Peripheral vs. Ectopic Fat

I went to an interesting presentation the other day by Dr. George Ioannou of the University of Washington, on obesity and liver disease. He made an interesting distinction between the health effects of two types of body fat. The first is called subcutaneous fat (or peripheral fat). It accumulates right under the skin and is evenly distributed over the body's surface area, including extremities. The second is called ectopic fat. Ectopic means "not where it's supposed to be". It accumulates in the abdominal region (beer belly), the liver, muscle tissue including the heart, the pancreas, and perhaps in lipid-rich deposits in the arteries. Subcutaneous fat can be measured by taking skinfold thickness in different places on the body, or sometimes by measuring arm or leg circumference. Ectopic fat can be measured by taking waist circumference.

It's an absolutely critical distinction, because ectopic fat associates with poor health outcomes while subcutaneous fat does not. In this recent study, waist circumference was associated with increased risk of death while arm and leg circumference were associated with a reduced risk of death. I think the limb circumference association in this particular study is probably confounded by muscle mass, but other studies have also shown a strong, consistent association between ectopic fat and risk of death, but not subcutaneous fat. The same goes for dementia and a number of other diseases. I think it's more than an epidemiological asssociation. Surgically removing the abdominal fat from mice prevents insulin resistance and prolongs their lifespan.

People with excess visceral fat are also much more likely to have fatty liver and cirrhosis. It makes sense if you think of them both as manifestations of ectopic fat. There's a spectrum of disorders that goes along with excess visceral fat and fatty liver: it's called the metabolic syndrome, and it affects a quarter of Americans (NHANES III). We already have a pretty good idea of what causes fatty liver, at least in lab animals: industrial vegetable oils and sugar. What's the most widely used animal model of metabolic syndrome? The sugar-fed rat. What are two of the main foods whose consumption has increased in recent decades? Vegetable oil and sugar. Hmm... Fatty liver is capable of causing insulin resistance and diabetes, according to a transgenic mouse that expresses a hepatitis C protein in its liver.

You want to keep your liver happy. All those blood tests they do in the doctor's office to see if you're healthy-- cholesterol levels, triglycerides, insulin, glucose-- reflect liver function to varying degrees.

Abdominal fat is a sign of ectopic fat distribution throughout the body, and its associated metabolic consequences. I think we know it's unhealthy on a subconscious level, because belly fat is not attractive whereas nicely distributed subcutaneous fat can be. If you have excess visceral fat, take it as a sign that your body does not like your current lifestyle. It might be time to think about changing your diet and exercise regime. Here are some ideas.

Polyunsaturated Fat Intake: Effects on the Heart and Brain

I'm revisiting the topic of the omega-6/omega-3 balance and total polyunsaturated fat (PUFA) intake because of some interesting studies I've gotten a hold of lately (thanks Robert). Two of the studies are in pigs, which I feel are a decent model organism for studying the effect of diet on health as it relates to humans. Pigs are omnivorous (although more slanted toward plant foods), have a similar digestive system to humans (although sturdier), are of similar size and fat composition to humans, and have been eating grains for about the same amount of time as humans.

In the last post on the omega-6/omega-3 balance, I came to the conclusion that a roughly balanced but relatively low intake of omega-6 and omega-3 fats is consistent with the diets of healthy non-industrial cultures. There were a few cultures that had a fairly high long-chain omega-3 intake from seafood (10% of calories), but none ate much omega-6.

The first study explores the effect of omega-6 and omega-3 fats on heart function. Dr. Sheila Innis and her group fed young male pigs three different diets:

1. An unbalanced, low PUFA diet. Pig chow with 1.2% linoleic acid (LA; the main omega-6 plant fat) and 0.06% alpha linolenic acid (ALA; the main omega-3 plant fat).
   
2. A balanced, low PUFA diet. Pig chow with 1.4% LA and 1.2% ALA.
3. An unbalanced, but better-than-average, "modern diet". Pig chow with 11.6% LA and 1.2% ALA.

After 30 days, they took a look at the pigs' hearts. Pigs from the first and third (unbalanced) groups contained more "pro-inflammatory" fats (arachidonic acid; AA) and less "anti-inflammatory" fats (EPA and DHA) than the second group. The first and third groups also experienced an excessive activation of "pro-inflammatory" proteins, such as COX-2, the enzyme inhibited by aspirin, ibuprofen and other NSAIDs.

The most striking finding of all was the difference in lipid peroxidation between groups. Lipid peroxidation is a measure of oxidative damage to cellular fats. In the balanced diet hearts, peroxidation was half the level found in the first group, and one-third the level found in the third group! This shows that omega-3 fats exert a powerful anti-oxidant effect that can be more than counteracted by excessive omega-6. Nitrosative stress, another type of damage, tracked with n-6 intake regardless of n-3, with the third group almost tripling the first two. I think this result is highly relevant to the long-term development of cardiac problems, and perhaps cardiovascular disease in general.

In another study with the same lead author Sanjoy Ghosh, rats fed a diet enriched in omega-6 from sunflower oil showed an increase in nitrosative damage, damage to mitochondrial DNA, and a decrease in maximum cardiac work capacity (i.e., their hearts were weaker). This is consistent with the previous study and shows that the mammalian heart does not like too much omega-6! The amount of sunflower oil these rats were eating (20% food by weight) is not far off from the amount of industrial oil the average American eats.

A third paper by Dr. Sheila Innis' group studied the effect of the omega-6 : omega-3 balance on the brain fat composition of pigs, and the development of neurons in vitro (in a culture dish). There were four diets, the first three similar to those in the first study:

1. Deficient. 1.2% LA and 0.05% ALA.
2. Contemporary. 10.7% LA and 1.1% ALA.
   
3. Evolutionary. 1.2% LA and 1.1% ALA.
4. Supplemented. The contemporary diet plus 0.3% AA and 0.3% DHA.

The first thing they looked at was the ability of the animals to convert ALA to DHA and concentrate it in the brain. DHA is critical for brain and eye development and maintenance. The evolutionary diet was most effective at putting DHA in the brain, with the supplemented diet a close second and the other three lagging behind. The evolutionary diet was the only one capable of elevating EPA, another important fatty acid derived from ALA. If typical fish oil rather than isolated DHA and AA had been given as the supplement, that may not have been the case. Overall, the fatty acid composition of the brain was quite different in the evolutionary group than the other three groups, which will certainly translate into a variety of effects on brain function.

The researchers then cultured neurons and showed that they require DHA to develop properly in culture, and that long-chain omega-6 fats are a poor substitute. Overall, the paper shows that the modern diet causes a major fatty acid imbalance in the brain, which is expected to lead to developmental problems and probably others as well. This can be partially corrected by supplementing with fish oil.

Together, these studies are a small glimpse of the countless effects we are having on every organ system, by eating fats that are unfamiliar to our pre-industrial bodies. In the next post, I'll put this information into the context of the modern human diet.

Visceral Fat and Dementia

This study was released today, demonstrating in 6,583 patients that visceral fat mass in the 40s predicts the risk of dementia in old age. Patients in the highest quintile (20% with the most visceral fat mass) had an almost three-fold higher risk of dementia than patients in the lowest quintile. Overall fat mass was less strongly correlated with dementia. This study is so timely, they must have heard about my blog post.

They used a measure of visceral fat called the "sagittal abdominal diameter", basically the distance from the back to the belly button. In other words, the beer belly.

What we're looking at is another facet of the pervasive "disease of civilization" that rolls into town on the same truck as sugar and white flour. Weston Price described it in 14 different cultures throughout the world in Nutrition and Physical Degeneration. Diabetes, cardiovascular disease, obesity, cancer and dementia all seem to come hand-in-hand. It's hard to say exactly what the root cause is, but the chain of causality seems to pass through visceral fat in many people.