Low high-density lipoproteins (HDL) AS VLDL PARTICLES circulate through the bloodstream, insulin stimulates the hormone lipoprotein lipase (LPL), which is found in the small blood vessels of muscles, adipocytes, and the heart. This LPL transports the triglycerides out of the blood into adipocytes for safe storage. As VLDL releases its triglycerides, the particles become smaller and
denser; now called VLDL remnants, the liver reabsorbs them.
In turn, the liver releases these remnants back into the bloodstream as low-density lipoproteins (LDL), which are measured by standard blood cholesterol panels and are classically considered the “bad” cholesterol.
High blood triglycerides strongly and independently predict cardiovascular disease,18 almost as powerfully as LDL, the marker that typically concerns doctors and patients most.
Hypertriglyceridemia increases the risk of heart disease by as much as 61 percent,19 and the average triglyceride level has been rising inexorably in the United States since 1976.
An estimated 31 percent of adult Americans have elevated triglyceride levels,20 though hypertriglyceridemia by itself is unlikely to cause heart disease since medications that lower triglycerides do not reduce the risk of cardiovascular disease.21 High levels of LDL are pointedly not one of the criteria for developing metabolic syndrome.
Instead, the other cholesterol component of the metabolic syndrome is the high-density lipoproteins (HDL, the “good” cholesterol).
The landmark Framingham studies established that low levels of HDL are strongly associated with heart disease22 and predicts heart disease much more powerfully than LDL.
Low levels of HDL are found in close association with high levels of triglycerides: more than 50 percent of patients with low HDL also have high triglycerides.
High levels of triglycerides activate the enzyme cholesterol ester transfer protein (CETP), which reduces HDL levels.
Given this close association with triglycerides, it should be no surprise that low- carbohydrate diets raise HDL,23 even independent of weight loss.
As with triglycerides, low HDL does not cause heart disease, but is a powerful indicator.24 What is clear, however, is that the lipid profile typical of the metabolic syndrome, high triglycerides and low HDL, results from the excess of VLDL,25 which ultimately stems from hyperinsulinemia, which ultimately stems from eating too much glucose and fructose.
Again, too much sugar.
Figure 9.2.
Hormonal obesity VII: Fatty liver → low HDL
Abdominal obesity THE ADIPOCYTES GET larger as they take up the triglycerides for storage.
This is not particularly dangerous to our health since adipocytes are designed to store fat.
But being too fat is dangerous from an evolutionary standpoint, because fat animals get eaten.
The adipocytes protect themselves against overexpansion by releasing the hormone leptin.
This signals the hypothalamic area of the brain that we need to lose fat.
We stop eating, insulin drops, and we lose weight.
In this way, obesity serves as the first line of defense against hyperinsulinemia.
Insulin encourages fat storage, whereas leptin strives to reduce it.
If leptin proves more powerful, then weight is lost and fat mass decreases.
This negative feedback loop should keep us at an ideal weight.
So how do we become obese?
This problem occurs when insulin stays too high for too long, which is typical in insulin resistance.
If you have too much body fat, leptin is released, which decreases food intake.
Insulin should fall, and you should lose weight.
In insulin- resistant states, insulin levels stay persistently high, which tells the body to keep storing fat.
Leptin therefore stays persistently high too.
As with all hormones, exposure creates resistance, so persistently high leptin creates the leptin resistance found in common obesity.
It’s a tug of war between insulin and leptin, and if you are eating too much sugar, ultimately, insulin wins.
Insulin allows glucose to move from the blood into the cells.
Persistent hyperinsulinemia crams even more glucose into the liver, creating even
more new fat.
When hyperinsulinemia persists, the pedal-to-the-metal production of new fat overwhelms the adipocytes.
Fat backs up, causing fatty liver.
Fructose is directly converted to liver fat and leads to the next stage, insulin resistance.
If allowed to continue, the engorged liver will become distended and injured.
The liver cell cannot safely handle any more glucose, yet insulin is still pushing really, really hard to shove more inside.
The liver’s only option is to refuse entry.
This is known as insulin resistance, and it develops as the body’s second line of defense against hyperinsulinemia.
The liver feverishly tries to relieve the fatty congestion by exporting triglycerides, and blood levels increase in a classic sign of metabolic syndrome.
Ectopic fat accumulates in other organs, such as the pancreas, kidneys, heart, and muscle.
The predominance of fat around the abdomen becomes noticeable as an increase in waist size, which can be described as a beer belly but more recently is being called a “wheat belly.” This abdominal, or visceral, fat is the most important predictor of metabolic syndrome.26 Surgical removal of visceral fat reverses insulin resistance,27 whereas removal of subcutaneous fat has no such metabolic benefits.28
High blood glucose IN ADDITION TO accumulating in the abdominal region, fat accumulates within organs that are not designed to store it.
Distention of the liver and skeletal muscles with fat increases insulin resistance, even though the pancreas increases insulin to keep blood glucose levels relatively normal.
But that’s not the end of the story.
Ectopic fat clogs the pancreas and interferes with normal functioning, so insulin levels fall.
When the fatty pancreas fails to produce the compensatory hyperinsulinemia, blood glucose skyrockets and becomes symptomatic when it exceeds the renal threshold.
Glucose spills out into the urine, and the classic symptoms of diabetes, excessive urination, thirst, and weight loss, appear.
High blood pressure (hypertension) HIGH BLOOD PRESURE is often called “the silent killer” because there are no symptoms, yet it contributes heavily to the development of heart attacks
and strokes.
Most cases are called essential hypertension because no specific cause can be found for its development; however, hyperinsulinemia plays a key role.
Researchers first reported disproportionately high blood insulin concentration in hypertensive patients more than fifty years ago.29 Since then, multiple studies, such as the European Group Study of Insulin Resistance,30 have confirmed this relationship.
High and rising insulin levels doubled the risk of developing hypertension in those who previously had normal blood pressure.31 A complete review of all available studies estimates that hyperinsulinemia increases the risk of hypertension by 63 percent.32 Insulin increases blood pressure through multiple mechanisms.33 Insulin increases the cardiac output, the contractile force of the heart34 , and the volume of blood in circulation by enhancing the kidney’s ability to reabsorb sodium (salt).
In addition, insulin stimulates the secretion of anti-diuretic hormone, which helps the body to reabsorb water.
Together, this salt and water retention mechanism increases blood volume and thus causes higher blood pressure.
Insulin also constricts blood vessels, increasing the pressure inside.35 Figure 9.3.