Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2003 Sep 1;551(Pt 2):673-82.
doi: 10.1113/jphysiol.2003.045591. Epub 2003 Jun 18.

Suppression of skeletal muscle lipoprotein lipase activity during physical inactivity: a molecular reason to maintain daily low-intensity activity

Lionel Bey  1 , Marc T Hamilton
Affiliations

Suppression of skeletal muscle lipoprotein lipase activity during physical inactivity: a molecular reason to maintain daily low-intensity activity

Lionel Bey et al. J Physiol. .

Abstract

We have examined the regulation of lipoprotein lipase (LPL) activity in skeletal muscle during physical inactivity in comparison to low-intensity contractile activity of ambulatory controls. From studies acutely preventing ambulatory activity of one or both the hindlimbs in rats, it was shown that approximately 90-95 % of the heparin-releasable (HR) LPL activity normally present in rat muscle with ambulatory activity is lost, and thus dependent on local contractile activity. Similarly, approximately 95 % of the differences in LPL activity between muscles of different fibre types was dependent on ambulatory activity. The robustness of the finding that physical inactivity significantly decreases muscle LPL activity was evident from confirmatory studies with different models of inactivity, in many rats and mice, both sexes, three muscle types and during both acute and chronic (11 days) treatment. Inactivity caused a local reduction of plasma [3H]triglyceride uptake into muscle and a decrease in high density lipoprotein cholesterol concentration. LPL mRNA was not differentially expressed between ambulatory controls and either the acutely or chronically inactive groups. Instead, the process involved a rapid loss of the HR-LPL protein mass (the portion of LPL largely associated with the vascular endothelium) by an actinomycin D-sensitive signalling mechanism (i.e. transcriptionally dependent process). Significant decreases of intracellular LPL protein content lagged behind the loss of HR-LPL protein. Treadmill walking raised LPL activity approximately 8-fold (P < 0.01) within 4 h after inactivity. The striking sensitivity of muscle LPL to inactivity and low-intensity contractile activity may provide one piece of the puzzle for why inactivity is a risk factor for metabolic diseases and why even non-vigorous activity provides marked protection against disorders involving poor lipid metabolism.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Time course for the decrease in muscle LPL activity after inactivity (hindlimb unloading, HU) compared with low-intensity ambulatory activity
Soleus HR-LPL activity was decreased after acute (1 day for 10 h, n = 3) or chronic (11 days of 10 h day−1, n = 8) HU (A). The time course of HR-LPL (B) and intracellular LPL (C) activities in soleus muscle within the first 18 h of HU revealed a delay of ≈4 h and then a precipitous decrease (n = 3–5). Restoring contractile activity for 4 h reversed the decrease in muscle LPL induced by 12 h inactivity. Control rats with normal cage activity (n = 5) and 12 h hindlimb unloaded rats (n = 20) were subjected to 4 h of intermittent treadmill walking (30 min intervals at 8 m min−1 four times separated by 30 min of ‘free in the cage’) and compared with rats with normal ambulatory activity or after 12 h HU. A direct comparison of the time course in the red oxidative slow twitch (soleus) and fast twitch (red quadriceps, RQ) muscles is shown (D). The half-life of LPL activity was calculated from 4 to 10 h using t1/2 = ln 2/k, where k = −1n (A(t)/A(0))/t. The average k calculated from 4 to 10 h was 0.334 for soleus and 0.341 for RQ. *P < 0.01 between HU and control.
Figure 2
Figure 2. LPL activity in different muscle fibre types after 12 h inactivity compared with low-intensity ambulatory activity
HR-LPL activity was determined in a slow twitch red (STR) soleus (n = 35), fast twitch red (FTR) deep quadriceps (n = 7) and fast twitch white (FTW) or superficial white region of rectus femoris (n = 6) and the diaphragm, which is a mixed skeletal muscle with continual activity (n = 7). *P < 0.01, †P < 0.05 between HU and low-intensity ambulatory control. LPL activity between all three hindlimb muscles was significantly different in controls but not after HU removed the normal contractile activity.
Figure 3
Figure 3. Inactivity decreases both muscle TG uptake and plasma HDL-C
The accumulation of TG-derived fatty acids in the RQ hindlimb muscles and heart (n = 3) was determined 10 min after injection of [3H]triolein-labelled chylomicron-like emulsion in rats following 18 h of HU and compared with rats with normal ambulatory activity (A). Rats with both 1 day (n = 6) and 11 days (n = 8) of intermittent (10–12 h HU day−1) inactivity had a significantly lower plasma HDL-C concentration compared with active controls (B). *P < 0.05 between HU and low-intensity ambulatory control.
Figure 4
Figure 4. Summary of the dose-response relationship between physical activity/inactivity and muscle LPL
Upper panel, summary of oxidative muscle sections (deep RQ and soleus); lower panel, summary of more glycolytic muscle sections (superficial white vastus lateralis and RF). Results for each muscle type are normalized to ambulatory control values. Absolute values for controls are shown in Fig. 2. Treadmill walking was at 8 m min−1. The data on the effects of low-intensity physical activity are from the current results, and those on high-intensity running (56 m min−1 3.5 h day−1) are from published work (Hamilton et al. 1998). The two studies used the same strain and vendor of rats.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Aldred HE, Perry IC, Hardman AE. The effect of a single bout of brisk walking on postprandial lipemia in normolipidemic young adults. Metabolism. 1994;43:836–841. - PubMed
    1. Alford EK, Roy RR, Hodgson JA, Ergerton VR. Electromyography of rat soleus, medial gastrocnemius, and tibialis anterior during hindlimb suspension. Exp Neur. 1987;96:635–649. - PubMed
    1. Augustus AS, Kako Y, Yagyu H, Goldberg IJ. Routes of FA delivery to cardiac muscle: modulation of lipoprotein lipolysis alters uptake of TG-derived FA. Am J Physiol. 2003;284:E331–339. - PubMed
    1. Bergo M, Wu G, Ruge T, Olivecrona T. Down-regulation of adipose tissue lipoprotein lipase during fasting requires that a gene, separate from the lipase gene, is switched on. J Biol Chem. 2002;277:11927–11932. - PubMed
    1. Bey L, Akunuri N, Hoffman PE, Zhao P, Hamilton DG, Hamilton MT. Patterns in global gene expression in rat skeletal muscle during unloading and low-intensity ambulatory activity. Physiol Genomics. 2003;13:157–167. - PubMed

Publication types

MeSH terms

LinkOut - more resources