Testdiet High Fat Diet Rats
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The Animal Model of Insulin Resistance Induced by High-fat Diet
1 2 2 Ma Bo-yan Song Ying-xing Li Yu-ting
(*Basic Medical College of Heilongjiang University of Chinese Medicine.
Graduate School of Heilongjiang University of Chinese Medicine.China.150040)
Abstract:
Background: Insulin resistance (IR) is the common morbidity basis of type 2 diabetes mellitus (T2DM), impaired glucose tolerance(IGT), hyperlipidemia, hyperuricemia, cardiovascular disease and metabolic syndrome . In lab studies, the establishment of animal model of insulin resistance is the primary condition, The modeling methods can be divided into four kinds: genotype, drug injection type, die3t induced type, various ways mixed. This article mainly discussesthe affection on the establishment of the model type which induced only by high fat diet in animal experiments.The influence conditions includes different high fat feed formula ratio, laboratory animal age, food intake and animal strains and so on.
Conclusion: The type with high fat calories, large food intake, old week ageis more likely to develop the insulin resistance model.
Keywords: High-fat Diet, Insulin Resistance (IR), Type 2 Diabetes Mellitus (T2DM), Animal Model
1 Background
Insulin resistance (IR) refers to a variety of reasons make insulin to promote glucose uptake and utilization efficiency decreased, the reactivity decreases insulin physiological function, i. e., impaired insulin to promote glucose uptake, compensatory insulin secretion grow in quantity, cause its important symbol for high insulin hematic disease [1]. Insulin resistance and its secondary metabolic disorder are the common morbidity basis of type 2 diabetes, low glucose tolerance, reduce, hyperlipidemia, high uric acid hematic disease, cardiovascular disease and metabolic syndrome. Studying on the experiment method is the major way in this field of research. In all animal experiments, insulin resistance model is the foundation and the prerequisite of research.
3 Ma Bo-yan: M.d., Ph.D.Associate professor,Master tutor
2 Song Ying-xing: Heilongjiang university of Chinese medicine graduate student level 2012
3 Funding for the project: The youth fund of national natural science fund (81102545)
There are many methods for setting up insulin resistance animal model ,the main ways are the genetic type, drug induced type, diet induced type and so on [2-5]. Here we mainly talk about the high-fat diet induced type in the diet inducible model. This way induces the formation of rats with insulin resistance by feeding the rats with high fat and high-calorie fodder simply , it becomes the most common used method in all kinds of experiments.
There are many reasons for human inducing insulin resistance,the unhealthy, high-calorie, high fat diet is one of the main risk factors [6]. The mechanism of insulin-resistance rats induced by high-fat dietis simulating unhealthy high fat diet of human, it embodies the factors such as environment, bad life habits, role in the pathogenesis of insulin resistance. The research found that chronic high fat diet, high caloric intake could easily induce obesity, affect the skeletal muscle cell membrane surface glucose transporter 4 (glucose from 4, GLUT4) protein expression, make ins4ulin stimulates GLUT4 transposition to the cell membrane, and affect the insulin signal transduction systemto promote the formation and development of insulin resistance [7]. And affect glucose stimulation of islet cell insulin secretion 4-6, and insulin resistance induced by high-fat diet in rats, the liver, adipose tissue of c-reactive protein (C - reactive protein, CRP) expression increased, while adiponectin expression of adipose tissue descends[8]. Another study found that chronic high fat feeding rats exists endothelial dependent vasodilation function decreases, its blood free fatty acid (FFA), free fatty acid and triglycerides (total triglyceride, TG) levels increased [9]. So the animal models of insulin resistance induced by high fat feed are stable and reliable, simple and practical, it mainly performs the characters of hyperglycemia, high weight, high insulin hematic disease.
2 The influencing factors of setting up models
There are a wide number of risk factors for causing insulin resistance, a little changes can cause great changes in the process of experiment,.Concerning the mechanism ofthe high-fat diet on rats with insulin resistance, the author makes the experiment observation and analysis. Comparingwith the similar experiments and other researchers,we find out that the differences of following factors can causethe similarities and differences of the successful time for building models and their qualities.
2.1 The composition of high fat diet and the aggregation of intake diet
High fat diet, as the name implies, its main difference of formula from ordinary ones is that fat accounts for different heat percentage. Fat divides into saturated fat and monounsaturated fat, different kinds of fat have different origins. Saturated fatty acids mostly exists in animal fat, fat accounts for heat ratio less than 30% in healthy diet. Currently the fat in rats' high-fat diet in the market are mostly lard [10-12], some is safflower oil [13]. In theory, the diet with higher content fat is easier to induce rats'insulin resistance, and also costsless time. Butthe highercontent of fat in the diet will lead to more difficulties in the production, processing, and preservation And with higher content of fat in the diet, the texture will be softer, this quality of diet does not conform to the rats'diet habits, so it influences the food intake of the rats easily decreasingthe independent food intake of rats to affect the total calorie intake of rats, it goes againstthe induce of insulin resistance.Although there are different high-fat forage varieties used for building models in the marketcurrently, but its fat calories in usually account for 40-65%, average feed fat calories often for 5-10%. For instance, the United States Research Diets company produces feed formulaas follows (table 1)
Compared with lots of experimental literatures, we can see that diets with different percentage of heat cost different building times . Tong Xing [14] feeds male Wistar rats of six weeks age with diet of 38. 5% fat and heat , there are no obvious differences between two groups until 12 weeks.Then he putsnewly acquired lard in the diet to change the fat calories percentage to 51. 3%.After feeding 4 weeks, weight, blood sugar data has appeared difference.The empty stomach blood sugar levels, fasting blood glucose, FBG) slight fluctuationsin the process of the experiment ,
but there is no significant differences between the two groups (P > 0.05). Fasting plasma insulin in high-fat group is 45. 7% higher than in control group (P < 0.01), and weight growth are significantly lower than the rats feeding with the diet which has 59% fat calories [15]. Wu Yanli [16]feeds the five or six weeks'old male rates weighting about 180 g with the high fat feed with56.0% fat and heat ,we can buildinsulin-resistance animal models with sugar tolerance by 12 weeks.The weight of model group was obviously higher than that of control group by the twelfth weekend, insulin and HOMA IR index is significantly higher than the control group. The above experiment suggests that the proportion of the high fat, high heat affected by the induction time of rats with insulin resistance. The intake of diet during the experimenthas some influences on the emergency of insulin resistance[17], the principle is likely the same as fat percentage of the high fat diet .The rats that restricted diet with less food intake will have less calories less. Conversely, the rats that independent diet will intake large total calories,so their time for models' building is short. ReimerM K etc.used high fat diet with 58% fat content foreating freely, he got the hyperinsulinemia in experimental groupin 8 weeks [18] . Domestic scholars use the same fat calories diet for feed freely, FBG significantly increasedat 4 weeks (P < 0.05), at 5 weeks FINS began to rise with no significant difference, triglycerides, total cholesterol, high-density lipoprotein cholesterol, low density lipoprotein cholesterol were all higherat 10 weeks (P < 0.01). HE staining showed moderate fatty liver. [19]. But under the same fat calories than the high fat feed, Gianluca Svegliati - Baroni, foreign researchers, restricted the rats'intake by each week according to the proportion between the saturated fatty acids and unsaturated fatty acids and rat weight , the rats'blood glucose, alanine aminotransferase and alanine aminotransferase, ALT) increased significantly until the 3 months (12weeks)[20]. The domestic scholars also find the body weight, blood sugar in the high fat group(divided into two groups, the feed fat calories than 45% and 60%, respectively)increased significantlythan the normal group (feed fat calories more than 10%)by contrast of different fat content of feed's influence on the metabolic syndrome in rats, But within the group, the diet with 60% fat calories has high fat content and they are soft which is unfavorable torats for eating, so this kind of feed affects the total calorie intake, so the blood sugar and weight of rats eating this kind of feed do not increase as significantly as the ones feeding with 45%fat calories. 45% of high fat feed for induced insulin resistance may be better than 60% of the high fat feed by overall consideration[21].
Table 1: Ordinary feed and high fat feed heatratio
High fat feed(D12451) Ordinary feed (D12450B)
Content(%) Energy ratio(%) Content(%) Energyratio(%)
Protein 24 20 19.2 20
Carbohydrates 41 35 67.3 70
Fat 24 45 4.3 10
Thefat calories in high fat feed is 45%, in ordinary feed is only 10% . It is not hard to seethat ordinary fat content in the feed is much lower than that in the high fat feed.
2.2 The initial weight and week ageofmodels
Week age of rats with insulin resistance is another influencing factor in the experiment,namely the week age of the rats used in initial experiment also has an impact on inducing insulin resistance. At the same fat calories than feed, Xu Lingling [22]feeds 14 weeks age SD rats with 270-320 - g weight ,the test group appear obvious insulin resistance at thesixtieth day , the 5/8 of the rat blood sugar value is higher than 8.3 tendency/l, and the control group has no greater than this value. Leptin and the seruminsulin levels of the test groupare significantly higher than that of the control group. BuShifeed 8 weeks old SD rats ,the fasting plasma free fatty acid (fasting free fatty acid, FFFA) of the experimental group rats was not significantly higher than the control group until16 weeks.
2.3 Strain
We use rats and micecommonly as insulin resistance models, the commonly used strains are Wistar rats, Sprague wrote Dawley (SD) rats and C57BL / 6 j mice, most of them are males. Wistar ratsaremeek and widely used,it has been widely used in all kinds of biological research experiments. SD rats are more fierce and its growth development periodsare long, weight of this kind gains faster than Wistar's ,Wistar rats have good resistance ability for infectious disease and developedendocrine system,so this king of rats are often used in endocrine experiment, Bai and other researchers feed SD rats with the high fat feed with 66.4%fat calories,the mRNA levels of ACC in rat skeletal muscle has increased gradually with the passage of time since the eighth week, but the serum insulin levels do not increase obviously with normal diet group [26]. In addition, C57BL / 6 j mice have ob/ob genetic background, being sensitive to the increasing high blood induced by fat, so this kind of rats are often used in the study of metabolic diseases [27]. Li Kang and other researchers feed C57BL / 6 j mice with 60% high fat diet for 20 weeks,then the rats appear hyperinsulinemia and mice models have inflammation of insulin resistance [28]. Therefore, we should choose suitable experimental animal strains when established the animal model of insulin resistance . Choosing different animal strains also have different effects on the result of the experiment.
3 Conclusion
In any animal tests, the establishment of test model is the first condition of experimentand the key to success. In the method of established animal model of insulin resistance, although the method of drugSTZinjection is rapid and practical, but this method impares experimental animals'insulin function greatly , it betrays the normal physiological function and is not easy to control [29].The high-fat diet induced method costs time reasonably, economical and practical, and it fits with the inducing environment of the human type 2 diabetes and insulin resistance, this modeling way is good for the combination of animal experiment and clinical application. Aftercomparison and analysis, we found that during the process of the establishment of experimental animals, strains, food intake, age or even high fat feed composition ratio, etc all can affect the process.By contrast,the animals with higher percentage of fat in diet, older week age and more quantity of intake heat are more likely to induce the insulin resistance. The Wistar rats and SD rats and C57BL / 6 j mice are commonly used model animals in experiments. The similarities and differences of the consuming modeling time and index quality in literature reported experiments can be affected by the above factors.
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Biophysical Characteristics of Meridians and Acupoints Commonly Used in the Reproductive System
LI Juan, 1 WANG Qing,1 LIANG Hui-ling,1 DONG Hao-xu,1 LI Yan,1 ERNEST Hung Yu Ng,2 WU
Xiao-ke 1
department of Obstetrics and Gynecology, National Key Discipline and Clinical Base, Heilongjiang University of Chinese Medicine, Harbin 150040, China Department of Obstetrics & Gynecology, The University of Hong Kong, Hong Kong Special Administrative Region, China
Abstract
Numerous experiments have demonstrated meridians and acupoints having many biophysical properties which include electric characteristics, thermal characteristics, acoustic characteristics, optical characteristics, magnetic characteristics, isotopic characteristics, and myoelectric characteristics. However, there is little evidence of the biophysical characteristics of meridians and acupoints commonly used in treating gynecological diseases. Therefore, we summarized these biophysical characteristics of meridians and acupoints commonly used in the reproductive system in this paper. The study implied that meridians and acupoints commonly used in treating gynecological diseases also have biophysical characteristics that are different from non-acupuncture points, and these properties are significant for gynecological effects. Owing to the limitations of previous studies, the application of biophysical characteristics of meridians and acupoints in various clinical specialties should be attention. And more experimental mechanistic studies and randomized controlled trials are warranted to further explore and evaluate the therapeutic mechanisms from the perspectives of the biophysical characteristics of meridians and acupoints.
Key Words : biophysical characteristic; meridian; acupoints; reproductive system
Acupuncture is an integral part of traditional Chinese medicine which dates back 3000-5000 years, and has become more established in Western medicine as a complement or alternative to conventional therapies. As a major part of acupuncture, meridian theory has guided clinical practice of acupuncture for thousands of years. Recently, researches on meridian essence have become core
issues. Numerous experiments have demonstrated meridians and acupoints having many
1 2
biophysical properties which are different from those of non-acupuncture points ' .The characteristics include electric characteristics, thermal characteristics, acoustic characteristics, optical characteristics, magnetic characteristics, isotopic characteristics, and myoelectric characteristics3.
The use of acupuncture within the area of reproductive endocrinology and infertility has gained increased popularity worldwide. Existing literatures shows that acupuncture is a suitable alternative or complement for inducting ovulation, adjusting endocrine and metabolic disorders, and used in vitro fertilization and embryo transfer without adverse side effects4,5.
However, there is little evidence of the biophysical basis of acupuncture in the reproductive system, such as biophysical characteristics of meridians and acupoints commonly used in treating gynecological diseases, and their applications in gynecology and obstetrics. Therefore, we searched
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