Solinas Giovanni, Borén Jan, Dulloo Abdul G
Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Wallenberg Laboratory, University of Gothenburg, Gothenburg, Sweden.
Division of Physiology, Department of Medicine, University of Fribourg, Fribourg, Switzerland.
Mol Metab. 2015 Mar 20;4(5):367-77. doi: 10.1016/j.molmet.2015.03.004. eCollection 2015 May.
An acute surplus of carbohydrates, and other substrates, can be converted and safely stored as lipids in adipocytes via de novo lipogenesis (DNL). However, in obesity, a condition characterized by chronic positive energy balance, DNL in non-adipose tissues may lead to ectopic lipid accumulation leading to lipotoxicity and metabolic stress. Indeed, DNL is dynamically recruited in liver during the development of fatty liver disease, where DNL is an important source of lipids. Nonetheless, a number of evidences indicates that DNL is an inefficient road for calorie to lipid conversion and that DNL may play an important role in sustaining metabolic homeostasis.
In this manuscript, we discuss the role of DNL as source of lipids during obesity, the energetic efficiency of this pathway in converting extra calories to lipids, and the function of DNL as a pathway supporting metabolic homeostasis.
We conclude that inhibition of DNL in obese subjects, unless coupled with a correction of the chronic positive energy balance, may further promote lipotoxicity and metabolic stress. On the contrary, strategies aimed at specifically activating DNL in adipose tissue could support metabolic homeostasis in obese subjects by a number of mechanisms, which are discussed in this manuscript.
碳水化合物和其他底物的急性过剩可通过从头脂肪生成（DNL）转化并安全地储存为脂肪细胞中的脂质。然而，在肥胖这种以慢性正能量平衡为特征的情况下，非脂肪组织中的DNL可能导致异位脂质积累，进而导致脂毒性和代谢应激。事实上，在脂肪肝疾病发展过程中，肝脏中会动态募集DNL，其中DNL是脂质的重要来源。尽管如此，许多证据表明DNL是热量转化为脂质的低效途径，并且DNL可能在维持代谢稳态中发挥重要作用。
在本手稿中，我们讨论了DNL在肥胖期间作为脂质来源的作用、该途径将多余热量转化为脂质的能量效率，以及DNL作为支持代谢稳态途径的功能。
我们得出结论，在肥胖受试者中抑制DNL，除非同时纠正慢性正能量平衡，否则可能会进一步促进脂毒性和代谢应激。相反，旨在特异性激活脂肪组织中DNL的策略可通过多种机制支持肥胖受试者的代谢稳态，本手稿将对此进行讨论。
