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Increasing muscle mass improves vascular function in obese (db/db) mice.

Qiu S, Mintz JD, Salet CD, Han W, Giannis A, Chen F, Yu Y, Su Y, Fulton DJ, Stepp DW - J Am Heart Assoc (2014)

Bottom Line: Inactivity is associated with a loss of muscle mass, which is also reversed with isometric exercise training.This impairment was improved by superoxide dismutase mimic Tempol.This improvement was blunted by nitric oxide (NO) synthase inhibitor l-NG-nitroarginine methyl ester (l-NAME).

View Article: PubMed Central - PubMed

Affiliation: Vascular Biology Center and Department of Physiology, Georgia Regents University, Augusta, GA, Germany (S.Q., J.D.M., C.D.S., W.H., A.G., F.C., Y.Y., Y.S., D.J.F., D.W.S.).

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The myostatin gene significantly increased muscle mass in both lean and obese (db/db) mice. A, Increased skeletal muscle mass by deletion of myostatin in both lean and obese (db/db) mice. B, Axial leg MRI scans. Muscle is shown in gray; adipose tissue is shown in white. C, Sections of distal hindlimbs (TA muscle) stained with hematoxylin and eosin (×200); bars represent 50 μm. A through C, left to right: lean, lean myostatin−/−, db/db, and db/db myostatin−/−. D, Tibialis anterior muscle weight of all groups of mice. E, Tibialis anterior myofiber diameter. Data reported here as representative hematoxylin and eosin–stained cryosections, and as box and whisker plots comprising minimum, median, and maximum value for myofiber diameter. Data are shown as mean±SEM (A through E: n=8). *P<0.05; ***P<0.001, lean myostatin−/− versus lean or db/db myostatin−/− versus db/db. #P<0.05; ##P<0.01, db/db versus lean or db/db myostatin−/− versus lean myostatin−/−. db/db myostatin−/− indicates mice lacking both myostatin and leptin receptor; db/db, obese leptin receptor‐deficient mice heterozygous for myostastin; lean myostatin−/−, myostatin‐ mice heterozygous for leptin receptors; lean, lean dual heterozygotes; MRI, magnetic resonance imaging; TA, tibialis anterior.
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fig03: The myostatin gene significantly increased muscle mass in both lean and obese (db/db) mice. A, Increased skeletal muscle mass by deletion of myostatin in both lean and obese (db/db) mice. B, Axial leg MRI scans. Muscle is shown in gray; adipose tissue is shown in white. C, Sections of distal hindlimbs (TA muscle) stained with hematoxylin and eosin (×200); bars represent 50 μm. A through C, left to right: lean, lean myostatin−/−, db/db, and db/db myostatin−/−. D, Tibialis anterior muscle weight of all groups of mice. E, Tibialis anterior myofiber diameter. Data reported here as representative hematoxylin and eosin–stained cryosections, and as box and whisker plots comprising minimum, median, and maximum value for myofiber diameter. Data are shown as mean±SEM (A through E: n=8). *P<0.05; ***P<0.001, lean myostatin−/− versus lean or db/db myostatin−/− versus db/db. #P<0.05; ##P<0.01, db/db versus lean or db/db myostatin−/− versus lean myostatin−/−. db/db myostatin−/− indicates mice lacking both myostatin and leptin receptor; db/db, obese leptin receptor‐deficient mice heterozygous for myostastin; lean myostatin−/−, myostatin‐ mice heterozygous for leptin receptors; lean, lean dual heterozygotes; MRI, magnetic resonance imaging; TA, tibialis anterior.

Mentions: The effect of myostatin on muscle mass is depicted in Figure 3 in a number of ways. In Figure 3A, lower‐limb muscles from cadaver mice are shown for the purpose of illustration. Limb mass was observably larger after myostatin deletion than those of lean and obese control mice. Figure 3B shows the axial T1‐weighted cross‐section of the lower‐limb muscles by MRI in anesthetized mice. Obese mice showed a decreased cross‐section area of lower‐limb muscles, whereas deletion of myostatin increased muscles in both lean and obese mice. For Figure 3D, individual muscles were dissected free and weighed for quantitative assessment. Deletion of myostatin significantly increased tibialis anterior (TA) in both lean and db/db mice, essentially restoring obese muscle mass back to lean levels. Similar results were observed in the gastrocnemius (GS), gluteal, and triceps muscles (Table 3). To determine the anatomic basis of increased muscle mass, TA muscle fiber size was assessed histologically with H&E‐stained cryosections (representative examples in Figure 3C) as well as as box and whisker plots comprising minimum, median, and maximum value for muscle fiber diameter (Figure 3E). Obese mice showed decreased TA muscle fiber size, compared to lean mice (28.52±0.25 vs. 43.29±1.01 μm; P<0.05), deletion of myostatin increased TA muscle fiber size in both lean and db/db mice (lean myostatin−/−: 50.06±1.02 μm; db/db myostatin−/−: 46.08±0.96 μm; P<0.05).


Increasing muscle mass improves vascular function in obese (db/db) mice.

Qiu S, Mintz JD, Salet CD, Han W, Giannis A, Chen F, Yu Y, Su Y, Fulton DJ, Stepp DW - J Am Heart Assoc (2014)

The myostatin gene significantly increased muscle mass in both lean and obese (db/db) mice. A, Increased skeletal muscle mass by deletion of myostatin in both lean and obese (db/db) mice. B, Axial leg MRI scans. Muscle is shown in gray; adipose tissue is shown in white. C, Sections of distal hindlimbs (TA muscle) stained with hematoxylin and eosin (×200); bars represent 50 μm. A through C, left to right: lean, lean myostatin−/−, db/db, and db/db myostatin−/−. D, Tibialis anterior muscle weight of all groups of mice. E, Tibialis anterior myofiber diameter. Data reported here as representative hematoxylin and eosin–stained cryosections, and as box and whisker plots comprising minimum, median, and maximum value for myofiber diameter. Data are shown as mean±SEM (A through E: n=8). *P<0.05; ***P<0.001, lean myostatin−/− versus lean or db/db myostatin−/− versus db/db. #P<0.05; ##P<0.01, db/db versus lean or db/db myostatin−/− versus lean myostatin−/−. db/db myostatin−/− indicates mice lacking both myostatin and leptin receptor; db/db, obese leptin receptor‐deficient mice heterozygous for myostastin; lean myostatin−/−, myostatin‐ mice heterozygous for leptin receptors; lean, lean dual heterozygotes; MRI, magnetic resonance imaging; TA, tibialis anterior.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4309080&req=5

fig03: The myostatin gene significantly increased muscle mass in both lean and obese (db/db) mice. A, Increased skeletal muscle mass by deletion of myostatin in both lean and obese (db/db) mice. B, Axial leg MRI scans. Muscle is shown in gray; adipose tissue is shown in white. C, Sections of distal hindlimbs (TA muscle) stained with hematoxylin and eosin (×200); bars represent 50 μm. A through C, left to right: lean, lean myostatin−/−, db/db, and db/db myostatin−/−. D, Tibialis anterior muscle weight of all groups of mice. E, Tibialis anterior myofiber diameter. Data reported here as representative hematoxylin and eosin–stained cryosections, and as box and whisker plots comprising minimum, median, and maximum value for myofiber diameter. Data are shown as mean±SEM (A through E: n=8). *P<0.05; ***P<0.001, lean myostatin−/− versus lean or db/db myostatin−/− versus db/db. #P<0.05; ##P<0.01, db/db versus lean or db/db myostatin−/− versus lean myostatin−/−. db/db myostatin−/− indicates mice lacking both myostatin and leptin receptor; db/db, obese leptin receptor‐deficient mice heterozygous for myostastin; lean myostatin−/−, myostatin‐ mice heterozygous for leptin receptors; lean, lean dual heterozygotes; MRI, magnetic resonance imaging; TA, tibialis anterior.
Mentions: The effect of myostatin on muscle mass is depicted in Figure 3 in a number of ways. In Figure 3A, lower‐limb muscles from cadaver mice are shown for the purpose of illustration. Limb mass was observably larger after myostatin deletion than those of lean and obese control mice. Figure 3B shows the axial T1‐weighted cross‐section of the lower‐limb muscles by MRI in anesthetized mice. Obese mice showed a decreased cross‐section area of lower‐limb muscles, whereas deletion of myostatin increased muscles in both lean and obese mice. For Figure 3D, individual muscles were dissected free and weighed for quantitative assessment. Deletion of myostatin significantly increased tibialis anterior (TA) in both lean and db/db mice, essentially restoring obese muscle mass back to lean levels. Similar results were observed in the gastrocnemius (GS), gluteal, and triceps muscles (Table 3). To determine the anatomic basis of increased muscle mass, TA muscle fiber size was assessed histologically with H&E‐stained cryosections (representative examples in Figure 3C) as well as as box and whisker plots comprising minimum, median, and maximum value for muscle fiber diameter (Figure 3E). Obese mice showed decreased TA muscle fiber size, compared to lean mice (28.52±0.25 vs. 43.29±1.01 μm; P<0.05), deletion of myostatin increased TA muscle fiber size in both lean and db/db mice (lean myostatin−/−: 50.06±1.02 μm; db/db myostatin−/−: 46.08±0.96 μm; P<0.05).

Bottom Line: Inactivity is associated with a loss of muscle mass, which is also reversed with isometric exercise training.This impairment was improved by superoxide dismutase mimic Tempol.This improvement was blunted by nitric oxide (NO) synthase inhibitor l-NG-nitroarginine methyl ester (l-NAME).

View Article: PubMed Central - PubMed

Affiliation: Vascular Biology Center and Department of Physiology, Georgia Regents University, Augusta, GA, Germany (S.Q., J.D.M., C.D.S., W.H., A.G., F.C., Y.Y., Y.S., D.J.F., D.W.S.).

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Related in: MedlinePlus