Palmitic acid and hyperglycaemia in diabetic heart failure (1)

I've been gifted a paper of great interest. The authors of the paper are very good in their explicit discussions of the limitations of their models, the reasons for the choices they made and the limitations of all current models and probes. This is good and, needless to say, there are an awful lot of "ifs, buts and maybes" to the data! On the down side the paper is an epub of the crudest type, retaining numbered lines, the figures at the very end of the whole paper and all of the captions in a lump between the references and the figures. So not easy reading for a very complex paper, with very complex figures and very complex captions. I spent a large amount of time on this paper over the Christmas vacation but never hit post on any of it. Here is an introduction.

Over the years we have seen, largely via Veech, the ability of ketone bodies alone to rescue myocardial function to give mechanical work performance comparable to the combination of insulin with a relatively normal level of glucose in the perfusion of isolated rat hearts. Equally there is the concept that ketones essentially bypass insulin resistance to rescue metabolism.

The hearts in Veech's study were perfused with oxygenated buffer which was devoid of the free fatty acids which are a normal metabolic substrate for heart muscle.

As a lipophile I have long wondered whether, outside of the neurons, palmitic acid might be a reasonable substitute for ketones in rescuing muscle metabolism damaged by hyperglycaemia.

From the start of the discussion section of Bhatt's paper:

"We investigated the role of substrate-driven redox status on the contractile/energetic performance of heart trabeculae from the T2DM ZDF rat. The main findings are: i) HG exerts a detrimental action on contractility of T2DM heart trabeculae that Palm is able to rescue; ii) Palm prevents oxidative stress exacerbated by HG, an effect independent from insulin action; iii) insulin appears to worsen the negative effect of HG through higher oxidative stress and lower GSH; iv) ZDF heart mitochondria emit less ROS and display higher ROS scavenging capacity of the GSH/Trx antioxidant systems; v) cardiac redox balance in HG appears to play a causal rather than correlative role in the preservation of contractile performance in ZDF trabeculae"

Palmitic acid will rescue hyperglycaemia induced myocardial contractility failure. OK, I'm happy.

This was the core finding in the paper. There are a whole slew of spin off concepts which grow from it but if I wait until I have them all sorted out it might be a very long time before I get another post out!

But here we have it. Hyperglycaemia is bad. Palmitic acid rescues hyperglycaemia induced dysfunction. A paradigm shift in glucose vs FFAs!

Peter