marți, 10 martie 2009

for the low carb fanatics - de pe un forum

Like most low carb fanatics who are ignorant of all but the most pop-physiology, you’re incorrect to think that fat balance is all about insulin.

You need to understand that there are a multitude of enzymes that are involved in triacylglycerol synthesis and lipolysis. “Insulin” is not a pathway. It’s one of several hormones that have an effect on the enzymes that comprise the actual pathways. What enzymes am I talking about? For fatty acid uptake, there’s FAT/CD36, FATP-1 to -6, and FABPpm. For fatty acid synthesis, there’s fatty acid synthase. For glucose uptake, there’s Glut1 and Glut4. For esterfication, there’s GPAT, PAP1, and DGAT1 and DGAT2. For lipolysis, there’s HSL, perilipin, and Protein kinase A.

What “regulates all this?” It’s definitely not just “insulin”. That’s an incredibly simplistic, insulinocentric view. You know what else has an effect on these lipogenic/lipolytic enzymes besides insulin? There’s angiotensin II, the adrenergic receptor (catacholamines), FoxC2, PTP1B, and last but not least ASP.

ASP stimulates triacylglycerol synthesis more than any other known adipose tissue factor. It’s also a potent stimulator of glucose transport [PMID: 9130021]. It works independently of insulin, through a different signaling pathway. It effectively synthesizes triacylglycerol even in the absence of glucose and insulin [PMID: 8492712]. Finally, guess what the primary regulator of ASP production is? Dietary fat (packaged as chylomicrons) [PMID: 9694837]. Fat intake and ASP will lead to a positive fat balance just as much as carb intake and insulin will. Which is why it’s all about calories. Unfortunately, low carb nuts never look past insulin. They ignore (or are ignorant of) the fact that fat stores itself with tremendous efficiency without any insulin whatsoever.

Take a look at the broader picture. Fatty acids are taken up into adipocytes via facilitated diffusion, mediated by fatty acid transporters like the ones I mentioned above. You don’t need insulin for this. Dietary FFAs will diffuse into adipocytes down the concentration gradient. There may even be passive diffusion. You then need a triacylglycerol backbone and the acylation (esterfication) steps that lead to the production of a triacylglycerol. ASP can stimulate both. After all, it’s called “acylation-stimulating protein.” This process works just fine with basal levels of insulin or glucose. And as explained before, ASP is produced in response to FAT INTAKE.

Weight loss is all about negative calorie balance, not lowering of insulin. Research clearly shows that when isonitrogenous diets are compared, higher carb diets (with higher insulin levels) do JUST AS WELL as lower carb diets at reducing bodyfat. While low carb diets have lower insulin levels, they have higher ASP levels. And vice versa with a low fat diet. Why? Because carb intake (or type) and insulin levels are absolutely unable to account for fat loss. It’s all about energy balance.

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