The enzymatic pathway for converting dietary carbohydrate (CHO) into fat, or de novo lipogenesis (DNL), is present in humans, whereas the capacity to convert fats into CHO does not exist. Here, the quantitative importance of DNL in humans is reviewed, focusing on the response to increased intake of dietary CHO. Eucaloric replacement of dietary fat by CHO does not induce hepatic DNL to any substantial degree. Similarly, addition of CHO to a mixed diet does not increase hepatic DNL to quantitatively important levels, as long as CHO energy intake remains less than total energy expenditure (TEE). Instead, dietary CHO replaces fat in the whole-body fuel mixture, even in the post-absorptive state. Body fat is thereby accrued, but the pathway of DNL is not traversed; instead, a coordinated set of metabolic adaptations, including resistance of hepatic glucose production to suppression by insulin, occurs that allows CHO oxidation to increase and match CHO intake. Only when CHO energy intake exceeds TEE does DNL in liver or adipose tissue contribute significantly to the whole-body energy economy.
It is concluded that DNL is not the pathway of first resort for added dietary CHO, in humans. Under most dietary conditions, the two major macronutrient energy sources (CHO and fat) are therefore not interconvertible currencies; CHO and fat have independent, though interacting, economies and independent regulation. The metabolic mechanisms and physiologic implications of the functional block between CHO and fat in humans are discussed, but require further investigation.
About this article
Cite this article
Hellerstein, M. De novo lipogenesis in humans: metabolic and regulatory aspects. Eur J Clin Nutr 53, s53–s65 (1999). https://doi.org/10.1038/sj.ejcn.1600744
Consumption of a diet high in dairy leads to higher 15:0 in cholesteryl esters of healthy people when compared to diets high in meat and grain
Nutrition, Metabolism and Cardiovascular Diseases (2020)
Nature Reviews Endocrinology (2020)
Serial Plasma Phospholipid Fatty Acids in the De Novo Lipogenesis Pathway and Total Mortality, Cause‐Specific Mortality, and Cardiovascular Diseases in the Cardiovascular Health Study
Journal of the American Heart Association (2019)
Journal of Parenteral and Enteral Nutrition (2019)
Hepatoprotective Effect of Kombucha Tea in Rodent Model of Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis
International Journal of Molecular Sciences (2019)