Genetic control of de novo lipogenesis: role in diet-induced obesity

Abstract

De novo lipogenesis (DNL) is a complex yet highly regulated metabolic pathway, and transcription factors such as liver X receptor (LXR), sterol regulatory element-binding protein-1c (SREBP-1c), and carbohydrate response element binding protein (ChREBP) exert significant control over the de novo synthesis of fatty acids. An increase in de novo lipogenesis (DNL) is an important contributor to increased fat mass, while a reduction in lipogenesis may be protective against the development of obesity. In this review, we explore fatty acid synthesis in the context of new insights gleaned from global and tissue-specific gene knockout mouse models of enzymes involved in fatty acid synthesis, namely acetyl-CoA carboxylase, fatty acid synthase, fatty acid elongase 6, and stearoyl-CoA desaturase 1. A disruption in fatty acid synthesis, induced by the deficiency of any one of these enzymes, affects lipid metabolism and in some cases may protect against obesity in a tissue and gene-specific manner, as discussed in detail in this review.

Keywords::

• de novo lipogenesis
• LXR
• SREBP-1c
• ChREBP
• acetyl-CoA carboxylase
• fatty acid synthase
• elongase 6
• stearoyl-CoA desaturase

Acknowledgments

We thank Mary Cantu for her assistance with design and production of Figures 1 and 3. We thank Laura Vanderploeg of the Media Center in the Department of Biochemistry, University of Wisconsin for assistance with design and production of Figure 2. We thank Dr. Matthew Flowers for critically reviewing this manuscript.

Declaration of interest

This work was supported by NIH grant R01DK-62388. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Editor: Michael M. Cox