De novo lipogenesis (DNL) is a metabolic process where the body creates new fat, specifically fatty acids, from non-fat sources, primarily carbohydrates. The term “de novo” means “from new,” and “lipogenesis” refers to the creation of fat. This natural and regulated pathway converts surplus nutrients into a form that can be efficiently stored for later use.
Understanding the Process of De Novo Lipogenesis
The process of de novo lipogenesis begins with simple molecules like acetyl-CoA, which are derived from the breakdown of carbohydrates, and to a lesser extent, certain amino acids. These acetyl-CoA units are then systematically assembled into longer chains to form fatty acids. This conversion occurs primarily in the cytosol.
Once fatty acids are synthesized, they are typically combined with glycerol to form triglycerides, which are the main form of fat stored in the body. The liver is the primary site for this conversion, converting excess carbohydrates into fatty acids that can then be stored as fat in adipose tissue. Adipose tissue, or body fat, also has the capacity for DNL, though its contribution is generally considered less significant than that of the liver.
The Body’s Triggers for DNL
The body initiates or increases de novo lipogenesis primarily as an energy storage mechanism when caloric intake surpasses immediate energy demands. This process is particularly stimulated by an abundance of dietary carbohydrates, especially once the body’s glycogen stores are full.
Insulin, a hormone released in response to elevated blood glucose levels after eating, plays a significant role in promoting DNL. Insulin stimulates the uptake of glucose by cells and activates enzymes involved in the lipogenic pathway. Compared to other macronutrients, fructose, a type of sugar, is a more potent inducer of hepatic lipogenesis than glucose.
De Novo Lipogenesis and Metabolic Health
De novo lipogenesis plays a normal and beneficial role in maintaining energy balance by converting excess carbohydrates into storable fat. This allows the body to efficiently manage periods of abundant food intake by building reserves for times when energy might be scarce. However, when DNL is excessively or chronically activated, often due to consistent overconsumption of calories and carbohydrates, it can contribute to several metabolic issues.
Excessive DNL can lead to non-alcoholic fatty liver disease (NAFLD), a condition characterized by fat accumulation in the liver. Studies show that DNL rates can be significantly upregulated in individuals with metabolic disorders like obesity and type 2 diabetes. This increased fat synthesis in the liver can impair liver function and contribute to overall metabolic dysfunction. Furthermore, elevated DNL can result in increased triglyceride levels in the blood, which is a risk factor for cardiovascular diseases.
The dysregulation of DNL is also linked to obesity and insulin resistance, as the continuous production of new fat can overwhelm the body’s storage capacity and interfere with insulin signaling. This means that while DNL is a natural process, its persistent overactivity, driven by dietary habits, can negatively impact the body’s metabolic state and contribute to the development or worsening of these health conditions. Increased DNL can contribute to ectopic fat deposition and may impair metabolic processes.
Dietary Strategies to Influence DNL
Managing dietary intake is a direct way to influence de novo lipogenesis and support metabolic health. A primary strategy involves reducing overall caloric intake, especially from refined carbohydrates and added sugars, as these are the main substrates for DNL. A low-sugar diet, for example, has been shown to reduce hepatic DNL.
Adopting a balanced macronutrient distribution can also help modulate DNL activity. Diets rich in fiber, healthy fats, polyphenols, and certain vitamins can reduce liver fat accumulation by inhibiting DNL. In contrast, high-fat diets have been shown to suppress DNL, suggesting that the type and quantity of dietary fat also play a role in regulating this process. Focusing on whole, unprocessed foods can naturally limit the intake of readily available carbohydrates that fuel DNL, contributing to better metabolic control.