Dietary docosahexaenoic Acid (22:6) incorporates into cardiolipin at the expense of linoleic Acid (18:2): analysis and potential implications

Abstract

Cardiolipin is a signature phospholipid of major functional significance in mitochondria. In heart mitochondria the fatty acid composition of cardiolipin is commonly viewed as highly regulated due to its high levels of linoleic acid (18:2n - 6) and the dominant presence of a 4×18:2 molecular species. However, analysis of data from a comprehensive compilation of studies reporting changes in fatty acid composition of cardiolipin in heart and liver mitochondria in response to dietary fat shows that, in heart the accrual of 18:2 into cardiolipin conforms strongly to its dietary availability at up to 20% of total dietary fatty acid and thereafter is regulated. In liver, no dietary conformer trend is apparent for 18:2 with regulated lower levels across the dietary range for 18:2. When 18:2 and docosahexaenoic acid (22:6n - 3) are present in the same diet, 22:6 is incorporated into cardiolipin of heart and liver at the expense of 18:2 when 22:6 is up to ~20% and 10% of total dietary fatty acid respectively. Changes in fatty acid composition in response to dietary fat are also compared for the two other main mitochondrial phospholipids, phosphatidylcholine and phosphatidylethanolamine, and the potential consequences of replacement of 18:2 with 22:6 in cardiolipin are discussed.

Figure 1

The relative content of 18:1 and 18:2 of cardiolipin in heart and liver against their dietary levels. Values for heart are for rat (●) and those for liver are for rat and mice (○). For heart, a biphasic pattern of incorporation of 18:2 into CL was apparent (also present with mice values added) with a rapid initial conformer uptake between 2%–20% of dietary 18:2 and thereafter a relatively constant, regulated level. No biphasic trend was apparent for 18:1 in heart or 18:1 and 18:2 in liver. Data for heart came from the following studies [,,,,–,,–38,45,51] and that for liver from [15,24,33,35,40,41,52]. Diets with greater than 3% 22:6 or greater than 10% EPA were excluded from the analysis due to effects on 18:2 (see Figure 2) and conversion of 20:5 through to 22:6.

Figure 2

The relationship between the dietary availability of 22:6 and 18:2 and cardiolipin content of the same fatty acids in heart and liver of rat (●) and mice (○). Data for both organs indicate a biphasic relationship with CL 22:6 content increasing, and 18:2 content decreasing at dietary 22:6 levels between 0–20% and thereafter stabilizing. Data used included: control diet [36], sunflower oil and tuna oil [23], diet 1 and 4 [39], 4 month time point [45], high 18-3 diet, long chain n-3 diet [43], control, high 22:6 [33], soy oil and crocodile oil [41], sardine oil, corn oil [15], 18:2 and long chain n-3 [28].

Figure 3

The relative content of 18:1, 18:2 and 22:6 in phosphatidylcholine (PC) and phosphatidylethanolamine (PE) of heart and liver mitochondria against their respective level in the diet. Each figure includes both rat (●) and mouse (○) data. The incorporation of 18:2 into PE of both heart and liver show slight dietary conformity whereas 22:6 in both PC and PE of both heart and liver demonstrate strong dietary conformity throughout the dietary range examined. All other fatty acids in PC and PE of liver and heart demonstrated a relatively regulated content across the broad dietary range of fatty acids examined. Data used for heart PC was from [,,,,,,,,–41,43], for heart PE from [24,25,39,40], for liver PC from [15,24,26,31,33,40,41] and for liver PE from [15,24,26,31,33,40,41]. Data excluded from the analysis included diets that contained higher 20:5 than 22:6.