Part 7 - An Energy Delivery Model: Efficient Triglyceride Uptake and An Increased Energy Demand
Previous - Part 6 - An Energy Delivery Model: The Consequences of Poor Triglyceride Utilization
In the previous section, we discussed the causes and consequences of poor triglyceride utilization by the cells of the body, and the way in which this can lead to elevated LDL cholesterol. In this case, it was poor uptake of triglycerides and subsequent return of excess triglycerides to the liver that led to a compensatory increase in VLDL production. These excess cholesterol-containing VLDL particles inevitably convert to LDL, leading to an increase in measured LDL cholesterol.
This is, however, not the only way by which increased VLDL
production can lead to elevated LDL-C. While the previous example outlined VLDL
production driven by metabolic dysfunction, VLDL and LDL increases can be seen
for, effectively, the opposite reason as well.
Efficient Triglyceride Metabolism
In an individual with more optimal metabolic health, the
fate of a VLDL particle and the triglycerides within is different. The
frequently elevated blood glucose and chronically elevated insulin of a person
who overconsumes carbohydrates leads to an overreliance on carbohydrates for
energy, while the absence of these issues allows greater utilization of
triglycerides instead. Greater lipoprotein lipase (LPL) activity and the
flexibility to utilize fatty acids for energy means triglycerides are more
effectively liberated from VLDL at the body’s fat and muscle cells.1–3 As a result, VLDL lifespan is
decreased in a healthy person and the triglyceride rich lipoproteins (TGRL)
that characterize the unhealthy person’s metabolism are largely absent.
Recall the downstream effects of increased VLDL lifespan and
the proliferation of TGRL – In these instances, CETP mediates a trade of
triglycerides from VLDL particles to HDL and LDL particles to help facilitate
return of triglycerides to the liver. This process reduces HDL cholesterol and
ultimately shrinks HDL and LDL particles. In a person with good metabolic
health and few TGRL, this trade is largely unnecessary - The VLDL remnant
particles return to the liver with whatever triglycerides they retain without
needing to share the burden with HDL and LDL particles.4,5
This can be identified on a standard lipid panel by the
presence of lower triglycerides and lower VLDL cholesterol, the result of
efficient triglyceride uptake and a short VLDL lifespan. This desirable
metabolic efficiency can be maintained across a range of non-excessive
carbohydrate intake. Whether a person consumes no carbohydrates at all or
consumes a moderate amount in the context of a healthy-weight, active
lifestyle, reasonably efficient uptake of triglycerides will be maintained and
the deleterious effects of poor fatty acid metabolism avoided if carbohydrate
consumption is moderated relative to energy needs.6–10 The effects of
overconsumption, of course, are explained in the previous section.
Reliance on VLDL for Energy Delivery
What does any of this have to do with elevated LDL
cholesterol? Consider the more extreme instances of carbohydrate restriction,
which can generally be achieved two ways – through regular or extended fasting,
or through a long-term low carbohydrate diet. In either case, the effects are
basically the same; long-term stable blood sugar avoids the need to burn
carbohydrates for energy as a means of regulating blood sugar levels.
Meanwhile, chronically low insulin levels means enzymes such as hormone-sensitive
lipase (HSL - which is inhibited by insulin) are consistently active in
breaking down stored body fat – fatty acids which travel back to the liver to
be packaged as triglycerides in VLDL particles.11–15 Simultaneous elevated use of
fatty acids for energy and break down of stored body fat increases the number
of VLDL particles being produced to traffic triglycerides to cells of the body.
This is the same outcome – increased VLDL production
– we described in the previous section. The context, though, is entirely
different. While the unhealthy person is increasing VLDL production to compensate
for poor energy utilization and increased triglyceride return to the liver, the
healthy low-carb person is increasing VLDL production to match an increased
efficient use of triglycerides for energy. Because the VLDL particles being
produced to meet this need also contain cholesterol, they ultimately become LDL
particles that still contain that same cholesterol. LDL cholesterol thus rises,
while the quick uptake of triglycerides and short lifespan of the VLDL
particles means that measured triglycerides and VLDL cholesterol remain low.
This is an important point – even though this person is
producing “extra” VLDL-triglycerides, their measured triglyceride levels will
be low. Increasing triglyceride levels do not reflect increased production, but
instead decreased utilization. It is the poor uptake of triglycerides and the
lengthy lifespan of VLDL particles that contain them that causes triglyceride
levels to rise in a metabolically unhealthy person. But regardless of the root
cause, the increased VLDL production ultimately leads to increased LDL cholesterol
levels, as the cholesterol containing VLDL particles turn over to LDL particles
in both cases. In the next section, we’ll further explore the contextual
differences between these two disparate cases of elevated LDL cholesterol.
**Key Takeaways:
- Very low insulin levels that result from fasting or a low-carbohydrate diet result in consistent action of hormone-sensitive lipase in breaking down stored body fat
- Fatty acids freed from the body’s stores are transported back to the liver and packaged in VLDL particles
- This increase in VLDL production is matched by increased triglyceride utilization by the body’s cells, keeping measured triglyceride levels low
- The increase in cholesterol containing VLDL particles leads to an increase in LDL cholesterol as the VLDL quickly turn over to LDL particles
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