Does it matter where fatty acids are oxidized, liver or skeletal muscle? Of course, they’re oxidized in both tissues (quantitatively much more in the latter), but relative increases in one or the other show interesting effects on appetite and the regulation of fat mass [in rodents].
Warning: a lot of speculation in this post.
A LOT.
It’s known that LC diets induce a spontaneous decline in appetite in obese insulin resistant patients. Precisely HOW this happens isn’t exactly known: the Taubes model? improved leptin signaling? probably a little bit of both, other mechanisms, and possibly this one:
Exhibit A. Oxfenicine
Oxfenicine blocks fatty acid oxidation in skeletal muscle in mice (Keung et al., 2013). This enhances muscle glucose uptake and oxidation, which reduces insulin. Fatty acid oxidation in liver increases. This also leads to reduced fat mass despite similar food intake, and it’s possible that liver fatty acid oxidation is a signal to the brain of well-fed status. When brain thinks the body is well-fed, energy expenditure is enhanced. In other words, it’s pharmaceutically mimicking some aspects of carb restriction (enhanced hepatic fat oxidation); this might also work with coconut oil
Exhibit B. Etomoxir
Etomoxir blocks liver fatty acid oxidation which makes brain think the body is starving: energy expenditure declines, fat mass goes up (Horn et al., 2004).
Exhibit C. C75
C75 enhances liver fatty acid oxidation (net effect similar to oxfenicine in this regard, but by a different mechanism): this increases energy expenditure and reduces fat mass despite similar food intake (Thupari et al., 2002 and 2004).
Summary
-Three different drugs, findings consistent with: enhanced liver fatty acid oxidation leading to increased energy expenditure and reduced fat mass (and vice versa)… the thing is, the effects on fat mass are secondary to changes in liver fatty acid oxidation. I think.
-Liver fatty acid oxidation: increased with coconut oil
-Insulin: decreases fatty acid oxidation and energy expenditure (in some contexts). This could explain, at least partially, why low carb diets & some of these drugs produce modest increases in energy expenditure (see above rodent-drug studies and study by Ebbeling).
[don’t take any of these drugs; that’s not the point of this post]
The fatty acid oxidation inhibitor & enhancer studies are exclusively rodent studies, but the metabolic effects are in agreement. This may also explain the subtle advantages of LC diets (in some #contexts). In other words, theoretically, maybe it’s not ketones per se (because I don’t think any of these critters were ketotic), but rather something related to the process of ketogenesis (ie, liver fatty acid oxidation), signaling the brain to regulate energy metabolism.
Just some thoughts. Maybe leptin is involved.
[or I could be totally wrong]
For full access to all articles and much more (or if you just like what I do and want to support it), become a Patron! Five bucks a month for full access and there are many other options. It’s ad-free and you can cancel if it sucks ????
Also, I’m open to suggestions so feel free to leave a comment or email me directly at drlagakos@gmail.com.
Affiliate discounts: if you’re still looking for a pair of hot blue blockers, Carbonshade is offering 15% off with the coupon code LAGAKOS and Spectra479 is offering 15% off HERE. TrueDark is running a pretty big sale HERE. If you have no idea what I’m talking about, read this then this.
20% off some delish stocks and broths from Kettle and Fire HERE.
If you want the benefits of ‘shrooms but don’t like eating them, Real Mushrooms makes great extracts. 10% off with coupon code LAGAKOS. I recommend Lion’s Mane for the brain and Reishi for everything else.