The regulation of adipose tissue and muscle lipoprotein lipase in runners by detraining.

Abstract

IntroductionTo study the mechanism of lipoprotein lipase (LPL) regulation by exercise, we recruited 16 healthy athletes to undergo a 2-wk period of detraining. Fasting fat and muscle biopsies were performed both before and after the detraining period. In muscle, detraining resulted in a decrease in LPL activity in both the heparin-releasable (HR) (-45%, P < 0.05) and cellular (ex- Triglyceride-derived FFA are taken up by tissues through the action oflipoprotein lipase (LPL)'(1), which is found predominantly in adipose tissue and muscle. In human adipose tissue, little FFA is synthesized from glucose, and therefore LPL is an important enzyme for lipid storage (2). In contrast, muscle uses FFA for oxidation (3). The LPL found in both adipose tissue and muscle contributes to the clearance of circulating triglyceride-rich lipoproteins.Previous studies have examined the effects of exercise on LPL activity, using a number of different exercise regimens (reviewed in reference 4). Studies of endurance training in human subjects showed significant increases in LPL activity, both in skeletal muscle and adipose tissue, as well as in postheparin plasma. Weight loss also yields increases in adipose LPL (5), however, and many studies of exercise did not control for weight loss during the exercise regimen. Kiens et al. (6) studied six healthy men in which LPL activity was measured in the knee extensors at rest and after 8 wk of training of one leg, while the other leg was not exercised and served as a control. They found a 70% increase in LPL activity in the trained leg compared with the nontrained one.A number of previous studies have examined the mechanism of LPL regulation, and have discovered that LPL may be regulated at multiple different cellular sites (7). This study was designed to examine the mechanism of regulation of LPL by exercise in adipose tissue and muscle. As described below, short-term changes in exercise altered LPL activity in both tissues through posttranslational changes. Methods Recruitment ofstudy subjects. 16 subjects (10 men and 6 women; age, 37±2 yr) were recruited for this study, and their characteristics are shown in Table I. All subjects were in good health, were taking no medications, and were running 2 32 km/wk, or performing an equivalent amount of aerobic exercise (one subject bicycled -600 km/ week). 6 of the 16 subjects ran a marathon within 1 mo preceding the study. To participate in the study, the subjects had to agree to detrain for 2 wk, and gave informed consent to the procedures. Detraining entailed no aerobic exercise, but just activities of daily living. Compliance with these instructions was judged to be excellent. This protocol was approved by the Internal Review Board of Cedars-Sinai Medical Center, and subjects gave informed consent to the procedures.

Physical activity, obesity and blood lipids

“…They reported data for endurance athletes in the trained state and after two-weeks of detraining; LPL activity in muscle decreased markedly with detraining, alongside a clear increase in the activity of this enzyme in adipose tissue. 77 These ®ndings, and a recent report of an association between low skeletal muscle LPL activity and increased systemic respiratory quotient (hence reduced fat oxidation), 78 demonstrate the potential of exercise with the body's large muscles to in¯uence body composition in the longterm. This may be most dramatically demonstrated by comparison of responses to a high fat diet in mice; the profound increase in fat mass induced in normal animals by this diet was largely avoided in transgenic mice which over-expressed skeletal muscle LPL.…”

Effect of 2-month detraining on body composition and insulin sensitivity in young female dancers

“…23,24 Previous studies have shown that greater physical activity can lead to greater storage of glycogen 2 and triglycerides 25 in the recruited skeletal muscle. Conversely, Simsolo et al 26 demonstrated that the decreased physical activity generates a condition favoring triglyceride partitioning to adipose tissue storage in contrast to skeletal muscle. Therefore, reduction in fuel uptake of skeletal muscle and increase in fat uptake of adipose tissue by detraining could account for the presently observed increase in waist circumference without showing an increase in body mass in these young female dancers.…”

Transgenic Mice Expressing Lipoprotein Lipase in Adipose Tissue

“…Ethidium bromide signal densities were integrated using Eagle Eye software. Values from varying cycle numbers (15,17,20,25,30,35,40, and 45 cycles) were obtained. Products were normalized for size with markers of known DNA quantities (GeneChoice DNA Ladder I, PGC Scientifics), and normalized densities were plotted with PCR cycle number to establish linearity.…”

“…PCR was performed at different cycle numbers to ensure linearity of the product. This gel is representative and shows 15,17,20,25,30, and 35 cycles of PCR, lanes 1-6 respectively, for each group. B, integrated densities of quantitative PCR products were normalized to markers of known quantities of DNA and values were plotted.…”

“…The enzyme is synthesized and secreted by adipocytes and muscle cells, and transported to the capillary endothelium, where hydrolysis of the triglyceride core of circulating VLDL and chylomicrons takes place. Although the changes in LPL activity with different physiologic states have been well described (1), the mechanism of LPL regulation is complex and occurs at levels of transcription (2)(3)(4)(5)(6), translation (7)(8)(9)(10)(11), and post-translational processing (12)(13)(14)(15) in response to both cell type and regulatory factors. Previous studies have demonstrated translational regulation of LPL.…”