In a western dietary context excess oxidised linoleic acid of dietary and endogenous origin by over-activation of ppar gamma so immune and inflammatory pathways, and through cardiolipin damage, increases cardiovascular risk

Abstract

The heart, an organ with high ATP requirements, derives 70% of its energy from fats, primarily delivered by LDL in the fasted state and chylomicrons in the fed state. The primary “cause” of cardiovascular disease is not pure dietary “saturated” fats per se, although excessively oxidised linoleic acid (LA)-rich non-ruminant animal so-called “saturated” fats may well be significant factors, but is arguably due to a mixture of: excess Omega 6 LA intake within the context of a nutrient including antioxidant depleted pre-oxidised western diet, raised plasma oxidative stress including of LDL, damage to cardiolipin species and consequent release of LA oxylipins including 9- and 13-HODE 4-HNE and MDA so increased oxidised stress, consequential and wider oxidative stress related damage to mitochondria including their DNA, hence reduction in cardiac mitochondrial energy output; excess LA oxylipins of dietary and endogenous origin leading to consequent overactivation of oxidised LDL receptors and PPAR gamma pathways, so excess inflammation and immune activation including of iNOS hence raised peroxisomal peroxide-related oxidative stress; PPAR gamma activation by LA HODEs including 9 and 13 HODE and resultant PPAR gamma-related shunting of peroxisomal beta-oxidation product ACoA to lipid and cholesterol production and deposition rather than mitochondrial energy substrate production; and lack of PPAR alpha activation through exercise, fasting, or to a lesser extent by omega 3s, of mitochondrial energy substrate production-related pathways, combined with consequent damage to cell tissue as well as mitochondria, so energy inhibition and resultant malfunction including; inflammation, tissue destruction, and macrophage foam cell related and wider intra and inter-cellular lipid deposition; all facilitated by pre-oxidised excessively refined nutrient and antioxidant depleted, AGE and cross-linked protein, oxidised lipid product-rich, LA ALA-imbalanced, “Western” diets, combined with constant food accessibility, exacerbated by lack of intermeal “fasting” and energy expenditure including exercise.