I wrote here on fatty liver disease and its prevalence, and here on metabolic syndrome, a term encompassing excess weight gain, hypertension, elevated cholesterol and blood sugar levels. We’ve known for a long time that the two are correlated—where there is one, there is also the other, about 90% of the time.
But correlation is not the same as causation. Is there a causal relationship between the two? Specifically, for those who struggle with high blood sugar and lipid levels despite a seemingly healthy diet, might a fatty liver be to blame?
How You Get A Fatty Liver, and the Metabolic Syndrome Connection
Most of us think of the liver as just the site of detoxification, and it is that too, of course. But the liver is also one of the major sites of metabolic activity, keeping track of whether the body needs to store energy, or to make more of it. Other tissues important in fatty acid metabolism are fat cells (adipose tissue) and skeletal muscle, and they play a role in this process too.
The two main molecules involved in energy are glucose and fatty acids. If the liver senses that the body needs more glucose (because insulin levels are low), it either breaks down the glycogen it previously stored for just such an occasion, or if the glycogen stores are empty, the liver makes more glucose via a process called gluconeogenesis. Meanwhile, the adipose tissue gets the message that more energy is needed, and it releases fatty acids into the bloodstream. These travel to the skeletal muscles where they can be broken down and used for energy right away (via the mitochondria), or else they travel to the liver, where they get packaged into triglycerides. These are then inserted into very low density lipoproteins (VLDL), and released again to the tissues that need them.
If insulin levels are high, that signals that the body is in a fed state, and instead needs to store energy. The liver then converts glucose into either glycogen for future quick energy, or into fatty acids, which then get made into triglycerides. These in turn are packaged into LDL, which are then released into the bloodstream and stored, some in muscle and the rest in adipose tissue.
In cases of insulin resistance, insulin levels are always high, but the cells aren’t receiving the message. This means even in a well fed state, the liver is constantly making and releasing more glucose. This can cause high fasting glucose levels. Since more glucose also requires the pancreas to pump out more insulin, the insulin resistance problem only intensifies, in the liver and in the rest of the body.
Meanwhile, insulin resistant adipose tissue also won’t receive the message that there’s plenty of energy already, and it will release free fatty acids anyway. These make their way to the liver and skeletal muscle, but then they have nowhere to go… so they just accumulate. This not only means increased fat deposition, but as insulin resistance worsens, so too do fasting glucose, and lipid levels.
Indeed, this analysis identified 47 studies all pointing to a potential causal relationship between non-alcoholic fatty liver disease and later metabolic syndrome development.
How Fructose Can Cause Fatty Liver
You might notice that the process described above is a catch-22. Which comes first: the insulin resistance, or the fatty liver?
One major ingredient in the Standard American Diet may precede both, and that’s fructose. While insulin helps the liver determine whether the body is in a full or a fasted state, and thus whether glucose should be broken down or stored, fructose bypasses that regulatory step and goes straight into storage. This ramps up fatty liver, and thus, insulin resistance.
Fructose is found in fruit, though fruit is not (in moderation) a concerning source. The most concerning source is from high fructose corn syrup, though other sources include fruit juice (concentrated fructose from the fruit, without the fiber) and sucrose. Sucrose, or table sugar, is a glucose molecule connected to a fructose molecule—so any time you’re eating cane sugar, you’re getting fructose too. Even the “healthy” sweeteners are not guiltless here: agave is 90% fructose, while honey is about 40% fructose.
How Alcohol Can Cause Fatty Liver
One of the most common causes of fatty liver is caused by high alcohol intake. Unlike carbohydrates and fat which can either be used for energy or stored and used later for energy, alcohol doesn’t serve any useful purpose. It thus places a great burden on the liver to eliminate it quickly—so any real food that might otherwise get used for energy has to go straight to storage, because the liver is busy. This is why alcohol intake can so quickly lead to weight gain (though it actually leads to weight loss in alcoholics who forego food in favor of alcohol). Those 7 kCal/gram in alcohol effectively turn into heat, as best we can understand, since they can’t be used for anything else.
Meanwhile, because alcohol elimination requires a high demand for NAD+, other metabolic pathways that also require this nutrient slow down. The depletion of NAD+ leaves the liver far more susceptible to oxidative damage, as well.
Other Possible Causes of Fatty Liver
Rapid weight loss, usually from a very strict diet or bariatric surgery, can lead to the sudden efflux of free fatty acids from adipose tissue, all of which will end up in the liver. If there are more free fatty acids than the liver can handle all at once, it will get stored, which can also lead to fatty liver, insulin resistance, and subsequent metabolic syndrome.
SIBO (Small Intestine Bacterial Overgrowth) has been associated with fatty liver, too. This may be due to the bacterial effect upon bile, putting increased strain upon the liver, or may be due to the association between dysbiosis and insulin resistance.
Bisphenol A, found in the lining of canned goods, in plastics, and on printed receipts, has also been shown to induce fatty liver.
How do You Know if You Have a Fatty Liver?
The gold standard for diagnosis is a liver biopsy, but other signs and symptoms can also point toward the diagnosis.
A fatty liver will be picked up on ultrasound if the liver’s fat content is 10-15% or more. Otherwise, high fasting glucose or Type 2 diabetes plus two or more of the additional signs and symptoms of metabolic syndrome is a strong indication. These signs and symptoms include hypertension, abdominal obesity, high triglycerides, high VLDL, or low HDL. Liver enzyme elevation or high ferritin are often but not always present, as well.
What to Do About A Fatty Liver
The two most important changes to make to reverse fatty liver disease are to limit or cut out alcohol, and fructose intake. The former is fairly straightforward; the latter will essentially require eliminating sweetened beverages and most prepackaged foods, as the majority of them contain table sugar or fructose in some form.
Exercise also helps a great deal in reversing insulin resistance.
Since the mitochondria are so important for fatty acid breakdown, and they are often compromised due to oxidative damage in fatty liver, mitochondrial support may be indicated.
If you’ve struggled with symptoms of metabolic syndrome such as high fasting glucose, abnormal lipids, hypertension, or stubborn weight, particularly if you’ve “tried everything,” consider fatty liver as a possible underlying cause and direction for treatment.