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Hepatic glucagon action is essential for exercise-induced reversal of mouse fatty liver.

Berglund ED, Lustig DG, Baheza RA, Hasenour CM, Lee-Young RS, Donahue EP, Lynes SE, Swift LL, Charron MJ, Damon BM, Wasserman DH - Diabetes (2011)

Bottom Line: Exercise is an effective intervention to treat fatty liver.Here we tested the hypothesis that exercise requires hepatic glucagon action to reduce fatty liver.These findings suggest that therapies that use antagonism of hepatic glucagon action to reduce blood glucose may interfere with the ability of exercise and perhaps other interventions to positively affect fatty liver.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. berglunde@gmail.com

ABSTRACT

Objective: Exercise is an effective intervention to treat fatty liver. However, the mechanism(s) that underlie exercise-induced reductions in fatty liver are unclear. Here we tested the hypothesis that exercise requires hepatic glucagon action to reduce fatty liver.

Research design and methods: C57BL/6 mice were fed high-fat diet (HFD) and assessed using magnetic resonance, biochemical, and histological techniques to establish a timeline for fatty liver development over 20 weeks. Glucagon receptor (gcgr(-/-)) and wild-type (gcgr(+/+)) littermate mice were subsequently fed HFD to provoke moderate fatty liver and then performed either 10 or 6 weeks of running wheel or treadmill exercise, respectively.

Results: Exercise reverses progression of HFD-induced fatty liver in gcgr(+/+) mice. Remarkably, such changes are absent in gcgr(-/-) mice, thus confirming the hypothesis that exercise-stimulated hepatic glucagon receptor activation is critical to reduce HFD-induced fatty liver.

Conclusions: These findings suggest that therapies that use antagonism of hepatic glucagon action to reduce blood glucose may interfere with the ability of exercise and perhaps other interventions to positively affect fatty liver.

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Related in: MedlinePlus

Assessment of HFD-induced fatty liver in male BL6 mice using MR (A) or Oil Red O (B) staining (n = 7–8 mice/group). Mice were fed HFD or chow at 6 weeks of age and killed at indicated time points. Representative images (C and D) and correlation coefficients (E and F). *P < 0.05 compared with chow controls. †P < 0.05 compared with the previous time point. (A high-quality digital representation of this figure is available in the online issue.)
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Figure 2: Assessment of HFD-induced fatty liver in male BL6 mice using MR (A) or Oil Red O (B) staining (n = 7–8 mice/group). Mice were fed HFD or chow at 6 weeks of age and killed at indicated time points. Representative images (C and D) and correlation coefficients (E and F). *P < 0.05 compared with chow controls. †P < 0.05 compared with the previous time point. (A high-quality digital representation of this figure is available in the online issue.)

Mentions: In agreement with biochemical assessments, MR and histology found that liver fat in mice fed HFD increased over time and was elevated compared with chow controls at 8, 12, and 20 weeks (Fig. 2A–D). Hepatic fat assessed by MR and histology in chow controls were <5% at all points (Fig. 2A and B). Assessment of hepatic fat by MR correlated well with biochemical measurements (r2 = 0.86). Histological assessment did not correlate as well (r2 = 0.62) (Fig. 2E and F).


Hepatic glucagon action is essential for exercise-induced reversal of mouse fatty liver.

Berglund ED, Lustig DG, Baheza RA, Hasenour CM, Lee-Young RS, Donahue EP, Lynes SE, Swift LL, Charron MJ, Damon BM, Wasserman DH - Diabetes (2011)

Assessment of HFD-induced fatty liver in male BL6 mice using MR (A) or Oil Red O (B) staining (n = 7–8 mice/group). Mice were fed HFD or chow at 6 weeks of age and killed at indicated time points. Representative images (C and D) and correlation coefficients (E and F). *P < 0.05 compared with chow controls. †P < 0.05 compared with the previous time point. (A high-quality digital representation of this figure is available in the online issue.)
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3198076&req=5

Figure 2: Assessment of HFD-induced fatty liver in male BL6 mice using MR (A) or Oil Red O (B) staining (n = 7–8 mice/group). Mice were fed HFD or chow at 6 weeks of age and killed at indicated time points. Representative images (C and D) and correlation coefficients (E and F). *P < 0.05 compared with chow controls. †P < 0.05 compared with the previous time point. (A high-quality digital representation of this figure is available in the online issue.)
Mentions: In agreement with biochemical assessments, MR and histology found that liver fat in mice fed HFD increased over time and was elevated compared with chow controls at 8, 12, and 20 weeks (Fig. 2A–D). Hepatic fat assessed by MR and histology in chow controls were <5% at all points (Fig. 2A and B). Assessment of hepatic fat by MR correlated well with biochemical measurements (r2 = 0.86). Histological assessment did not correlate as well (r2 = 0.62) (Fig. 2E and F).

Bottom Line: Exercise is an effective intervention to treat fatty liver.Here we tested the hypothesis that exercise requires hepatic glucagon action to reduce fatty liver.These findings suggest that therapies that use antagonism of hepatic glucagon action to reduce blood glucose may interfere with the ability of exercise and perhaps other interventions to positively affect fatty liver.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. berglunde@gmail.com

ABSTRACT

Objective: Exercise is an effective intervention to treat fatty liver. However, the mechanism(s) that underlie exercise-induced reductions in fatty liver are unclear. Here we tested the hypothesis that exercise requires hepatic glucagon action to reduce fatty liver.

Research design and methods: C57BL/6 mice were fed high-fat diet (HFD) and assessed using magnetic resonance, biochemical, and histological techniques to establish a timeline for fatty liver development over 20 weeks. Glucagon receptor (gcgr(-/-)) and wild-type (gcgr(+/+)) littermate mice were subsequently fed HFD to provoke moderate fatty liver and then performed either 10 or 6 weeks of running wheel or treadmill exercise, respectively.

Results: Exercise reverses progression of HFD-induced fatty liver in gcgr(+/+) mice. Remarkably, such changes are absent in gcgr(-/-) mice, thus confirming the hypothesis that exercise-stimulated hepatic glucagon receptor activation is critical to reduce HFD-induced fatty liver.

Conclusions: These findings suggest that therapies that use antagonism of hepatic glucagon action to reduce blood glucose may interfere with the ability of exercise and perhaps other interventions to positively affect fatty liver.

Show MeSH
Related in: MedlinePlus