RWhigham wrote: i'm going to take time to answer the sweeping statements with no references (except himself and he is an authority) in the preceding post from Michael, our resident SENS and CRAN expert.
I'm not sure how you missed them, but I cited these two papers.
This isn't actually how this works. The size, composition of lipid droplets doesn't simply reflect dietary intake; and saturated and unsaturated fats both promote lipophagy.
Differential roles of unsaturated and saturated fatty acids on autophagy and apoptosis in hepatocytes
The unsaturated fatty acid, oleic acid, promoted the formation of triglyceride-enriched lipid droplets. In contrast, the saturated fatty acid, palmitic acid, was poorly converted into triglyceride-enriched lipid droplets
Ahem. First, your quote from me is a bit truncated, and your summary of the "Differential roles" abstract is missing some key elements. What I said in full was,
Michael wrote: The formation, size, and persistence of lipid droplets is regulated by a variety of things, of which fat intake is a very minor one [...]
The composition of lipid droplets doesn't simply reflect dietary intake; and saturated and unsaturated fats both promote lipophagy at the regulatory level, beyond their presence in lipid droplets, via different mechanisms: in general, unsaturated fatty acids stimulate autophagy and protect against apoptosis, whereas saturated FA inhibit it and promote apoptosis (but there are poorly-understood exceptions).
And what the "Differential roles" paper says is,
The unsaturated fatty acid, oleic acid, promoted the formation of triglyceride-enriched lipid droplets and induced autophagy but had a minimal effect on apoptosis. In contrast, the saturated fatty acid, palmitic acid, was poorly converted into triglyceride-enriched lipid droplets, suppressed autophagy, and significantly induced apoptosis. Subsequent studies revealed that palmitic acid-induced apoptosis suppressed autophagy by inducing caspase-dependent Beclin 1 cleavage, indicating cross-talk between apoptosis and autophagy. Moreover, our data suggest that the formation of triglyceride-enriched lipid droplets and induction of autophagy are protective mechanisms against fatty acid-induced lipotoxicity.
So, we see here that "The formation and composition of lipid droplets doesn't simply reflect dietary intake:" part of the reason why you see more PUFA in LD is because saturated fatty acids are resistant to incorporation, even when present. And, on the flip side, PUFA induce autophagy even as they form LD, facilitating LD clearance after initial sequestration in LD, whereas palmitic acid fails to do so under these circumstances (with the result of lipotoxic apoptosis).
Here is another paper reflecting this general schema:
Oleic acid supplementation leads to triglyceride accumulation and is well tolerated, whereas excess palmitic acid is poorly incorporated into triglyceride and causes apoptosis. Unsaturated fatty acids rescue palmitate-induced apoptosis by channeling palmitate into triglyceride pools and away from pathways leading to apoptosis. Moreover, in the setting of impaired triglyceride synthesis, oleate induces lipotoxicity. Our findings support a model of cellular lipid metabolism in which unsaturated fatty acids serve a protective function against lipotoxicity though promotion of triglyceride accumulation.
However, as I noted, there are exceptions: under some conditions, SaFA also promote autophagy via an AMPK-, PKR-, and JNK1-dependent process.
RWhigham wrote:
The role of lipid droplet formation in the protection of unsaturated fatty acids against palmitic acid induced lipotoxicity to rat insulin-producing cells
Long-chain unsaturated NEFAs strongly induce the formation of lipid droplets ... On the other hand the saturated NEFA palmitic acid only induced minor lipid droplet formation ...
Take away: LD's form from unsaturated fatty acids
So, again we see that even when present, palmitic acid as a representative SaFA are resistant to LD formation, meaning that "The composition of lipid droplets doesn't simply reflect dietary intake."
And what happens when you look at the interaction of different FA in this process?
PA [palmitic acid] induced cell death in a dose dependent manner up to 1.5 mM, but AA [arachidonic acid] protected substantially lipotoxicity caused by PA at even low concentration of 62 μM, at which monounsaturated fatty acids including palmitoleic acid (POA) and oleic acid (OA) did not protect as much as AA did. ...
Based on the observations that polyunsaturated AA generated competently cellular droplets at low concentration within the cytosol of myotubes compared with monounsaturated fatty acids, and AA-driven lipid droplets were also enhanced in the presence of PA, we hypothesized that incorporation of harmful PA into inert triglyceride (TG) may be responsible for the protective effects of AA against PA-induced lipotoxicity. To address this assumption, C2C12 myotubes were incubated with fluorescent probed-PA [...] in the presence of AA and their subsequent lipid profiles were analyzed. The analyses of lipids on thin layer chromatograpy (TLC) showed that fluorescent PA analogue was rapidly channeled into AA-driven TG droplets.
Lipid Droplets in Health and Disease
LD biogenesis is stimulated upon an increase in intracellular free FA levels.
Uptake of individual fatty acids into adipose tissue in relation to their presence in the diet
Shows that adipose cells store dietary fats in the preferential order: monounsaturated, n-6 polyunsaturated, saturated. So with what most people eat, the FA's stored and then released by adipose cells are mostly not saturated and will stimulate LD biogenesis--directly related to a diet high in unsaturated fats.
Take away: Dietary unsaturated fats increase LD's
Actual takeaway: even for storage in adiopose tissue, there is a preferential order — that is, a regulated order, independent of dietary intake — in which cells store fatty acids into LD. "In relation to the amount fed, storage of fatty acids differed (P < 0.01) between classes (n−3 polyunsaturated < saturated < n−6 polyunsaturated < monounsaturated); oleic acid was stored in the greatest amounts." Because adipocytes are primarily a storage organ, the preferential order in adiopocytes mostly reflects the differential incorporation of different FA into chylomycrons: in other cell types, as documented above (and below), there is a greater degree of selective incorporation within the cell itself.
RWhigham wrote: The single large "LD" in an adipose cell is in a constant state of simultaneously storing and removing (via lipolysis) fatty acids and glycerol molecules from the LD. There is no lipophagy there. The adipose LD is much too large. On the other hand, non-adipose cells make relatively small LD's. They appear to change size through fission and fusion much like mitochondria, and the smaller ones are easily degraded.
Autophagy certainly regulates lipid droplet dynamics differently in adipocytes than other tissues. "Adipocytes represent the primary cell type of adipose tissue and are responsible for storing excess calories as triglycerides in their cellular lipid droplets without the common lipotoxicity experienced by other cells under these conditions (Konige et al., 2014). This unparalleled capacity for lipid storage and release upon systemic metabolic demand links the cell biology of the adipocyte and adipose tissue physiology to whole body metabolism (Fig. 1)."[source]
RWhigham wrote: In conclusion
- LD's contain mostly unsaturated fats that were at some point consumed
- When LD's are not removed, they grow in number and size and result in disease.
- LD removal must be preceded by autophagy
- In the early stages of autophagy LD's grow in size, so it likely takes awhile before lipophagy kicks in
- It appears to be lipophagy, not LP lipolysis, that is enabled by autophagy
I agree with all of that; I'm not sure why you were adding that additional information (and documentation, which I snipped), which doesn't relate to my response to which you seem to have taken umbrage.