Non-alcoholic fatty liver: How obesity leads to fatty liver disease

Non-Alcoholic Fatty Liver Disease (NAFLD) is a condition in which fat accumulates inside of the liver. If the disease is allowed to progress it can lead to dysfunction of the liver cells and eventually cause liver injury. NAFLD is a common condition, affecting approximately 1 in 3 adults in the United States. While the exact mechanism by which NAFLD develops is not yet fully understood, there is a strong correlation between excess body weight and non-alcoholic fatty liver disease. NAFLD is often a silent disease without obvious symptoms, but it can increase a person’s risk of a number of metabolic and cardiovascular diseases. NAFLD prevalence is increasing rapidly around the world. It is quickly becoming the leading indication for liver transplant and is the fastest growing cause of liver cancer in the United States. Therefore, NAFLD is an important disease to prevent, identify, and treat. 

What are the common symptoms of non-alcoholic fatty Lliver disease?

NAFLD usually does not cause any symptoms, therefore most people will not know they have NAFLD unless they get tested. Medical providers often screen for NAFLD by checking blood levels of liver enzymes. If elevated, a medical provider may order an imaging study which is used to make the NAFLD diagnosis. Depending on the severity of the disease, a biopsy may sometimes be performed to help determine how much the disease has progressed.

NAFLD is split into two categories: non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). NAFL indicates fat in the liver without scarring or inflammation. If this accumulation of fat is not treated and allowed to progress, it can cause toxicity to the liver cells and progress to a condition called NASH. NASH is a condition in which scarring or inflammation is present in the liver. 70-80% of people with NAFL never develop further disease, however, about 20-30% of cases will progress to NASH. In rare cases, NASH can progress further into cirrhosis (liver damage where healthy cells are replaced by scar tissue), liver failure, or liver cancer. 

While NAFL and NASH are often asymptomatic, some people may develop pain in their right upper abdomen or feel fatigued. If there is severe disease present, symptoms of advanced cirrhosis or liver failure may include:

• Significant fatigue, weakness, or tiredness
• Unintended weight loss and loss of appetite
• Fluid buildup in the abdomen, called ascites
• Swelling in the feet or lower legs, called edema
• Yellowing of the skin or eyes
• Spider-like blood vessels on the skin
• Confusion 

How does obesity lead to non-alcoholic fatty liver disease?

The disease of obesity is the most common and best documented risk factor for development of NAFLD. In fact, an estimated 50-90% of patients who have obesity also have NAFLD. Studies show that the higher a person’s BMI, the higher risk of having NAFLD. A person with a BMI of 30-32.5 has a 5-9 fold increased risk of NAFLD, and a person with a BMI of 37.5-40 has a 10-14 fold increased risk of NAFLD. The link is likely bi-directional and not yet fully understood, with an increase in BMI increasing a person’s likelihood of developing NAFLD and vice-versa. Many of the same risk factors for weight gain are also risk factors for NAFLD, including insulin resistance, unhealthy dietary patterns, and sedentary lifestyle.

Insulin resistance

Insulin resistance occurs when our cells no longer respond properly to signals for an important energy storage hormone called insulin. If allowed to progress, this can lead to type 2 diabetes and numerous other metabolic diseases. In the liver, insulin resistance can cause cells to inappropriately create more fat (called de-novo lipogenesis) and break down less fat (called lipolysis), leading to NAFLD. NAFLD, in turn, can also worsen insulin resistance, leading to a vicious cycle of metabolic disease. In fact, studies show that approximately 70% of people with type 2 diabetes also have NAFLD. 

Unhealthy dietary habits

Diets that are high in processed foods, especially those high in saturated fats and added sugars, have been linked to the development of NAFLD. One recent study showed that both moderate and high intake of ultra-processed foods were significantly associated with development of NAFLD.

Sedentary lifestyle

Prolonged sitting times and low levels of physical activity have been strongly associated with prevalence of NAFLD. These associations seem to occur in a dose-dependent manner, meaning that the more time a person spends sitting and the less time they spend physically active throughout the day, the more likely they are to develop NAFLD.

Non-alcoholic fatty liver disease prevention and treatment

While there are currently no FDA-approved medications for the treatment of NAFLD, the great news is that NAFLD is both preventable and treatable with lifestyle modifications and weight reduction. 

Weight loss

 Studies show that a weight loss of >10% body weight can reduce fat in the liver and improve fibrosis, or scarring, of the liver. However, risk factors begin to improve with as little as 3-5% weight reduction. Whether this weight loss is achieved through lifestyle modifications alone, or in combination with anti-obesity medications or bariatric surgery, weight reduction is currently the most effective treatment option to improve or even reverse NAFLD for most patients. 

Dietary changes

While many dietary patterns have been studied for reducing NAFLD severity, the effective strategies have more in common than they differ. Dietary changes aimed at reducing intake of highly processed foods and beverages (especially those high in added sugars and saturated fats) and replacing these with more whole, real foods, including ample vegetables, fruits, lean proteins, high-fiber starches and healthy fats (such as those in olive oil, nuts and fatty fish) are a great place to start. While these changes can feel daunting, the plate method is one helpful guide for making these changes more easily. 

Physical activity

 Multiple studies show that both aerobic and resistance training exercises are effective for improvement in NAFLD. Regular physical activity helps to improve NAFLD severity by reducing insulin resistance, improving inflammation and reducing body weight. It’s important to note that physical activity helps to improve NAFLD even if no weight loss is achieved!

Medications

 While there are currently no FDA-approved medications for treating NAFLD, many are currently being studied for this use. GLP-1 medications such as Wegovy®, Saxenda®, and Ozempic®, have been shown to improve NAFLD severity, probably related to their beneficial effect on body weight and insulin resistance, and there is currently research underway on the potential use of these medications for the treatment of NAFLD. 

Managing obesity for better health

NAFLD is a common disease worldwide that can increase a person’s risk for developing liver injury and other metabolic diseases. While the association between obesity and NAFLD is not yet fully understood, we know that excess body weight significantly increases a person’s risk of developing NAFLD and that weight reduction is currently the most effective treatment option for NAFLD. 

Losing weight can be challenging for many different reasons, but Form Health is here to help.  At Form Health, you are paired with a board-certified  Obesity Medicine specialist and a Registered Dietitian who utilize their expertise in weight management to develop a personalized weight loss plan tailored to your needs. They address behavioral support, nutrition, physical activity, and, if appropriate, may prescribe FDA-approved weight loss medications. Take our quiz to see if you qualify!

Wegovy®, Saxenda® and Ozempic® are registered trademarks of Novo Nordisk A/S.