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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

HFD-induced fatty liver time course in male BL6 mice. Mice were fed HFD or chow at 6 weeks of age and killed at indicated time points (n = 7–8 mice/group). *P < 0.05 compared with chow controls. †P < 0.05 compared with the previous time point.
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Figure 1: HFD-induced fatty liver time course in male BL6 mice. Mice were fed HFD or chow at 6 weeks of age and killed at indicated time points (n = 7–8 mice/group). *P < 0.05 compared with chow controls. †P < 0.05 compared with the previous time point.

Mentions: At 6 weeks of age, BL6 mice were fed chow or HFD to assess fatty liver. Whole-body fat mass increased in mice fed HFD beginning at 4 weeks compared with the preceding time point and duration-matched chow controls (Fig. 1A). Whole-body fat mass was unchanged in chow mice over time (Fig. 1A). Whole-body lean mass in mice fed HFD progressively increased and was greater than chow controls at 4, 12, and 20 weeks (Fig. 1B). Whole-body lean mass also progressively increased in chow controls (Fig. 1B). Liver mass in mice fed HFD was unchanged at all points except 20 weeks and did not vary in chow mice (Fig. 1C). Hepatic TGs, DGs, and CEs in mice fed HFD increased between each measurement after 4 weeks and versus chow controls (Fig. 1D–F). In contrast, hepatic PLs in mice fed HFD were comparable to chow controls at 2, 4, and 8 weeks but were decreased at 12 and 20 weeks (Fig. 1G). Hepatic TGs, DGs, CEs, and PLs were unchanged in chow mice (Fig. 1D–G).


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)

HFD-induced fatty liver time course in male BL6 mice. Mice were fed HFD or chow at 6 weeks of age and killed at indicated time points (n = 7–8 mice/group). *P < 0.05 compared with chow controls. †P < 0.05 compared with the previous time point.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

Figure 1: HFD-induced fatty liver time course in male BL6 mice. Mice were fed HFD or chow at 6 weeks of age and killed at indicated time points (n = 7–8 mice/group). *P < 0.05 compared with chow controls. †P < 0.05 compared with the previous time point.
Mentions: At 6 weeks of age, BL6 mice were fed chow or HFD to assess fatty liver. Whole-body fat mass increased in mice fed HFD beginning at 4 weeks compared with the preceding time point and duration-matched chow controls (Fig. 1A). Whole-body fat mass was unchanged in chow mice over time (Fig. 1A). Whole-body lean mass in mice fed HFD progressively increased and was greater than chow controls at 4, 12, and 20 weeks (Fig. 1B). Whole-body lean mass also progressively increased in chow controls (Fig. 1B). Liver mass in mice fed HFD was unchanged at all points except 20 weeks and did not vary in chow mice (Fig. 1C). Hepatic TGs, DGs, and CEs in mice fed HFD increased between each measurement after 4 weeks and versus chow controls (Fig. 1D–F). In contrast, hepatic PLs in mice fed HFD were comparable to chow controls at 2, 4, and 8 weeks but were decreased at 12 and 20 weeks (Fig. 1G). Hepatic TGs, DGs, CEs, and PLs were unchanged in chow mice (Fig. 1D–G).

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