From the Research
The key reducing equivalent required for lipogenesis is NADPH, which is generated through various pathways, including the pentose phosphate pathway, with serine catabolism playing a crucial role in liver NADPH production, as evidenced by a recent study 1.
Importance of NADPH in Lipogenesis
NADPH serves as the essential electron donor for reductive biosynthesis of fatty acids, providing the reducing power needed to convert acetyl-CoA to fatty acids during lipogenesis. The primary sources of NADPH in the body include:
- The pentose phosphate pathway
- Malic enzyme
- Isocitrate dehydrogenase The pentose phosphate pathway is particularly important, generating NADPH when glucose-6-phosphate is oxidized by glucose-6-phosphate dehydrogenase, and again when 6-phosphogluconate is oxidized by 6-phosphogluconate dehydrogenase.
Role of Serine Catabolism in Liver NADPH Production
A recent study published in Nature Metabolism 1 found that serine catabolism generates liver NADPH and supports hepatic lipogenesis. This study used stable isotope tracing in mice to show that de novo lipogenesis in adipose is supported by glucose and its catabolism via the pentose phosphate pathway to make NADPH, while the liver derives acetyl-CoA for lipogenesis from acetate and lactate, and NADPH from folate-mediated serine catabolism.
Clinical Implications
Understanding the role of NADPH in lipogenesis and the various pathways involved in its production is crucial for the development of therapeutic strategies aimed at modulating lipid metabolism. For example, inhibiting SHMT, a key enzyme involved in serine catabolism, may decrease hepatic lipogenesis, as shown in the study 1. This highlights the potential for tissue-specific pharmacological interventions targeting the pentose phosphate pathway and serine catabolism to modulate lipid metabolism and treat related disorders.