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Background: Many of the metabolic effects of exercise are due to the most recent exercise session. With recent advances in nuclear magnetic resonance spectroscopy (NMRS), it is possible to gain insight about which lipoprotein particles are responsible for mediating exercise effects., Methods: Using a randomized cross-over design, very low density lipoprotein (VLDL) responses were evaluated in eight men on the morning after i) an inactive control trial (CON), ii) exercising vigorously on the prior evening for 100 min followed by fasting overnight to maintain an energy and carbohydrate deficit (EX-DEF), and iii) after the same exercise session followed by carbohydrate intake to restore muscle glycogen and carbohydrate balance (EX-BAL)., Results: The intermediate, low and high density lipoprotein particle concentrations did not differ between trials. Fasting triglyceride (TG) determined biochemically, and mean VLDL size were lower in EX-DEF but not in EX-BAL compared to CON, primarily due to a reduction in VLDL-TG in the 70-120 nm (large) particle range. In contrast, VLDL-TG was lower in both EX-DEF and EX-BAL compared to CON in the 43-55 nm (medium) particle range. VLDL-TG in smaller particles (29-43 nm) was unaffected by exercise. Because the majority of VLDL particles were in this smallest size range and resistant to change, total VLDL particle concentration was not different between any of these conditions. Skeletal muscle lipoprotein lipase (LPL) activity was also not different across these 3 trials. However, in CON only, the inter-individual differences in LPL activity were inversely correlated with fasting TG, VLDL-TG, total, large and small VLDL particle concentration and VLDL size, indicating a regulatory role for LPL in the non-exercised state., Conclusions: These findings reveal a high level of differential regulation between different sized triglyceride-rich lipoproteins following exercise and feeding, in the absence of changes in LPL activity.

Physical inactivity is a risk factor for lipoprotein disorders and the metabolic syndrome. Physical inactivity has a powerful effect on suppressing lipoprotein lipase (LPL) activity in skeletal muscle, the rate-limiting enzyme for hydrolysis of triglyceride (TG)-rich lipoproteins. We tested the ability of several compounds to prevent the decrease in LPL. The present study minimized standing and ordinary light nonexercise movements in rats to compare the effects of inactivity and nonexercise activity thermogenesis (NEAT) on LPL activity. The key new insight was that the typically quick decrease in LPL activity of oxidative muscle caused by physical inactivity was prevented by nicotinic acid (NA), whereas inhibitors of TNF-alpha, inducible nitric oxide synthase, and NF-kappaB had no such effect. NA was administered at a dose known to acutely impede the appearance of plasma TG from the liver and free fatty acids from adipose tissue, and it was effective at intentionally lowering plasma lipid concentrations to the same level in active and inactive groups. As measured from heparin-releasable LPL activity, LPL in the microvasculature of the most oxidative muscles was approximately 90% lower in the inactive group compared with controls, and this suppression was completely blocked by NA. In contrast to inactivity, NA did not raise muscle LPL in ambulatory controls, whereas a large exogenous fat delivery did decrease LPL activity. In vitro control studies revealed that NA did not have a direct effect on skeletal muscle LPL activity. In conclusion, physical inactivity amplifies the ability of plasma lipids to suppress muscle LPL activity. The light ambulatory contractions responsible for NEAT are sufficient for mitigating these deleterious effects.

Some health-related proteins such as lipoprotein lipase may be regulated by qualitatively different processes over the physical activity continuum, sometimes with very high sensitivity to inactivity. The most powerful process known to regulate lipoprotein lipase protein and activity in muscle capillaries may be initiated by inhibitory signals during physical inactivity, independent of changes in lipoprotein lipase messenger RNA.

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.

Atorvastatin is a drug of choice in the treatment of coronary heart disease, because this hepatic 3-hydroxy-3-methylglutaryl coenzyme reductase inhibitor significantly decreases plasma cholesterol and triglyceride levels. However, little is known about the underlying molecular targets of this drug. Lipoprotein lipase (LPL), an enzyme with multiple functions in non-hepatic lipid metabolism, may be a potential candidate and LPL gene expression may increase in response to a treatment with atorvastatin. In order to verify this hypothesis, mouse 3T3-L1 preadipocytes were incubated with 1 and 10 micromol/l atorvastatin for 24 and 48 h and LPL mRNA concentration was measured by reverse transcription-polymerase chain reaction. Our data indicated that atorvastatin increased LPL mRNA concentration by a time- and dose-dependent mechanism. LPL mRNA concentration was significantly increased by 82% with 10 micromol/l atorvastatin after 48 h. LPL mRNA concentration was 28% greater (not significant) than control with 10 micromol/l atorvastatin after 24 h. No increase was obtained with 1 micromol/l atorvastatin after 24 or 48 h. The first 976 nucleotides of rat LPL promoter were transfected in 3T3-L1 preadipocytes. Addition of 10 micromol/l atorvastatin for 48 h resulted in a 44% increase of rat LPL promoter activity. This study demonstrates for the first time that a statin can regulate LPL gene expression transcriptionally in preadipocytes., (Copyright 2002 S. Karger AG, Basel)

Presents information on a study which determined the role of local contractile activity on lipoprotein lipase (LPL) regulation in different muscle fiber types. Materials and methods; Heparin-resealable LPL enzyme activity; LPL protein mass in sedentary control and voluntary run trained muscles.