001).</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>Taken together, these data support that, in rats (1) extreme physical inactivity differently impacts the distribution of iron in both sexes, (2) splenic erythrophagocytosis could play a role in this iron misdistribution. The higher iron concentrations in atrophied soleus from both sexes are associated with a decoupling between the increase in iron storage proteins (i.e., ferritin and myoglobin) and the decrease in levels of iron export proteins (i.e., FPN and FLVCR1), thus supporting an iron sequestration in skeletal muscle under extreme physical inactivity.</p>\n </section>\n </div>","PeriodicalId":48911,"journal":{"name":"Journal of Cachexia Sarcopenia and Muscle","volume":"15 5","pages":"1989-1998"},"PeriodicalIF":9.4000,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13547","citationCount":"0","resultStr":"{\"title\":\"Sex similarities and divergences in systemic and muscle iron metabolism adaptations to extreme physical inactivity in rats\",\"authors\":\"Mathieu Horeau, Melissa Delalande, Martine Ropert, Patricia Leroyer, Brice Martin, Luz Orfila, Olivier Loréal, Frédéric Derbré\",\"doi\":\"10.1002/jcsm.13547\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>Previous data in humans suggest that extreme physical inactivity (EPI) affects iron metabolism differently between sexes. Our objective was to deepen the underlying mechanisms by studying rats of both sexes exposed to hindlimb unloading (HU), the reference experimental model mimicking EPI.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>Eight-week-old male and female Wistar rats were assigned to control (CTL) or hindlimb unloading (HU) conditions (<i>n</i> = 12/group). After 7 days of HU, serum, liver, spleen, and soleus muscle were removed. Iron parameters were measured in serum samples, and ICP-MS was used to quantify iron in tissues. Iron metabolism genes and proteins were analysed by RT-qPCR and Western blot.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Compared with control males, control females exhibited higher iron concentrations in serum (+43.3%, <i>p</i> < 0.001), liver (LIC; +198%, <i>P</i> < 0.001), spleen (SIC; +76.1%, <i>P</i> < 0.001), and transferrin saturation (TS) in serum (+53.3%, <i>P</i> < 0.001), contrasting with previous observations in humans. HU rat males, but not females, exhibited an increase of LIC (+54% <i>P</i> < 0.001) and SIC (+30.1%, <i>P</i> = 0.023), along with a rise of H-ferritin protein levels (+60.9% and +134%, respectively, in liver and spleen; <i>P</i> < 0.05) and a decrease of TFRC protein levels (−36%; −50%, respectively, <i>P</i> < 0.05). HU males also exhibited an increase of splenic <i>HO-1</i> and <i>NRF2</i> mRNA levels, (<i>p</i> < 0.001), as well as HU females (<i>P</i> < 0.001). Concomitantly to muscle atrophy observed in HU animals, the iron concentration increased in soleus in females (+26.7, <i>P</i> = 0.004) while only a trend is observed in males (+17.5%, <i>P</i> = 0.088). In addition, the H-ferritin and myoglobin protein levels in soleus were increased in males (+748%, <i>P</i> < 0.001, +22%, <i>P</i> = 0.011, respectively) and in females (+369%, <i>P</i> < 0.001, +21.9%, <i>P</i> = 0.007, respectively), whereas TFRC and ferroportin (FPN) protein levels were reduced in males (−68.9%, <i>P</i> < 0.001, −76.8%, <i>P</i> < 0.001, respectively) and females (−75.9%, <i>P</i> < 0.001, −62.9%, <i>P</i> < 0.001, respectively). Interestingly, in both sexes, heme exporter FLVCR1 mRNA increased in soleus, while protein levels decreased (−39.9% for males <i>P</i> = 0.010 and −49.1% for females <i>P</i> < 0.001).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>Taken together, these data support that, in rats (1) extreme physical inactivity differently impacts the distribution of iron in both sexes, (2) splenic erythrophagocytosis could play a role in this iron misdistribution. The higher iron concentrations in atrophied soleus from both sexes are associated with a decoupling between the increase in iron storage proteins (i.e., ferritin and myoglobin) and the decrease in levels of iron export proteins (i.e., FPN and FLVCR1), thus supporting an iron sequestration in skeletal muscle under extreme physical inactivity.</p>\\n </section>\\n </div>\",\"PeriodicalId\":48911,\"journal\":{\"name\":\"Journal of Cachexia Sarcopenia and Muscle\",\"volume\":\"15 5\",\"pages\":\"1989-1998\"},\"PeriodicalIF\":9.4000,\"publicationDate\":\"2024-07-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13547\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Cachexia Sarcopenia and Muscle\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/jcsm.13547\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GERIATRICS & GERONTOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Cachexia Sarcopenia and Muscle","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jcsm.13547","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GERIATRICS & GERONTOLOGY","Score":null,"Total":0}
Sex similarities and divergences in systemic and muscle iron metabolism adaptations to extreme physical inactivity in rats
Background
Previous data in humans suggest that extreme physical inactivity (EPI) affects iron metabolism differently between sexes. Our objective was to deepen the underlying mechanisms by studying rats of both sexes exposed to hindlimb unloading (HU), the reference experimental model mimicking EPI.
Methods
Eight-week-old male and female Wistar rats were assigned to control (CTL) or hindlimb unloading (HU) conditions (n = 12/group). After 7 days of HU, serum, liver, spleen, and soleus muscle were removed. Iron parameters were measured in serum samples, and ICP-MS was used to quantify iron in tissues. Iron metabolism genes and proteins were analysed by RT-qPCR and Western blot.
Results
Compared with control males, control females exhibited higher iron concentrations in serum (+43.3%, p < 0.001), liver (LIC; +198%, P < 0.001), spleen (SIC; +76.1%, P < 0.001), and transferrin saturation (TS) in serum (+53.3%, P < 0.001), contrasting with previous observations in humans. HU rat males, but not females, exhibited an increase of LIC (+54% P < 0.001) and SIC (+30.1%, P = 0.023), along with a rise of H-ferritin protein levels (+60.9% and +134%, respectively, in liver and spleen; P < 0.05) and a decrease of TFRC protein levels (−36%; −50%, respectively, P < 0.05). HU males also exhibited an increase of splenic HO-1 and NRF2 mRNA levels, (p < 0.001), as well as HU females (P < 0.001). Concomitantly to muscle atrophy observed in HU animals, the iron concentration increased in soleus in females (+26.7, P = 0.004) while only a trend is observed in males (+17.5%, P = 0.088). In addition, the H-ferritin and myoglobin protein levels in soleus were increased in males (+748%, P < 0.001, +22%, P = 0.011, respectively) and in females (+369%, P < 0.001, +21.9%, P = 0.007, respectively), whereas TFRC and ferroportin (FPN) protein levels were reduced in males (−68.9%, P < 0.001, −76.8%, P < 0.001, respectively) and females (−75.9%, P < 0.001, −62.9%, P < 0.001, respectively). Interestingly, in both sexes, heme exporter FLVCR1 mRNA increased in soleus, while protein levels decreased (−39.9% for males P = 0.010 and −49.1% for females P < 0.001).
Conclusions
Taken together, these data support that, in rats (1) extreme physical inactivity differently impacts the distribution of iron in both sexes, (2) splenic erythrophagocytosis could play a role in this iron misdistribution. The higher iron concentrations in atrophied soleus from both sexes are associated with a decoupling between the increase in iron storage proteins (i.e., ferritin and myoglobin) and the decrease in levels of iron export proteins (i.e., FPN and FLVCR1), thus supporting an iron sequestration in skeletal muscle under extreme physical inactivity.
期刊介绍:
The Journal of Cachexia, Sarcopenia and Muscle is a peer-reviewed international journal dedicated to publishing materials related to cachexia and sarcopenia, as well as body composition and its physiological and pathophysiological changes across the lifespan and in response to various illnesses from all fields of life sciences. The journal aims to provide a reliable resource for professionals interested in related research or involved in the clinical care of affected patients, such as those suffering from AIDS, cancer, chronic heart failure, chronic lung disease, liver cirrhosis, chronic kidney failure, rheumatoid arthritis, or sepsis.