Tissue-specific fatty acid oxidation

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.


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.., as it is primarily oxidized in liver and there are some studies supporting this.



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).




-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 and low carb diets (ie, ketosis), and signals “well-fed status” to the brain which increases energy expenditure and reduces fat mass (by a little bit, but still…)

-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]

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