On the role of stearoyl-CoA desaturase-1 and oleic acid in metabolism
Dear reader,
The article published recently by the group of Ntambi in Cell Metabolism, December issue 2007, underlines the metabolic key role of oleic acid that is generated from stearic acid through action of stearoyl-CoA desaturase-1 (SCD1); it is concluded that this molecular species modulates adipogenesis and gluconeogenesis [1]. Deficiency of this enzyme, in global or liver-specific knock-out mice models, in fact protects from obesity and insulin resistance. The relevance of oleic acid produced through this enzyme in the control of lipid metabolism and insulin sensitivity is also stressed in the review published in this issue of EJLST by Dobrzyn et al. [2]. The core message of these articles is that an overproduction of oleic acid through SCD1 and an enhanced availability of this fatty acid contribute to dysregulation of lipid and carbohydrate metabolism.
I shall consider first the unique features of oleic acid (OA) per se that contribute to its biological roles:
2 OA is generally the most abundant fatty acid in organisms and biological systems (including plants and insects), indicating that it can be easily synthesized and stored.
2 A more active incorporation of a fatty acid into a specific glycerolipid class in general will result in elevation of the levels of both the fatty acid and of the specific lipid class. For instance, enhanced synthesis of phosphatidylserine in neuronal cells is caused by enhanced availability (supplementation) of docosahexaenoic acid, a fatty acid particularly abundant in this phospholipid class and highly concentrated in neurons [3].
2 In the case of OA this fatty acid appears also to be the most abundant in triacylglycerols, a lipid class in which it is also preferentially incorporated in comparison to other lipid classes (phospholipids and cholesterol esters), at least in plasma and red blood cells [4].
2 In addition, due to its physico-chemical features, i.e. having a transition temperature of about 147C, OA is the most relevant intermediate between saturated fatty acids and polyunsaturated fatty acids and is best fitted for being stored or incorporated in most biological systems (in relation to environmental conditions), and to modulate basic features in biomembranes.
2 OA is mainly esterified in the sn-2 position of neutral glycerolipids, a position whose constituents undergo a more active turnover than those at positions sn-1 and -3. This implies that availability of OA facilitates its esterification into lipids (e.g. into triacylglycerols of adipocytes).
2 Most saturated fatty acids and particularly stearic acid, the metabolic precursor of oleic acid, are mainly esterified in sn-1 and -3 positions of neutral glycerolipids, positions whose constituents are metabolically more stable and undergo slow turnover. In glycerophospholipids, highest levels of saturated fatty acids, especially stearic acid in plasma and cells, are found in fact in the stable sn-1 position.
2 Higher proportions of OA at the expense of polyunsaturated fatty acids occur therefore mainly at the sn-2 position and are associated to limited changes of stearic acid. This results in elevation of the stearic acid / oleic acid ratio that is considered an index of SCD1 activity. Yet, it may also indicate preferential esterification of OA over stearic acid into a more easily synthesizable lipid pool, especially into acceptor triacylglycerols. Both availability of a given fatty acid and its specific esterification into neutral and complex lipids dictate its accumulation in cells and tissues.
2 Moreover, OA undergoes rapid transport across plasma membranes of adipocytes [5], a process that facilitates translocation of fatty acids into cells of adipose tissue. All this leads to facilitated deposition of OA in triacylglycerols.
Secondly, some uncertainties emerge for the evaluation of the data reported in the paper referred to above [1]. As data on daily intakes of OA through the diets in the various groups of