The process of DNL has gained more and more attention over the last few years, and it seems that the enzymatic pathways involved are not only interesting targets for obesity therapy (Abu-Elheiga et al. 2001, 2003; Kuhajda et al. 2005) but also for the treatment of other diseases such as cancer (Kuhajda et al. 2000). Modern transgenic animal technology allowing inducible gain-of-function and loss-of-function manipulations of a target gene in a specific organ will help to better understand the role of DNL in energy homeostasis. Organ-specific interference with enzymes of the DNL pathway for the treatment of obesity is presumably necessary because DNL seems to be important for normal embryonic development, especially of the brain (Beigneux et al. 2004).
Currently, several different food ingredients are being screened that inhibit DNL, or more precisely FAS, such as protein concentrates from Amaranthus cruentus seeds (Escudero et al. 2006) and whey protein (Morifuji et al. 2005). However, only animal studies are available so far, and whether these substances are useful supplements for humans is not clear yet. In general, it has to be considered that inhibition of FAS entails an increase in cytosolic malonyl-CoA levels, causing inhibition of CPT 1 and consequently of mitochondrial fatty acid oxidation. Short-term inhibition of fatty acid oxidation improves hyperglycemia (Deems et al. 1998), but long-term inhibition causes accumulation of TAG in liver and muscle and reduces insulin sensitivity (Dobbins et al. 2001).
In summary, all substances discussed in this review have been shown to suppress DNL, but their efficacy to cause weight loss is less clear and also the safety of long-term therapeutic use of some of these substances appears questionable. Consequently, the use of these substances can only be recommended with caution. Further screening of food ingredients that interfere with the enzymes of DNL might lead to the discovery of supplements that have a high efficacy and are safe.
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