The Mediterranean diet: effects on proteins that mediate fatty acid metabolism in the colon

Abstract

A Mediterranean diet appears to have health benefits in many domains of human health, mediated perhaps by its anti-inflammatory effects. Metabolism of fatty acids and subsequent eicosanoid production is a key mechanism by which a Mediterranean diet can exert anti-inflammatory effects. Both dietary fatty acids and fatty acid metabolism determine fatty acid availability for cyclooxygenase- and lipoxygenase-dependent production of eicosanoids, namely prostaglandins and leukotrienes. In dietary intervention studies and in observational studies of the Mediterranean diet, blood levels of fatty acids do reflect dietary intakes but are attenuated. Small differences in fatty acid levels, however, appear to be important, especially when exposures occur over long periods of time. This review summarizes how fat intakes from a Greek-style Mediterranean diet can be expected to affect fatty acid metabolizing proteins, with an emphasis on the metabolic pathways that lead to the formation of proinflammatory eicosanoids. The proteins involved in these pathways are ripe for investigation using proteomic approaches and may be targets for colon cancer prevention.

Figure 1. Metabolism of dietary fatty acids to eicosanoids

Metabolic processes modulate the effect of dietary changes on fatty acid levels in membranes and on the eicosanoids that are formed.

Figure 2. Formation of eicosanoids: select products

The other products shown are from n-6 fatty acids except for PGE3 and LTB5, which are formed from n-3 fatty acids. Eicosapentaenoic acid inhibits oxygenation of arachidonic acid by cyclooxygenase 1 (COX-1), but this inhibition is modest with COX-2. The n-9 fatty acid oleic acid (18:1, n-9) forms 20:3 (n-9), which has not been studied as extensively (not shown), but it has been reported to form the unstable LTA3 via 5-lipoxygenase that, in turn, inhibits formation of LTB4.^,