Understanding the Metabolic Process of Glucose to Triglycerides

December 23, 2025 •

3 min read

In metabolic conditions such as obesity and type 2 diabetes, the rate of converting glucose to triglycerides can be five times higher than in healthy individuals. This metabolic pathway, scientifically known as de novo lipogenesis (DNL), describes how the body handles surplus glucose by turning it into fat for long-term storage.

Quick Summary

The conversion of excess glucose into triglycerides is termed de novo lipogenesis (DNL), an anabolic process occurring in the liver and fat tissue. This process involves converting glucose into fatty acid precursors, then synthesizing triglycerides for storage.

Key Points

Name of the Process: The conversion of glucose to triglycerides is known as de novo lipogenesis (DNL), a complex metabolic pathway.
Primary Locations: This process occurs primarily in the liver and adipose (fat) tissue, converting excess glucose from carbohydrates into storable fat.
Hormonal Regulation: DNL is primarily stimulated by insulin after meals rich in carbohydrates and is inhibited by hormones like glucagon during periods of fasting.
Dysregulation Consequences: Excessive DNL, especially in the liver, is linked to metabolic disorders such as fatty liver disease, obesity, and insulin resistance.
Differential Tissue Roles: DNL activity and regulation differ between the liver and adipose tissue, with hepatic DNL often dysregulated in metabolic disease, while adipose DNL can produce beneficial signaling molecules.
Key Enzymes: Critical enzymes involved in the process include Acetyl-CoA Carboxylase (ACC) and Fatty Acid Synthase (FAS), both regulated by hormones and transcription factors.

What Is De Novo Lipogenesis (DNL)?

De novo lipogenesis, or DNL, is the process where the body synthesizes fatty acids and triglycerides from non-fat sources, primarily carbohydrates. Essentially, it's the creation of new fat molecules from simple sugars when energy intake is higher than needed. While a normal way for the body to store energy, too much DNL can lead to metabolic issues like fatty liver disease, obesity, and insulin resistance.

Key Steps in the Glucose-to-Triglyceride Pathway

The conversion of glucose to triglycerides is a multi-step process mainly occurring in liver and fat cells. Insulin, which is released after eating carbohydrates, plays a key role in promoting this process.

Glycolysis and Pyruvate Formation: Excess glucose from carbohydrates is broken down through glycolysis, producing pyruvate.
Entry into the Mitochondria: Pyruvate enters the mitochondria and is converted to acetyl-CoA.
Citrate Shuttle: Acetyl-CoA is converted to citrate to move out of the mitochondria into the cytoplasm, where fat synthesis happens.
Cytoplasmic Acetyl-CoA Regeneration: In the cytoplasm, citrate is broken back down into acetyl-CoA and oxaloacetate by ATP-citrate lyase.
Malonyl-CoA Synthesis: Cytoplasmic acetyl-CoA becomes malonyl-CoA, a crucial step in fatty acid synthesis regulated by the enzyme acetyl-CoA carboxylase (ACC) and influenced by insulin.
Fatty Acid Synthesis: The enzyme complex fatty acid synthase (FAS) builds fatty acid chains from acetyl-CoA and malonyl-CoA, mainly producing palmitate.
Triglyceride Assembly: Newly made fatty acids combine with a glycerol backbone (also from glucose) in the endoplasmic reticulum to form triglycerides.
Storage and Export: Triglycerides are stored in fat cells or, from the liver, packaged into VLDL and sent into the bloodstream for storage in adipose tissue.

Comparison of DNL in the Liver vs. Adipose Tissue

DNL happens in both the liver and fat tissue, but its activity differs, especially in conditions like obesity and insulin resistance.


Feature	Hepatic DNL (Liver)	Adipose DNL (Fat Tissue)
Primary Role	Converts excess carbs into fatty acids for export and storage.	Stores fat from food and VLDL from the liver.
Regulation	Highly influenced by carb intake and insulin. Can be too high with insulin resistance.	Less affected by carb intake in people compared to the liver.
Impact in Obesity	Often increased and not properly controlled, contributing to fatty liver disease (NAFLD) and high blood lipids.	Can be reduced or not work properly in obesity, potentially making systemic insulin resistance worse.
Storage/Output	Packages triglycerides into VLDL to distribute throughout the body.	Holds most of the body's triglycerides for energy storage.

The Role of DNL in Health and Disease

Energy Balance: Normally, DNL helps the body manage energy by storing extra energy as fat when a lot of carbohydrates are eaten. Unlike glycogen storage, fat storage through DNL has a large capacity.
Dysregulation in Metabolic Disorders: Ongoing excess energy intake can disrupt DNL. In conditions like obesity, too much liver DNL can increase VLDL, leading to high blood triglyceride levels. This is a key part of metabolic syndrome and insulin resistance.
Inflammation: In fat tissue, reduced DNL in obesity might be negative. Some research suggests DNL in fat cells produces helpful signaling lipids (lipokines) that can improve insulin sensitivity and reduce inflammation. Thus, impaired fat tissue DNL could harm overall metabolic health.

Hormonal and Transcriptional Control

Several hormones and transcription factors regulate DNL:

Insulin: Insulin is the main hormone that stimulates DNL. After high blood glucose, insulin promotes glucose uptake and boosts the activity of key DNL enzymes like ACC and FAS.
Glucagon and AMPK: Glucagon inhibits DNL during fasting or low blood glucose. It activates AMPK, which in turn inhibits ACC, stopping fatty acid synthesis.
Transcription Factors: SREBP-1c and ChREBP are key factors that control the genes involved in DNL. Insulin primarily activates SREBP-1c in the liver, while glucose metabolites activate ChREBP, especially in fat tissue.

Conclusion

The conversion of glucose to triglycerides, known as de novo lipogenesis (DNL), is a basic metabolic process for storing energy long-term. Although a vital function, problems with DNL are central to many metabolic diseases today, including fatty liver disease, obesity, and type 2 diabetes. Understanding the steps and how hormones and genes control DNL helps explain these conditions. Ongoing research into the specific roles of DNL in different tissues and its signaling molecules may lead to new ways to treat metabolic diseases. Regulation and Metabolic Significance of De Novo Lipogenesis

Frequently Asked Questions

The main purpose of de novo lipogenesis is to convert excess dietary energy, particularly from carbohydrates, into fatty acids and subsequently triglycerides for long-term storage in adipose tissue.

De novo lipogenesis primarily occurs in the liver (hepatocytes) and adipose tissue (adipocytes), though it can also happen to a lesser extent in other tissues.

Insulin is a critical promoter of de novo lipogenesis. When blood glucose levels rise after a meal, insulin stimulates glucose uptake and activates the key enzymes, like Acetyl-CoA Carboxylase (ACC) and Fatty Acid Synthase (FAS), that drive the conversion process.

The conversion is a normal physiological process for energy storage. However, if an individual consumes a chronic excess of calories, particularly from carbohydrates, the over-activity of de novo lipogenesis can become pathological and contribute to diseases like obesity and fatty liver.

Once triglycerides are synthesized from glucose in the liver, they are packaged into very low-density lipoproteins (VLDL) and transported through the bloodstream to adipose tissue, where they are stored in fat cells for future energy needs.

Yes, fructose is a potent stimulator of de novo lipogenesis. Unlike glucose, it bypasses some regulatory steps in glycolysis, leading to an accelerated production of lipogenic precursors and triglycerides in the liver.

Exercise reduces de novo lipogenesis by increasing glucose uptake and utilization in muscles for immediate energy, decreasing circulating insulin levels, and promoting fat oxidation rather than synthesis.