Wednesday, June 6, 2018

Thoughts on "Cardiolipin Synthesis in Brown and Beige Fat Mitochondria Is Essential for Systemic Energy Homeostasis"

Interesting confirmation of a core mitochondrial functional role for cardiolipin, and some interesting observations about cold-adaptation.

Get used to shivering! 
"However, the ability of adipose tissue to expend energy is a dynamic process that continues to increase with prolonged cold exposure, only reaching maximal capacity after several weeks (Cannon and Nedergaard, 2004)."
And clearly staying warm is overwhelmingly dependent on fat metabolism.
"However, the enrichment of lipid metabolism proteins far eclipsed that of proteins involved in all other metabolite pathways from 3 days to 3 weeks of cold exposure (Figure 1B)."
This likely explains why overweight people or inactive people have such a problem staying warm. Fat-burning capacity is dependent on stimulus, and while this doesn't show it, it likely atrophies like every other function of the body. Use it or lose it.

One of the key questions around cardiolipin and omega-6 fat intake is: what is a cardiolipin supposed to look like? This is more evidence that they're not supposed to be saturated with linoleic acid, leaving them uniquely susceptible to oxidizing and producing toxins like HNE as they damage mitocondrial function.
"Newly synthesized CL is characterized by shorter, more saturated acyl chains, which can be remodeled by phospholipases, and acyltransferases through monolysocardiolipin (monolysoCL) intermediates to generate a diverse pool of CLs."
It shouldn't surprise that CL is produced in an ideal state. Why it so readily takes up linoleic acid is an interesting question...

The paper also claims that energy production in brown-fat adipocytes (fat cells) controls systemic glucose homeostasis and therefore type 2 diabetes.

I'm a little more skeptical of that claim, as I looked into the connection between mitochondrial dysfunction and diabetes, and it's not as clear as I would like it to be. If this was a clear mechanism, then it would suggest that people living in warm climates that never experience a need for cold thermogenesis would be more susceptible to diabetes, and we really don't see that.

They get it when the industrial diet is introduced, same as everyone else on the planet.