Too much fat in the diet is associated with over weight and obesity. Besides consumption of too much fat is also responsible for a number of health disorders. When too much calories through fat are consumed , excess calories after meeting the needs of the body are stored in fatty tissues and the fat cells are embedded in an extracellular matrix made of connective tissues that provides support to them just like a scaffolding. Fat cells also excrete some important hormones like leptin into the same matrix.
One of such special proteins in the fatty tissues is Collagen VI and if too much of this protein is present in the extracellular matrix a situation may develop where the fat cells are not able to expand leading to inflammation. Deficiency of collagen enables the cells to assume huge sizes without causing any inflammation. Collagen VI, alpha 1 also known as COL 6 A1 is a human gene and it encodes a protein, alpha subunit of Type VI collagen chain. At high levels of Collagen VI can cause fibrosis and then severe inflammation which is contributory factor in metabolic disorders in humans. Inflammation leads to increased cell deaths and consequent systemic insulin resistance. Fat cells lacking in Collagen VI can grow to huge sizes without getting inflamed manifesting in apparent obesity though this is not considered unhealthy. The discovery of the role of Collagen VI in obesity in animal experiments may or may not have relevance to humans but if true it may explain the paradox, why all obese people, measured on BMI scale, are not always unhealthy. Such obese people, apparently enjoying good health, might be lacking in Collagen VI. What other consequences such huge fat cells will have on other body functions are not clear. It is a challenge to the scientists to confirm what is seen in animals as applicable to humans but it is certain that the COL 6 A1 gene in humans cannot be knocked out that easily. May be there is the possibility of inhibiting formation of Collagen VI in the body some way in future which can have a positive impact on human well-being.
There is also another situation when high intake of dietary fat is not manifested in developing obesity and according to some scientists, this probably involves the human gene Mgat 2 which finds expression in the formation of an important intestinal enzyme acyl: monoacylglycerol acyl transferase 2 (Mgat 2 enzyme), playing a role in fat absorption across the small intestine. The dietary fat which contributes almost one third of calories needed, is split into fatty acids and glycerol first by lipase and then recombined into triglyceride with the help of Mgat 2 enzyme for entry into blood stream. Again in animal studies Mgat 2 deficient subjects were found to be able to consume comparatively high amounts of fat without becoming obese or any other symptoms like glucose intolerance, hypercholesterolemia and fatty liver. This is interpreted to mean that lack of Mgat 2 reduces uptake of fat in the small intestine and delays its entry into the blood stream. Differences in Mgat 2 expression may contribute to the propensity of some people to gain weight from diets rich in fats while many others do not respond the same way. Inhibiting this particular enzyme may turn out to be an effective way to treat metabolic diseases that result from excessive fat consumption, at least theoretically since such a surmise presupposes that what emerged in animal studies is applicable to human beings also. Lot of home work needs to be done before coming to any definitive conclusion.
Findings vis-a-vis COL 6 A 1 and Mgat 2 open up two different potential routes for evolving remedial measures at the gene level against weight gain epidemic that is wide spread to day and redoubled efforts are called for in exploring them further in the coming years.