De novo Lipogenesis

“Carbs make you fat” is a quote many people have heard if you’ve been in the health or fitness field in any capacity. Luckily, if you are educated in bioenergetics and physiology, you should have a good understanding of how the carb to fat “hypothesis” needs to be more nuanced. In this article, we will delve into the process of de novo lipogenesis, what it is, why it occurs, and understand the physiological occurrence.

What is Denovo Lipogenesis??

De novo lipogenesis is the process of transforming carbohydrates to lipids, fats [1].

Why does it occur?

Carbohydrates are converted to lipids, because lipids are more easily stored and are a more energy dense molecule, providing substantially more adenosine triphosphate (ATP) per molecule (30-38 vs 108+ molecules) [1][2][3].

When does it occur?

When carbohydrate intake surpasses need (and energy need), and when fat intake is insufficient [4].

Where does it occur?

In the hepatocytes (liver cells) and the adipocytes (fat cells), primarily; although, most cells can undergo de novo lipogenesis [2][4][9].

Adipocytes (fat cells)

Understanding the Physiology

Without getting into the Reverse Randle Cycle to any large extent, we know that once glucose enters the cell and undergoes glycolysis, it enters the tricarboxylic acid cycle as acetyl CoA and in the first step is converted to citrate via citrate synthase [5]. Citrate can then be exported from the mitochondria via a citrate antiporter in the membrane on its way to the cytoplasm of the cell [5][6]. In the cytoplasm, citrate is acted upon by ATP-Acetyl CoA Lyase and, using ATP and biotin (Vitamin B7), converted back to acetyl CoA and oxaloacetate [7][8]. As acetyl CoA, Acetyl CoA Carboxylase converts the molecule to malonyl CoA, which inhibits the mitochondrial carnitine palmitoyltransferase, or CPT; a protein "gate" that allows fatty acids into the mitochondria to be oxidized for energy [2]. Finally, through Fatty Acid Synthase, malonyl CoA is converted to the non-essential fatty acid palmitate, which is then open for modification to various fatty acid forms [2][4][8].


Lipogenesis is regulated by sheer absolute amounts of glucose, with more being favorable and less inhibiting the process [9]. In the same vein, lipogenesis is active during high insulin release, postprandially (after eating), and down during glucagon release [9]. Similarly, high leptin and growth hormone both inhibit lipogenesis, while acylation stimulating protein, released from the adipocytes in an autocrine fashion, stimulates it [9].

Genetically, lipogenesis is largely controlled by a transcription factor called sterol regulatory element–binding protein (SREBP), which binds to fatty acid synthetic genes and increases their transcription, leading to more synthesis proteins [10]. SREBP-1 increases the transcription of Acetyl-CoA Lyase, Acetyl CoA Carboxylase, and Fatty Acid Synthase [10].


Author: Nicolas Verhoeven

[1] Herman, M. E. (2012, February). Adipose tissue de novo lipogenesis. Retrieved from

[2] Chapter 16 : Oxidation of Fatty Acids. (n.d.). Retrieved from

[3] ATP Production of One Glucose. (n.d.). Retrieved from

[4] Hellerstein, M. (1999). De novo lipogenesis in humans: metabolic and regulatory aspects. European Journal of Clinical Nutrition, 53(S1), s53-s65. doi:10.1038/sj.ejcn.1600744

[5] Pelley, J. W. (2012). 10 – Fatty Acid and Triglyceride Metabolism. Retrieved from Elsevier's Integrated Biochemistry website:

[6] Sun, J. (2010). Mitochondrial and Plasma Membrane Citrate Transporters: Discovery of Selective Inhibitors and Application to Structure/Function Analysis. Molecular & Cellular Pharmacology, 2(3), 101-110. Retrieved from

[7] ACLY ATP citrate lyase [Homo sapiens (human)] - Gene - NCBI. (2018). In National Center for Biotechnology Information. Retrieved from

[8] Medh, J. D. (n.d.). Fatty Acid Biosynthesis [PowerPoint]. Retrieved from

[9] Kersten, S. (2001). Mechanisms of nutritional and hormonal regulation of lipogenesis. EMBO reports, 2(4), 282-286. doi:10.1093/embo-reports/kve071

[10] Horton, J. D., Goldstein, J. L., & Brown, M. S. (2002). SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. Journal of Clinical Investigation, 109(9), 1125-1131. doi:10.1172/jci15593


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