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Randomised crossover PubMed records 3 February 2004 as the publication date. The print issue is volume 287, issue 1, dated July 2004. Cite the February 2004 date.

In forty eight hours, the carbohydrate genes and the fat genes moved in opposite directions

AI narration, generated on first listen
Journal
American Journal of Physiology, Endocrinology and Metabolism 287(1):E25 to E31
Authors
Arkinstall MJ, Tunstall RJ, Cameron-Smith D, Hawley JA
Institution
RMIT University
Published
3 February 2004
Source
PMID 14761878 · DOI 10.1152/ajpendo.00557.2003
Design
Randomised crossover comparing two isoenergetic diets for forty eight hours following an exhausting glycogen depleting exercise bout. The low carbohydrate arm provided 0.7 grams of carbohydrate per kilogram of body mass, the high carbohydrate arm 10 grams per kilogram. Resting muscle was analysed for the messenger RNA of GLUT4, glycogenin, PDK4, FAT/CD36, carnitine palmitoyltransferase I, hormone sensitive lipase, beta hydroxyacyl CoA dehydrogenase and uncoupling protein 3. Blood was sampled for glucose, insulin and free fatty acids.
Sample
Seven men.

What PDK4 is

Carbohydrate has to pass through one gate to be burned aerobically, an enzyme complex called pyruvate dehydrogenase. PDK4 is the enzyme that shuts that gate, so the amount of PDK4 is the clearest single readout of whether a muscle is currently set up to spare carbohydrate or to spend it.

Drawn from background physiology, not from this paper.

Why they ran it

Changing the macronutrients in a diet alters the substrate available in muscle and blood, and that was known to matter for gene expression, but very few studies had examined what diet manipulation actually does to gene expression in human skeletal muscle. The authors set out to quantify it for a selected set of carbohydrate related and fat related genes.

Drawn from the paper's stated aim.

Seven men performed an exhausting exercise bout to deplete muscle glycogen, then ate for forty eight hours either a low carbohydrate diet at 0.7 grams per kilogram of body mass, or a high carbohydrate diet at 10 grams per kilogram. Resting muscle and blood were then sampled.

The two arms ended in very different states. Muscle glycogen was about 300 percent higher after the high carbohydrate condition, at P less than 0.001. Free fatty acid concentrations were twofold higher after the low carbohydrate condition, at P less than 0.05.

On the carbohydrate side, the high carbohydrate arm raised the messenger RNA for GLUT4, the glucose transporter, and for glycogenin, and lowered the messenger RNA for PDK4, the brake on carbohydrate oxidation. All at P less than 0.05.

On the fat side, the low carbohydrate arm raised the messenger RNA for FAT/CD36 at P less than 0.05 and for uncoupling protein 3 at P less than 0.01. The authors describe the whole pattern as a coordinated change rather than a set of separate ones.

The numbers

Low carbohydrate arm0.7 g/kg body mass carbohydrate, 48 hours
High carbohydrate arm10 g/kg body mass carbohydrate, 48 hours
Muscle glycogen, high versus low carbohydrateabout 300 percent higher, P less than 0.001
Plasma free fatty acids, low versus high carbohydratetwofold higher, P less than 0.05
GLUT4 and glycogenin messenger RNAincreased after high carbohydrate, P less than 0.05
PDK4 messenger RNAreduced after high carbohydrate, P less than 0.05
FAT/CD36 messenger RNAincreased after low carbohydrate, P less than 0.05
Uncoupling protein 3 messenger RNAincreased after low carbohydrate, P less than 0.01

Why this might happen

Shown in this study The study measured this step directly.

Their conclusion is that a short term exercise and diet intervention has a rapid capacity to produce coordinated changes in the transcription of metabolically related genes.

The word doing the work there is coordinated. This is not two dials being turned by two different hands. The authors read the pattern as one regulatory response rather than a set of separate ones, which is what makes it a switch.

Drawn from the paper's stated conclusions.

What this does not show

  • It does not show a reciprocal switch in the muscle's actual behaviour. Everything measured here is messenger RNA in resting muscle. Transcript abundance is a statement of intent, not of capacity and not of flux. No protein, no enzyme activity and no substrate use during exercise were measured.
  • The two arms differ in far more than dietary carbohydrate. Muscle glycogen differed roughly fourfold and plasma free fatty acids twofold. Insulin and glucose moved too. The design cannot say which of those signals the genes were responding to, only that the whole package moved together.
  • Everyone did the depleting exercise first. This is diet layered on top of glycogen depleting exercise, not diet on its own. A well fed person who has not just exercised to exhaustion is a different starting point.
  • Seven men. A small single sex sample, and the paper reports transcripts at one time point after forty eight hours, so nothing here describes how the pattern develops or how long it lasts.

Where this leaves us

The reciprocal shape of the response is now on the record in human muscle and inside two days. Raising carbohydrate raised the transporter for glucose and released the transcriptional brake on burning it, while lowering carbohydrate raised the fat transporter instead. This refines the earlier fat diet work by showing the mirror image of it in the same tissue.

Seven men, sampled at rest, forty eight hours after an exhausting glycogen depleting exercise bout.

The same crossover carried through to protein abundance, enzyme activity and measured substrate use during exercise, which would show whether the transcript switch becomes a functional one.

Caveats worth holding

  • Messenger RNA only. No protein abundance, no enzyme activity and no measurement of substrate use during exercise.
  • The abstract reports direction and P values for the transcripts but not the fold changes, so the size of each transcript response cannot be stated here.
  • Both arms performed the same exhausting depletion bout beforehand, so the comparison is between diets on top of depletion.
  • The full discussion was not openly reachable, so the mechanism section rests on the paper's stated conclusions.
  • Seven men, one time point, no women.

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