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Diet- Induced Metabolic Syndrome

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Diet- Induced Metabolic Syndrome in Rodent Models- ALN Magazine March 2007

by Angela M. Gajda, MS, Senior Scientist, Research Diets, Inc.
Michael A. Pellizzon, Ph.D. Senior Scientist, Research Diets, Inc.
Matthew R. Ricci, Ph.D., VP, Science Director, Research Diets, Inc.
Edward A. Ulman, Ph.D., President, Research Diets, Inc.

A discussion of how diets made from purified ingredients influence the phenotypes of the MS in commonly used rodent models.

A quick look at a crowd of people shows that many of our fellow humans are carrying around too much excess weight. The prevalence of obesity is at epidemic levels in the developed world, and obesity may be the root cause of or precursor to other diseases such as insulin resistance, abnormal blood lipid levels (hypertriglyceridemia and reduced high density lipoprotein cholesterol), and hypertension (high blood pressure). The term ‘metabolic syndrome’ (MS) is used to describe the simultaneous occurrence of these diseases and people with the MS are at increased risk for type 2 diabetes, cardiovascular disease, cancer, and nonalcoholic fatty liver disease. It is estimated that individuals with the MS spend over $4000 per year in treatment and to make matters worse, the prevalence of the MS is growing at an alarming rate, even in obese children.

Genes and Environment
Like many diseases, the risk of developing the MS will depend upon the interaction of one’s genes and their environment. Since the genetic make-up, or genotype of the human population has not changed over the past several decades, we must look to the environment as the main cause of the increase in metabolic disease during this time frame. Since the
genetic make-up, or
 


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Click Here for Literature References

 
 
 

genotype of the human population has not changed over the past several decades, we must look to the environment as the main cause of the increase in metabolic disease during this time frame. To be sure, decreased daily physical exercise (and fewer calories expended) plays an important causal role. Research has shown that increased exercise can ameliorate or even reverse the progression of diseases that make up the MS.

Diet
On the other side of the energy balance equation is the food that we eat. From an evolutionary point of view, it has been argued that obesity and other ‘diseases of excess’ are in fact the natural outcome of eating too many calories. During the evolutionary process, because the food supply was not stable and periods of starvation were common, it was advantageous to have genes that allowed for the efficient storage of excess calories as fat, given the uncertainty of when the next meal would come. In our present society, the problem is that we still have those ‘thrifty genes’ but also have a variety of foods that are high in saturated fat, simple sugars, and salt. Unfortunately for us, many of these foods are inexpensive and highly accessible (not to mention very tasty), and we find them easy to consume in excess, leading to disease and most likely early death. On the flip side of caloric intake coin is the very interesting finding that long-term restriction of calories prolongs the lifespan. (1) This concept that nutrients can change our biology or phenotype, called nutriphenomics, is very important and brings together many disciplines — physiology, endocrinology, and molecular biology to name a few — in the pursuit of how the nutrients we eat can affect biological outcomes.

            Fig. 1
Overlapping Risk
Factors Define the
Metabolic Syndrome
       

Animal Models
The costs of treating the MS are clearly growing, and it is no surprise that the research community is seeking animal models that mimic the human phenotype so that potential therapies can be tested. Because of the pivotal role that diet plays in causing the MS in humans, most metabolic disease animal models do (and we believe should) use diet as a way to precipitate this syndrome. Though this was not the case decades ago, today, most diet-driven animal disease models are generated using open source, purified ingredient diets. The open source nature of purified ingredient diets allows researchers around the world to compare data from different studies, since the diet formulas are generally freely available to the public (this is in contrast to chow diets, which are generally ‘closed,’ meaning the formulas are generally kept secret). In addition, purified ingredient diets have very little variability from batch to batch (compared to chows), and so help to minimize data variability. Since the ingredients used are so highly refined, purified diets lack the hundreds of plantderived phytochemicals that are found in grain-based chow diets. Some of these compounds, in particular the phytoestrogens, are known to affect disease progression (2) and so are usually unwanted variables. Finally, purified ingredient diet formulas can be easily modified so that researchers can intentionally and specifically change one ingredient at a time, allowing them to study the effects of large or small changes in the nutritional quantity and quality of the diet. Because of these advantages (being able to report, repeat, and revise the diets), most metabolic disease animal research uses (and in fact requires) purified ingredient diets. For an expanded discussion of diets, see our previous article in this publication. (3) In this brief review, we discuss how diets made from purified ingredients influence the phenotypes of the MS in commonly used rodent models. (For complete text click here.)

Reference List
1. McCay, C. M., Crowell, M. F., and Maynard, L. A. The effect of retarded growth upon the length of the life-span and ultimate body size. J.Nutr. 10, 63-79. 1935.
2. Thigpen,JE, Setchell,KD, Saunders,HE, Haseman,JK, Grant,MG, Forsythe,DB: Selecting the appropriate rodent diet for endocrine disruptor research and testing studies. ILAR.J 45:401-416, 2004
3. Ricci, M. R. and Ulman, E. A. Laboratory Animal Diets: A Critical Part of Your In Vivo Research. Animal Lab News 4(6). September/October 2005
     
                 
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