Lipogenesis is the metabolic process for creating new fat. It describes the conversion of non-fat sources, primarily excess carbohydrates, into fatty acids, which are then assembled into triglycerides for storage. This process acts as the body’s internal factory, taking surplus dietary materials and converting them into a stable, energy-dense form. This system ensures that extra energy is efficiently stockpiled in fat tissue.
How the Body Makes New Fat
The synthesis of new fatty acids from non-fat precursors is a process called de novo lipogenesis (DNL), which translates to fat creation “from scratch.” This pathway is most active in the liver and adipose (fat) tissue. While DNL in adipose tissue is common, in metabolic states like obesity, liver-based DNL becomes more pronounced as a response to an oversupply of energy.
When you consume more carbohydrates than your body needs for immediate energy or to replenish its glycogen storage, the excess is routed toward fat production. The journey begins when glucose is broken down into pyruvate, which enters the mitochondria and is converted into acetyl-CoA. This acetyl-CoA is the fundamental building block for making new fat.
Acetyl-CoA is transported out of the mitochondria into the cytoplasm, where the assembly work happens. An enzyme, acetyl-CoA carboxylase (ACC), converts acetyl-CoA into malonyl-CoA, a step that commits the building blocks to the fat synthesis pathway. Subsequently, the enzyme complex fatty acid synthase (FAS) adds these malonyl-CoA units together to create a 16-carbon fatty acid called palmitate.
Once palmitate and other fatty acids are formed, they are attached to a glycerol backbone to create triglycerides, the body’s main form of stored fat. These triglycerides can be kept in the liver or packaged into very-low-density lipoproteins (VLDL). VLDL particles are then shipped into the bloodstream to be stored in adipose tissue throughout the body.
Key Triggers of Lipogenesis
The hormone insulin is a primary director of lipogenesis. When blood sugar levels rise after a carbohydrate-rich meal, the pancreas releases insulin. This hormone signals the liver and fat cells to absorb glucose from the blood and initiate its conversion into fat. Insulin achieves this by upregulating the activity of lipogenic enzymes, including acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS).
Consuming more carbohydrates than the body can use for energy or store as glycogen is a direct trigger for DNL. Once the body’s glycogen reservoirs in the liver and muscles are full, any additional glucose is rerouted. The liver takes the lead in this conversion process, transforming the surplus glucose into fatty acids.
Fructose, a type of sugar found in table sugar and high-fructose corn syrup, is a potent activator of lipogenesis. Unlike glucose, which can be used by various cells, fructose is almost exclusively metabolized in the liver. This metabolic pathway rapidly converts fructose into the building blocks for fatty acids, bypassing some regulatory checkpoints that control glucose metabolism.
Lipogenesis is also governed at the genetic level by transcription factors, which are proteins that turn genes on or off. Two of these are SREBP-1c and ChREBP. Insulin stimulates SREBP-1c, which boosts the production of lipogenic enzymes, while ChREBP is activated by glucose and fructose metabolites. Fructose activates both of these transcription factors, amplifying its effect on fat production.
Regulating the Fat Production Process
The body also has mechanisms to turn off fat production. Glucagon is a hormone that works in opposition to insulin. When blood sugar levels are low, such as during fasting, the pancreas releases glucagon. This hormone signals the liver to halt fat storage and instead break down stored energy to release glucose into the blood.
Nutritional factors also help down-regulate lipogenesis. Certain dietary fats, specifically polyunsaturated fatty acids (PUFAs), can suppress the enzymes involved in creating new fat. PUFAs, found in sources like fish oil, walnuts, and flaxseeds, decrease the expression of lipogenic genes in the liver by inhibiting the transcription factor SREBP-1c.
This feedback system helps the body maintain balance. When dietary fats like PUFAs are present, they signal that there is no need to produce more fat from carbohydrates. This regulatory effect contrasts with diets high in saturated fats, which do not have the same inhibitory effect on lipogenic gene expression.
Health Implications of Excess Lipogenesis
When de novo lipogenesis becomes chronically overactive, it can lead to health issues. A primary consequence is the development of non-alcoholic fatty liver disease (NAFLD). In this condition, excessive fat accumulates in the liver, driven by elevated rates of DNL. Studies show that in individuals with NAFLD, DNL can account for as much as 26% of the fat stored in the liver.
Chronically elevated lipogenesis is also closely linked to insulin resistance. When the liver continuously produces and stores excess fat, it can become less responsive to insulin’s signals. This creates a cycle where insulin resistance leads to higher insulin levels, which in turn further stimulates DNL in the liver. This cycle is a precursor to type 2 diabetes.
Excessive DNL contributes to overall obesity and related metabolic problems. The constant conversion of excess carbohydrates into fat adds to the body’s fat stores. This process can lead to elevated levels of triglycerides in the bloodstream (dyslipidemia) and increased fat deposition in visceral areas, which are features of the metabolic syndrome.