Weight Management: Nonalcoholic Fatty Liver Disease--Cause and Effect

The liver is one of the largest organs, charged with many tasks, including metabolizing food-based derivatives and hormones, assimilating and storing fat-soluble vitamins, and purifying and clearing waste products, toxins, and drugs.

Yet there exists a dramatic condition that affects the livers of millions of people-nonalcoholic fatty liver disease (NAFLD). When this condition exists and goes unchecked, it worsens, directly affecting cardiovascular, blood sugar health, and even obesity.

NAFLD is clinically defined as an accumulation of liver fat mass at 5% or higher in individuals who have no history of alcohol abuse, but medical researchers have determined that fatty liver disease could even be present in those with liver fat mass below 5%.

Histologically, it’s classified by severity as steatosis (accumulation of fat in the liver cells) or nonalcoholic steatohepatitis (NASH; steatosis and inflammation). NAFLD may progress to liver cancer in the following manner: from a normal liver to steatosis, NASH, liver cirrhosis, and then liver cancer.

The NAFLD Population

Epidemiological research shows that NAFLD affects 25% of the non-obese population and 75% of the obese population. NAFLD usually occurs during middle age, but more children and young adults are being diagnosed with the condition.

Common risk factors associated with NAFLD include obesity (body mass index greater than 40 kg/m2) with a visceral pattern of fat deposits, increased waist circumference, type 2 diabetes, elevated blood pressure, increased blood levels of liver enzymes and triglycerides, and low levels of high-density lipoproteins.

Some authors interpret the cluster of above clinical conditions, characteristic of metabolic syndrome, as a liver manifestation of this condition. Accordingly, metabolic syndrome does pose an increased risk of NAFLD. Other symptoms indicative of advanced NAFLD include increased serum levels of inflammation markers like C-reactive protein and insulin resistance.

Still, NAFLD is often not clinically obvious, and many diagnosed patients may be asymptomatic. In one U.S. study, magnetic resonance imaging identified NAFLD in 31% of subjects-even though 79% of these cases had normal liver function.

The Diet Factor

The liver is affected unfavorably by a diet high in simple carbohydrates that exert a high glycemic index; food additives and chemicals; excessive trans and saturated fats; high-fructose corn syrup and other sugars; and very little fresh vegetables, fruits, seeds, and whole grains. A diet low in nutrients and abundant in antinutrients causes changes in normally hormonal and biochemical processes and pathways as well as gut flora, which leads to overgrowth of pathogenic bacteria in the gut, causing fermentation and production of toxins.

A low-fiber diet also hampers the absorption of bile acids, cholesterol, and triglycerides (fat) excreted from the liver into the gastrointestinal tract. This results in excessive reabsorption of bile acids, cholesterol, and fatty acids into the liver, instigating fat accumulation in liver cells, leading to NAFLD.

In obese individuals, excess dietary fatty acids impair the ability of liver cells to convert fatty acids into energy, which can cause oxidative stress. Increased levels of the enzyme angiotensin II may further contribute to oxidative damage and higher blood pressure.

The unutilized fatty acids turn cytotoxic, triggering cell death (apoptosis) of the hepatocytes. The fatty acids activate the lysosomal pathway of liver-cell death, beginning with lysosomal membrane permeabilization (LMP) and the release of cell-destructive enzymes (e.g., cathepsins) from the lysosomes to the cell cytoplasm.

Ordinarily, an LMP event may trigger cell death proteins (caspases) that orchestrate apoptosis. However, in the case of NAFLD, a massive LMP often results in cell death without the benefit of orderly caspase activation. Instead, necrotic cell death produces pro-inflammatory events. This instigates the progression of NAFLD from nonalcoholic steatosis to steatohepatitis. Inflammation, necrotic cell death, and fibrosis represent key features of NAFLD pathology which lead to insulin resistance, diabetes type 2, metabolic syndrome, and obesity.

Improved liver health is measured by a decrease in the fat content of the liver, as well as normalized enzyme ratio and activity, which is related to the reduction in visceral fat.

More physicians are now testing for fatty liver and enzyme profiles. This leads to significant market opportunities for manufacturers of dietary supplements and functional foods/beverages. 

To read the feature article on Weight Management, click here.