The roles of linoleic and alpha-linolenic acid, their oxylipins and the PPAR alpha-, delta and gamma-related peroxisomal pathways on obesity in the context of a “western” diet

Abstract

“Western”, Linoleic acid (LA) and refined carbohydrate calorie rich, Alpha Linolenic acid (ALA) deficient, nutrient depleted, highly oxidised inflammatory diets, combined with; lowered antioxidant capacity, heavily refined pre-oxidised food, and excess intake of easily oxidised sugars, amplifies natures signalling systems that trigger fat storage, putting fat deposition mechanisms into overdrive, leading to activation of oxidative stress related inflammation, and related adipose tissue macrophage immune signalling, so wider immune activation, mitochondrial dysfunction, insulin resistance, diabetes, metabolic syndrome and increased occurrence of comorbid “Western” diseases. Factors contributing to the risk of obesity are complex and multiple including; genetics; epigenetics; exercise; lifestyle; declining food quality; ability to sense combined with an inbuilt programming to hunger for, seek out and consume foods normally associated with a high nutrient content, namely plant reproductive tissue related foods that in nature are generally seasonal and are rich in; LA, sucrose, glucose, fructose, carbohydrates, antioxidants and minerals, but which in industrial-foods are often pre-oxidised, antioxidant depleted, and stripped during processing of their protective conutrients. In the context of a nutrient insufficient processed pre-oxidised Western diet, the consequence of high levels of the most common plasma LA oxylipins, the HODEs, and consequential activation of PPAR gamma related peroxisomal beta-oxidation pathways, is significant fat gain. LA oxylipins, the HODEs, are associated with a wide range of “Western” diseases in addition to obesity and diabetes. ALA equivalent but less researched oxylipins are in general protective. ALA followed by LA is the preferred substrate of LOX12/15, which in the absence of the competitive presence of ALA will produce LA HODEs. Further two oxidised Omega-6 AA products activate CB1 cannabinoid receptors, helping drive hunger and fat deposition. Mechanisms that may increase hunger also exist for the plant reproductive material related products fructose and glucose. Activation by inter-meal fasting, and or exercise, of PPAR alpha peroxisomal beta oxidation pathways is obesity protective, through activation of energy production pathways, increased antioxidant capacity, and diversion of inflammatory related LA peroxisomal beta-oxidation substrate to energy rather than repair, but not options chosen by many in a “Western” 24/7/365 culture of instant, cheap, highly refined, pre-oxidised LA rich food availability. Moderating LA intake, increased ALA intake, and intermittent energy deficit stress through exercise or short term fasting, combined with a nutrient dense diet, high in antioxidants and low in pre-oxidised products, particularly in the obese, may reduce inflammation, and oxidative stress, hence direct a greater balance of resources towards energy production rather than tissue repair and fat depostion pathways, and reduce mitochondrial damage and dysfunction, so limit adipose tissue gain and comorbid medical conditions, as evidenced in the use of intermittent short term fasting treatment in diabetes. Exercise without dietary change or calorie restriction, is not an automatic route to weight loss.