Insulin resistance and diabetes mellitus type 2 develop when there is an imbalance between conditions that promote excessive fatty acid synthesis combined with deficient fatty acid oxidation. The conditions mentioned are such things as dietary, genetic, hormonal, and exercise related areas. Of most concern in this paper, is the influence that genetic modifications may have on fatty acid metabolism. Much research has been done in this area, especially on the mouse, whose genome is considerably similar to the human genome. Through the study of the mouse genome, advances in human health, in the way of better insulin sensitivity, can be realized.
There are two main mouse models that illustrate which genes are involved most in fatty acid metabolism. The first model deals with mouse mutants used to study excessive and deficient fatty acid synthesis and oxidation. In regards to fatty acid/triacylgylcerol synthesis, sterol-response element binding protein over-expression can cause trigger an excess in these compounds. If one carries the diacylglycerol transferase -/- gene or the short-chain acyl coenzyme A dehydrogenase -/- gene, deficient level of fatty acid synthesis will occur. In regards to fatty acid oxidation, acetyl coenzyme A carboxylase 2 -/- gene or peroxisomal proliferator-activated receptor gene over-expression can result in a very high oxidation rate of fatty acids from the blood stream. If very longchain coenzyme A dehydrogenase -/- gene or long-chain acyl coenzyme A dehydrogenase -/- gene are part of one's genome, fatty acid oxidation in the body will be deficient.
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The second model deals with genetic manipulation of fatty acid metabolism. A wide range of manipulations have been performed and studied with varied phenotypic changes inflicted upon the mouses' body. For instance, targeting the null allele of Dgat or Acc-2 will result in the mouse being lean and resistant to obesity. This means that no matter what the mouse is fed, it will not gain a considerable amount of adipose tissue. On the other hand, targeting the null allele of Ppar will result in hyperlipidemia, insulin resistance, hepatic steatosis, decreased expression of fatty acid oxidation genes, and cold intolerance. These negative phenotypic changes in the mouse genetically predestine it to become obese.
Through the use of such models described above, researchers have been able to key in on the exact genes which can cause someone to have a propensity for insulin resistance, diabetes type 2, and obesity. But how can one relate nutritional considerations to genetic makeup? If someone has a certain defect/variant of one of the known causes for a negative phenotype, how can individualized nutrition help to blunt the effects of one's genotype.
It has been found that diets high in simple carbohydrates and low in fat are a huge risk factor in priming the body to make more fatty acids and not oxidize enough of them. The reasoning behind this is that this type of diet will drive insulin levels through the roof, causing the body to produce excess fatty acids. An even worse diet, which would be catastrophic for someone with an already unfavorable genotype, is the high carbohydrate and high fat diet. This diet not only spikes insulin levels up, it also provides excess fat to be stored by the body. So, if a person's genetic makeup favors fatty acid synthesis, then a high-fat, high-carbohydrate diet would increase the risk of developing insulin-resistance and diabetes mellitus type 2.
The control of insulin, through diet-mediated considerations, is paramount in protecting an already flawed genetic makeup. Insulin can be controlled by eating a diet that consists of higher protein and fat levels and lower carbohydrate levels. The carbohydrates consumed should not be high on the glycemic index, for this will drive insulin levels up.
Overall, the article keys in on the genetic factors that affect insulin resistance. Insulin resistance is the first step in a whole host of other problems, such as diabetes type 2 and obesity. Through the study of specific gene loci, genetic variations in such, and nutrigenomics, researchers have been able to acquire advanced knowledge about the prevention of insulin resistance. It was found that diets lower in carbohydrates and higher in fat/protein, for individuals with unfavorable genetic makeups are best for keeping insulin in an acceptable range. It is important to note that there are genetic variants in certain genes, such as the DGAT-1 -/-, which promote better health and give these people an advantage. When discussing such matters as personalized medicine, it will be interesting to see what certain people will do when they find out that they have a genetic makeup that allows them to eat anything they want, without having to worry about future medical conditions due to their poor choices of food.
-Wood, Philip. "Genetically modified mouse models for disorders of fatty acid metabolism: pursuing the nutrigenomics of insulin resistance and type 2 diabetes." Nutrition. Volume 20, Jan 2004, pgs. 121-126.
Genetic (DNA) Basis For Insulin Resistance, Diabetes - Treated With Specific Nutrition? STEATOSIS
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