Acylation-stimulating Protein (ASP) Deficiency Induces Obesity Resistance and Increased Energy Expenditure in ob/obMice*
Here is where dietary fat leading to obesity seems to come into play. I consider it indisputable fact at this point that accumulation of fat in adipose tissue has far less to do with insulin "trapping" fatty acids in than it has to do with ASP-mediated sequestering of triglycerides into adipose tissue. I encourage any new readers to start here.
Basically, dietary fat is transported from the intestines to fat tissue as chylomicrons. Chylo stimulate ASP (and are the major stimulator of ASP action, insulin does have an effect but many fold lower). ASP stimulates both glucose transporters and the esterification of free fatty acids. ASP's role is to clear dietary fat from the bloodstream. The "energy" form of fats is free fatty acids (NEFA/FFA) and levels of this are controlled through inhibition of release from adipose tissue by insulin.
The whole excess carb is transported into fat cells by insulin and converted to fat theory of obesity has also pretty much been dispelled as a major contributor in humans. (Check out my DNL posts)
OK, so what of this study? Here's the abstract:
Acylation-stimulating protein (ASP) acts as a paracrine signal to increase triglyceride synthesis in adipocytes. ASP administration results in more rapid postprandial lipid clearance. In mice, C3 (the precursor to ASP) knockout results in ASP deficiency and leads to reduced body fat and leptin levels. The protective potential of ASP deficiency against obesity and involvement of the leptin pathway were examined inC3(−/−) double knockout mice (2KO). Compared with age-matched mice, 2KO mice had delayed postprandial triglyceride and fatty acid clearance; associated with decreased body weight (4–17 weeks age: male: −13.7%, female: −20.6%, < 0.0001) and HOMA (homeostasis model assessment) index (−37.7%), suggesting increased insulin sensitivity. By contrast, food intake in 2KO mice was +9.1% higher over mice ( < 0.001, 2KO 5.1 ± 0.2 g/day, 4.5 ± 0.2 g/day, wild type 2.6 ± 0.1 g/day). The hyperphagia/leanness was balanced by a 28.5% increase in energy expenditure (oxygen consumption: 2KO, 131 ± 8.9 ml/h; 102 ± 4.5 ml/h; < 0.01; wild type, 144 ± 8.9 ml/h). These results suggest that the ASP regulation of energy storage may influence energy expenditure and dynamic metabolic balance.
Do these mice violate the first law of thermo or caloric balance? Apparently no! Their reduced ability to sequester dietary fats into adipose tssue is countered by an almost 30% up-tick in energy expenditure. This is probably the futile cycling seen in rodent models (that is not seen at the same magnitude in humans). A reasonable mechanism would be that the mouse body's think the mouse has drastically overfed itself due to higher circulating triglycerides upregulating the futile cycles to waste excesses. But at the same time, since the fat cells aren't adding the usual excesses of triglycerides to its fat tissue, leptin is not secreted at usual levels. Leptin should tamp appetite, thus decreased amounts would account for the almost 10% increase in caloric intake.
I do not know what this all means in the scheme of things for development of human obesity, but it at least seems plausible that this may be the mechanism by which high fat -- in a hypercaloric SAD context -- diets induce obesity. In humans, a high fat diet does increase fatty acid oxidation but this is a delayed (days/weeks) adaptation rather than the immediate stimulatory effect as seen for carbs and amino acids.