The dual Lipidoxidation

Fatty acids (FA) are the preferred form of energy storage in the human body. Adipose tissue contains large amounts of FA stored as the esterified lipid in the form of triglycerides (TG). Adipose tissue TG accumulates when there is excess lipid energy circulating in the blood stream either as fatty acids (FFA) or as lipoprotein-bound TG. In times of energy need induced by muscular activity adipose tissue TG stores will be slowly emptied through TG hydrolysis and subsequent release of FFA into the blood stream. The energy contained in FA is then used mainly by muscle free by “burning the fat” ( ß-oxidation of FA in the mitochondria of muscle cells ). In the resting state without increased energy need ,however, FA are only partly removed by resting muscle, while the liver is now taking on a central metabolic role by taking up large amounts of the FA released from adipose tissue in order to satisfy its own energy need. The mitochondrial ß-oxidation system of the liver is now increasingly “burning the fat” released from adipose tissue. In times of  continuous energy deficit ,i.e. in starvation , the mitochondria both of muscle cells and of liver cells are jointly releasing FA energy through lipid oxidation.
In obesity and the metabolic syndrome , however, the excess FAs stored in adipose tissue are constantly “inundating” the body, while the inactive muscular compartment is not removing enough of the circulating FFA. Thus, the liver is faced with an enormous FA burden to be taken care of day and night. As its energy requirements  are already met, the liver is now re-exporting part of its FA load incorporated into lipoprotein triglycerides (TG in Very Low Density Lipoproteins ,VLDL). This process leads the unused FAs originally released from adipose tissue stores back to their very origin there, thus creating a “vicious cycle” with no energy lost at all as the result. Hence, the key question in the treatment of overweight and obesity is how to “burn body fat” without the need for constant and intensive activation of muscular activity, which is well known to require a very high level of motivation for physical activity not easily attainable for an obese individual. If it were possible to stimulate the hepatic FA oxidation machinery to such an extent that it could replace at least part of the FA oxidation capacity of the muscular activity lacking in obesity, then weight loss by “burning the fat” might be achievable without the absolute requirement for such a strenuous and demanding exercise program.
In terms of fundamental cell biology the liver cell appears to be well equipped with a very high capacity and  throughput system for FA oxidation. It disposes of two independent but interacting systems of FA oxidation: the mitochondrial and the peroxisomal system. While the mitochondrial system mainly processes  medium and relatively short long chain FAs, very long chain unsaturated FAs ( >18- 20 C atoms chain length) are degraded mainly by the peroxisomal system, which is part of the microsomal “detoxification apparatus” of the liver . Apparently, these two systems cooperate in as far as the peroxisomal system first cuts the very long chain FAs down to a chain length of 10-12 C atoms. The further breakdown of thus generated medium chain FAs is then accomplished by the microsomal system. Regarding a therapeutic approach to an optimized FA oxidation system of the liver it would seem obvious to separately stimulate the two FA oxidation systems in order to maximize their cooperativity.
The natural way to accomplish this would be to cause gene induction of the respective enzymatic cascades by offering a very high concentration of the respective substrate FAs.
As has been shown by experiments on the cellular and sub-cellular level the ideal substrate for gene induction of the mitochondrial FA oxidation system are medium chain FA ( C-8 (Octanoate) and C-10 Decanoate). The peroxisomal FA oxidation system is optimally induced by very long chain omega-3 FA ( Eicosapentaenoate (EPA) and Docosahexaenoate (DHA).
There is no fat of animal or plant origin containing very large amounts of
medium chain FAs and of omega-3 FAs combined as the main fat components ready for activation of the dual lipid oxidation process in the liver. High concentrations of medium chain triglycerides (MCT) are found in two tropical oils,i.e. coconut oil and palm kernel oil, while omega-3 FA are predominantly contained in fish oil from fish caught in very cold sea waters near the two arctic circles .One would have to create an unlikely fusion of a typical, exclusively cold water fish based diet of a Greenland Eskimo enriched with omega-3 FA with that of a traditional Polynesian cuisine rich in coconut oil as the source of MCT in order to achieve some of this FA oxidation effect in the liver.
The combination of high concentrations of MCT ( 40% of total calories) and omega-3 FA (8%)as the main fat component integrated into a low carbohydrate (30 % ) and high protein (20%) liquid formula diet was shown to have major impacts on human FA metabolism .
Such a liquid formula given in isocaloric amounts as the only source of fat decreased the concentrations of most circulating FAs, especially of linoleic acid (the main omega-6 FA) within plasma cholesterol esters within a few days of application. In parallel to this dramatic decrease in omega-6 FAs the omega-3 FAs EPA and DHA showed a dramatic rise in plasma cholesterol esters and phospholipids, respectively. The omega-3 / omega-6 FA ratio in plasma changed from a range of 0.2 typical for Western populations to an inverse ratio of 1.75 , which is even higher than the one found in Greenland Eskimos ( ~ 1.0 ).
The plasma omega-3/omega-6 ratio is the main predictor of inflammatory activity response of an individual, because linoleic acid is the precursor molecule of intensely pro-inflammatory
omega-6 derived eicosanoids, while the omega-3 FA EPA is very effectively reducing the inflammatory activity of the body. Therefore , a high plasma concentration of omega-3 FAs has a high therapeutic efficiency and efficacy in a number of disease processes with significant inflammatory activity ,such as rheumatoid arthritis, inflammatory skin diseases , inflammatory bowl disease ,obstructive lung disease, asthma and cardiovascular disease (atherosclerosis). In coronary heart disease (CHD) omega-3 FAs also showed anti-arrhythmic properties leading to a reduced incidence of sudden cardiac death in large clinical studies .
Therefore , the intake of omega-3 FA preparations has been recommended world wide for patients with CHD.
Even a short term application of the MCT/omega-3 FA formula for less than a week already showed a very effective reduction of circulating plasma TG – rich lipoproteins, both of hepatic (VLDL) as well as of intestinal origin (chylomicrons and remnant lipoproteins). At the same time HDL cholesterol increased significantly, while there are only minor effects on LDL cholesterol. This TG-lowering action of the MCT/omega-3 formula appears very paradoxical at first glance, because it is achieved by employing a fat-rich source of nutrition.
The remarkable weight loss achievable by an extended application of the formula over several weeks appears even more paradoxical, because a fat-rich diet is normally associated with a gain and not with a loss of fat mass in the human. However, as mentioned above, the activation of the dual lipid oxidation system of the liver significantly reduces the circulating FAs released from adipose tissue. This reduction is achieved without activation of muscular activity, i.e. it is entirely due to the dual lipid oxidation system activation. Because of its fat-rich property the MCT/omega-3 formula is causing a feeling of satiety due to feedback of the upper GI tract to the brain via nervous and hormonal stimuli. This satiety effect makes weight loss without the feeling of hunger possible. Apparently, the long term use of a small amount of the fat-rich MCT/omega-3 formula over several months helps to maintain the weight loss for extended periods of time, thereby counteracting the expected weight cycling so typical for obesity. In patients with impaired glucose tolerance and type II diabetes the reduction of circulating FFAs by the formula significantly improves insulin sensitivity and control of hyperglycemia. (Translation of the article from "lipid news")