Fatty acid synthase (FAS) is a complex enzyme system within the human body. Its primary function involves creating long-chain fatty acids from smaller precursor molecules, known as de novo lipogenesis. This pathway is fundamental to how the body manages and stores energy. FAS activity contributes to various cellular processes, beyond energy storage.
The Function of Fatty Acid Synthase
Fatty acid synthase operates as a molecular assembly line within cells. It converts excess carbohydrates and proteins, which are broken down into acetyl-CoA, malonyl-CoA, and NADPH. Through a series of reactions, FAS systematically builds these units into palmitate, a 16-carbon saturated fatty acid. This newly synthesized palmitate serves several purposes in the body.
Palmitate can be stored as triglycerides, the main form of fat reserves in the body, providing a concentrated source of energy. These triglycerides are often packaged into lipid droplets within cells or secreted as very low-density lipoproteins. Beyond energy storage, palmitate also acts as a building block for various cellular components, including cell membranes. This ensures cells have the necessary lipids for growth, repair, and proper function.
How Fatty Acid Synthase is Regulated
The body tightly controls fatty acid synthase activity, adjusting production based on physiological needs. Two primary factors regulate FAS: dietary intake and hormonal signals. When diets are rich in carbohydrates or high in calories, the body increases FAS production. This converts excess energy from nutrients into fatty acids for storage, preventing an overload of circulating sugars.
Hormonal signals also orchestrate FAS activity. Insulin, released after a meal due to elevated blood glucose, acts as an “on” switch for FAS. Insulin signals the body to synthesize and store fat, aligning with nutrient abundance. Conversely, hormones like glucagon, present during fasting or low blood sugar, act as an “off” switch, suppressing FAS activity to encourage stored energy utilization rather than new fat synthesis.
The Link to Metabolic Disease
Chronic overactivity of fatty acid synthase can contribute to several metabolic conditions. When FAS is overactive, it leads to excessive fat production and accumulation within the body. This heightened lipogenesis contributes to obesity, characterized by increased body fat. Continuous fatty acid synthesis can overwhelm the body’s storage capacity.
Dysregulated FAS activity can lead to non-alcoholic fatty liver disease (NAFLD), where fat abnormally accumulates in the liver. This condition can progress to severe liver damage if unaddressed. Additionally, overactive FAS is linked to insulin resistance, where cells become less responsive to insulin’s signals. Insulin resistance is a precursor to type 2 diabetes, highlighting FAS dysregulation’s broader impact on metabolic health.
The Role of Fatty Acid Synthase in Cancer
Many types of cancer cells exhibit significantly increased levels of fatty acid synthase, a notable metabolic alteration compared to normal cells. This heightened FAS activity provides cancer cells with a constant, abundant supply of new fatty acids. These fatty acids are rapidly incorporated into cell membranes, which are continuously expanded as cancer cells divide and multiply at an accelerated rate. Extensive membrane synthesis fueled by FAS is tied to tumor growth and proliferation.
Cancer cells rely on this endogenous fatty acid synthesis to meet their high demand for building blocks, even when external lipid sources are limited. This dependency makes FAS a valuable target in cancer research. High FAS levels in tumors are frequently associated with a poorer prognosis for patients, indicating a more aggressive disease course. The enzyme’s role in fueling rapid, uncontrolled cell division distinguishes its involvement in cancer from its general metabolic functions.
Therapeutic Targeting of Fatty Acid Synthase
Given the role of fatty acid synthase in metabolic diseases and cancer, researchers are exploring strategies to modulate its activity for therapeutic benefit. One promising approach involves FAS inhibitors, compounds designed to block the enzyme’s function. These inhibitors aim to disrupt the excessive fatty acid synthesis that characterizes certain disease states.
Because many cancer cells are highly dependent on FAS for their rapid growth and survival, FAS inhibitors are being investigated as potential anti-cancer therapies. Preclinical studies have shown that inhibiting FAS can induce programmed cell death in cancer cells and reduce tumor growth in models. Beyond cancer, FAS inhibitors also show promise for treating metabolic conditions like non-alcoholic fatty liver disease, by reducing fat accumulation in the liver. This therapeutic strategy represents a forward-looking area of research.