Nelson asserts that cardio is simply more burned calories.
Observe:
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Biochem. Soc. Trans. (2001) 29, (774–777) (Printed in Great Britain)
Uncoupling protein 3 biological activity
J. P. Giacobino1
Département de Biochimie Médicale, Centre Médical Universitaire, CH-1211 Genève 4, Switzerland
The hypothesis that uncoupling protein 3 (UCP3) is an uncoupling protein involved in heat dissipation is not unequivocally supported. An update of in vitro, ex vivo and in vivo studies testing this hypothesis is presented. Data are provided showing that exercise induces a fatty acid-dependent increase in muscle UCP3 mRNA in humans. The proposed positive correlation between glycolytic capacity and UCP3 level in various muscle-fibre types in the mouse is reassessed. Finally, an association between an intronic polymorphism of UCP3 and adiposity is reported.
In 1997, i.e. 21 years after the first report on uncoupling protein (UCP) 1, two novel members of the mitochondrial carrier family were discovered which displayed high ( 55%) amino acid sequence identity to UCP1. Based on these identities the two novel proteins were considered as possible UCPs and named UCP2 and UCP3 [1,2]. They were found to be highly expressed not only in rodents but also in humans; UCP2 in most tissues studied [1] and UCP3 mainly in skeletal muscle [2]. Since the discovery of UCP2 and UCP3 many experimental approaches have been developed to test the hypothesis that these proteins might be uncouplers of oxidative phosphorylation and, therefore, participate in heat dissipation. In this presentation we will focus on UCP3.
…and then later…
An intriguing aspect of the biological role of UCP3 is its possible interaction with glucose uptake. A relationship between UCP3 expression and glucose uptake has been suggested in both rodents and humans. Indeed, in transgenic mice overexpressing UCP3 in their skeletal muscle, an increased insulin sensitivity was observed [12]. Furthermore, in L6 myotubes, UCP3 transfection was found to increase glucose transport. This phenomenon was mediated by activation of the phosphoinositide 3-kinase-dependent pathway [16]. Moreover, overexpression of GLUT4 in mice caused an up-regulation of UCP3 in skeletal muscle [17]. In humans, the level of UCP3 mRNA in skeletal muscle of type II diabetic patients was lower than in control subjects [18]. There was also a positive correlation between UCP3 expression and whole-body insulin-mediated glucose utilization among diabetic patients [18]. These results suggest that glucose utilization or, in general, an overflow of substrate positively modulates UCP3 expression. They also suggest the opposite hypothesis, i.e. that UCP3 improves insulin sensitivity. If this were true then stimulation of UCP3 activity might help to correct insulin resistance.
A model of physical exercise in humans was used to investigate the effect of free fatty acids (FFA) and/or glucose oxidation on UCP3 mRNA level. This study was performed in collaboration with Dr P. Schrauwen's group in the Department of Human Biology, Maastricht University, Maastricht, The Netherlands. Seven healthy untrained men exercised at 50% O2max for 2 h and then rested for 4 h. Skeletal-muscle biopsies and blood samples were taken before and 0, 1 and 4 h after exercise. To modulate plasma FFA levels, the experiment was performed twice, once after a fasting period and once with glucose ingestion. UCP3 mRNA was determined by competitive reverse transcriptase PCR. In the fasted state, plasma FFA levels increased during exercise whereas they were unchanged after glucose ingestion. Also, fat oxidation was higher after fasting. In the fasted state UCP3 mRNA expression was increased 4 h after exercise. This increase was prevented by glucose ingestion. In conclusion, our data suggest that the up-regulation of UCP3 mRNA following exercise is not a direct effect of exercise, but rather an effect of increased FFA availability/oxidation and that during exercise there is no correlation in skeletal muscle between glucose utilization and UCP3 expression.
So the exercise causes...what? AN INCREASE IN FFA OXIDATION, and what is the UCP3 expression correlation to glucose utilization? NONE. It is a separate mechanism altogether. What could it be? Let's look...
UCP3 protein and fasting
Fasting was repeatedly shown to increase dramatically muscle UCP3 mRNA in rats and mice [4–6]. Two studies reported that the increase in rat UCP3 protein induced by fasting was less than half the increase of UCP3 mRNA in experiments carried out in parallel [15,20]. Our data confirmed these results which altogether indicated that, in fasting, the amplitude of UCP3 changes at the mRNA level are strongly damped down when the amount of protein is considered. This suggests a regulation of UCP3 expression at the translational level.
The phenomenon of the increase in UCP3 expression during fasting, called 'the fasting paradox', is therefore still observed, although at a lower level, when UCP3 protein instead of mRNA is measured.
The fasting paradox, it's called...I am looking into it. See that good evidence that the body actually specifically accelerates fatloss in a fasted state? Sure, other factors impact the degree, and I am perusing other studies to find those factors and to what degree they impact things.
UCP3 genetic studies
Up to now, the results of UCP3 genetic studies are rather controversial and only weak associations have been described between some UCP3 variants and obesity traits.
We have analysed, among 734 subjects from the Québec Family Study (QFS), a new GA repeat microsatellite located in UCP3 gene intervening sequence 6 (GAIVS6). Covariance analysis across genotypes for different adiposity, resting energy expenditure and glucose metabolism variables was undertaken with age and sex, plus body fat and body mass for non-adiposity phenotypes, as covariates. We found strong associations between GAIVS6 and body-mass index, percentage of body fat, the sum of six skin-fold thickness and leptin level. Homozygotes for the GAIVS6 240 bp alleles (15% frequency in the QFS) showed higher adiposity than subjects with the GAIVS6 238 bp allele (70% in QFS). These results suggest that some alleles of UCP3 might contribute to the aetiology of human obesity.
Altogether, the data presented support the view that UCP3 is thermogenic but the idea that it might be thermoregulatory is still controversial.
References
1 Boss, O., Samec, S., Paoloni-Giacobino, A., Rossier, C., Dulloo, A., Seydoux, J., Muzzin, P. and Giacobino, J. P. (1997) FEBS Lett. 408, 39–42
Medline 1st Citation 2nd
2 Fleury, C., Neverova, M., Collins, S., Raimbault, S., Champigny, O., Levi-Meyrueis, C., Bouillaud, F., Seldin, M. F., Surwit, R. S., Ricquier, D. and Warden, C. H. (1997) Nat. Genet. 15, 269–272
Medline 1st Citation 2nd
This study not only references, factually, the enhanced fatburning aspect of exercise after fasting, but also addresses the issue that I had brought up concerning some sort of mechanism by which fat was actually burned specifically with preference, while muscle was specifically preserved.
Also, consider the impact that exercise has on mitochondria…how do the mitochondria replicate themselves? When they get too large, they divide, that’s how. What would an enhanced mitochondria population result in?
THINK about that.
Exercise impacts these things other than calories:
VO2 max
a-v O2 difference
Mitochondria
Heart rate, both resting and during exercise
Blood Pressure
Metabolism
Cardio is NOT simply the expenditure of calories. Not by a long shot.
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Oh that's right... and the timing of your meals and macronutritional ratios doesn't matter either.
