De novo lipogenesis in humans: metabolic and regulatory aspects

The enzymatic pathway for converting dietary carbohydrate (CHO) into fat, o r 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 he patic DNL to any substantial degree. Similarly, addition of CHO to a mixed diet does nor increase hepatic DNL to quantitatively important levels, as l ong as CHO energy intake remains less than total energy expenditure (TEE). Instead, dietary CHO replaces fat in the whole-body fuel mixture, even in t he post-absorptive state. Body fat is thereby accrued, but the pathway of D NL is not traversed; instead, a coordinated set of metabolic adaptations, i ncluding resistance of hepatic glucose production to suppression by insulin , occurs that allows CHO oxidation to increase and match CHO intake. Only w hen CHO energy intake exceeds TEE does DNL in liver or adipose tissue contr ibute significantly to the whole-body energy economy. It is concluded that DNL is not the pathway of first resort for added dieta ry CHO, in humans. Under most dietary conditions, the two major macronutrie nt energy sources (CHO and fat) are therefore nor interconvertible currenci es; CHO and fat have independent, though interacting, economies and indepen dent regulation. The metabolic mechanisms and physiologic implications of t he functional block between CHO and far in humans are discussed, but requir e further investigation.