as both the precursor and nuclear forms of SREBP1c. Because SREBP1c is a key factor in the transcription of several lipogenic genes, its decline leads to a reduction in lipogenic gene expression and de novo lipogenesis.

Clearly, fatty acid effects on cell function go far beyond serving as sources of energy and structural components of membranes. Fatty acids enter cells, undergo metabolism, and can serve as ligands for both membrane and nuclear receptors. Alternatively, fatty acids or their metabolites can regulate the nuclear abundance of SREBP1c, a key transcription factor in the synthesis of fatty acids and triacylglycerols.

SUMMARY

I have highlighted some of the recent advances in macronutrient regulation of gene expression, and I have provided the detail needed to understand the roles and effects of these nutrients. In addition to their role as an energy source, as structure elements or precursors to signaling molecules, macronutrients clearly have profound effects on gene expression. This nutrient-genome interaction interfaces with other signaling networks to allow integration of cellular control between dietary intake and internal regulatory mechanisms. It reflects an adaptive response, allowing cells to adjust to changes in the type, quantity, and duration of nutrients ingested for efficient growth.

While pharmacologic agents have been developed to control cholesterol synthesis (i.e., statins) and lipid synthesis (i.e., fibrates or thiazolidinediones), a better understanding of these regulatory processes will allow for the design of more effective agents to modify metabolism in both man and animals. This understanding and ability to design agents to modify metabolism will have benefit to human health, as well as animal production and health.

REFERENCES

Brown, M.S., and J.L. Goldstein. 1997. The SREBP pathway: Regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell 89: 331-340.


Jump, D.B., and S.D. Clarke. 1999. Regulation of gene expression by dietary fat. Annu. Rev. Nutr. 19: 63-90.



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