Lipotoxicity

Lipotoxicity: When tissues overeat

Recent findings

Excess lipid accumulation in non-adipose tissues may arise in the setting of high plasma free fatty acids or triglycerides.  Alternatively, lipid overload results from mismatch between free fatty acid import and utilization. Evidence from human studies and animal models suggests that lipid accumulation in the heart, skeletal muscle, pancreas, liver, and kidney play an important role in the pathogenesis of heart failure, obesity and diabetes.  Excess free fatty acids may impair normal cell signaling, causing cellular dysfunction. In some circumstances, excess free fatty acids induce apoptotic cell death.

Having stumbled across some disturbing information on elevated free fatty acids, I went back and dug up this review paper I had found a while back. 

IF the low carb gurus are correct -- and LC essentially makes MORE NEFA/FFA's available in circulation -- then I do worry about the long term benefits of LC. Fats in circulation can be as triglycerides or NEFA/FFA's but for some reason NEFA/FFA's aren't measured often (or at least paid attention to). In this regard, I don't want to be lulled into a false sense of security by low trigs.

Circulating NEFA/FFA's are to dietary fats what blood glucose, BG is to dietary carbs.  We have receptors to sense this nutrient level just as we have receptors to sense BG levels.  Elevated NEFA/FFA is as much a symptom of diabetes as are elevated BG levels -- perhaps moreso for Type 2's?

High plasma FFA and triglyceride levels lead to increased import of FFAs into non-adipose tissues, contributing to intracellular lipid accumulation.

As much as we all hate fat, adipocytes are where we're supposed to store fats.  I wonder sometimes if the reason I weigh so much more than I look like I do is because I'm storing fat in my muscle where perhaps it doesn't show up so much volume-wise.

Intracellular FFAs or their metabolites activate a serine/threonine kinase cascade that ultimately results in reduced insulin receptor substrate-1 tyrosine phosphorylation, reduced insulin receptor substrate-1-associated phosphatidylinositol 3-kinase activity and failure to promote translocation of the GLUT4 glucose transporter to the plasma membrane in response to insulin stimulation.

This gets all complicated, but basically this again demonstrates how elevated NEFA/FFA induces insulin resistance.  There are some in the LC community who hail this development.  The theory is IR is good because this directs glucose to the brain and our skeletal muscle is happy to thrive on ß-oxidation of fatty acids.  So the following questions to ponder arise:

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  What does this do for those who have a few carbs here and there ... as most of the LC community does (whether on plan or off) from time to time?
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  Is zero carb 24/7/365 dangerous or the only truly safe version of LC??
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  If LC manages one nutrient level that is elevated in T2 diabetics (BG), but exacerbates the other (NEFA/FFA), is it really a healthier dietary management strategy?