| There were two different adipose tissues in animals, white adipose tissues and brown adipose tissues. White adipose tissue was mainly stored in the form of triglyceride. Brown adipose tissue was a very specialized thermogenic origans,which through mitochondrial uncoupling protein-1 fatty acid oxidation and ATP producing uncoupling, the direct energy in the form of heat dissipation. With the deepening of the study, cold induced which produce Beige fat cells of a brown-like in white adipose tissue and the changes known as “browning”. These kinds of cells are rich in mitochondria, and the express BAT specific heat producing gene- UCP1. Therefore the activation of BAT, inducing beige fat cells, fat consumption to produce heat,increasing energy expenditure, have very important obesity resistance. The tree shrew(Tupaia belangeri) as the research object, respectively studied adipose tissues from the physiological basis, PEP/CT scanning, adipose tissue morphological study and flow cytometry of the tree shrew under cold acclimation. We not only establish the tree shrew as test animal obesity model and provide a variety of new test methods and basic data, but also to BAT for target organ for treatment of human obesity and other metabolic diseases provide an ecophysiological basis.This paper is mainly divided into the following four parts:(1) Effect of cold acclimation on body mass, adipose tissue mass, UCP1 content,blood physiological and biochemical indexes in tree shrew: during the cold, body mass, “typical” WAT mass and content, the “typical” BAT mass and content and UCP1 content increased significantly of tree shrews. A large amount of white fat mass in the body is mainly caused by the increase in body mass. And through the “typical”BAT content and UCP1 content increasing, the tree shrews increased heat production in response to cold stress. Changes of physiological and biochemical indexes of blood:cold acclimation groups of tree shrews commonly used blood routine index of white blood cell, hemoglobin, red blood cell, platelet showed no significant differences compared with that of the control groups. Cold acclimation group of blood biochemical glucose, aspartate aminotransferase were significantly higher than that ofthe control group, alanine aminotransferase(ALT), glutamine transferase were significantly lower than that of the control group. The tree shrews under cold acclimation increased blood glucose, by increasing energy intake and heat production to maintain the body’s energy balance resistance to cold stress. And perhaps it is due to a large number of high energy food intake, increased the metabolic burden of liver in tree shrews. The liver metabolism function produced adverse effects.(2) Studies of PET / CT scan imagings of tree shrew under cold acclimation: the first use of PET / CT has carried on the discussion to the Tupaia belangeri metabolic activities of adipose tissue, and through the different drug concentration gradient experiments we first successfully acquire the best injection concentration 110-160μCi in tree shrew, this can obtain the most effective tracer radiation values.With cold acclimation time prolonged, PET/CT scan imaging in brown adipose tissue on day 0, 28, 49 showed significant differences in tree shrew. The average SUV value of the neck, shoulder blade, armpit and other “typical” BAT were significantly different from that of the control group, and increased by 10.4 times, 9.8 times and13.65 times compared with the control group at 49 d, respectively. Results showed that during the cold acclimation, tree shrews by enhanced BAT thermogenic activity to improve the heat production.Inguinal, abdominal greater omentum, mesentery “typical” wat mean SUV values in 28 d of cold acclimation group of tree shrew had significant difference compared with that of control group, which increased by 5.5 times, 2.56 times, 5.17 times compared with the control group at 49 d. It showsed that cold acclimation in the tree shrew “typical” WAT increased 18F-FDG uptake values, which means “typical”WAT may produce the beige fat cells or brown fat cells.(3) Effect of cold acclimation on adipose tissue morphology in tree shrew: with prolongation of the time of cold acclimation, in hematoxylin- eosin stained sections can be found, axillary brown adipocytes in fat droplets were smaller and located in perivascular brown adipocyte lipid droplets were relatively smaller in cold acclimation group compared with that of control group. There were significant changes in the fat droplets in the subcutaneous “typical” WAT in the abdomen. Cold acclimation of 0d is typical of a single bubble of fat cells, the center of the cell has alarge lipid droplets. After cold acclimation for 4 weeks, the cells were divided into small lipid droplets in a single bubble. During the cold acclimation for 7 weeks, more small fat droplets were found in the cells. This indicates that cold acclimation not only changes the morphology of brown fat cells, but also changes the morphology of white fat cells.It showed that control group of tree shrews armpit bat UCP1 expression of Tan areas less, with the extension of cold acclimation time, parts of the same tissue UCP1 positive Tan area increases and deepen the color that after cold acclimation UCP1 expression may increase by immunohistochemical staining. In cold acclimation tree shrews increase heat production by increasing typical BAT UCP1 expression, and through the capillary transit for the body to provide heat, in response to cold stress.With prolonging of time cold acclimation, cold acclimation group tree shrew in abdominal omental white fat cells appear differentiation, not only lipid droplets become smaller, but there is a UCP1 positive region, show certain characteristics of brown fat cells, probably is beige fat cells. That first discovered the cold acclimation in beige adipocytes induced by morphological evidence of tree shrew WAT in abdominal omental.Immunity fluorescence can be found that control group of tree shrews “typical”BAT UCP1 positive red fluorescent small and dim, and the cold acclimation group of tree shrews armpit BAT UCP1 positive fluorescent brighter, and can see some positive fluorescence of elliptic points, is likely to be the mitochondria. Cold acclimation group in abdominal omental WAT found some UCP1 positive red fluorescence of the elliptic points, may be in the mitochondria of UCP1 content.These cells are may be cold acclimation induced Beige fat cells. For the first time we found and should permit the immunohistochemistry in cold induced morphological evidence of tree shrew in abdominal omental WAT Beige fat cells.(4) The tree shrews’ fat cells by flow cytometric analysis under cold acclimation:the first successful exploration of the use of tree shrew adipose tissue sample making method of flow, the first use of flow cytometry to cold acclimation under the tree shrew fat cells were compared and analyzed.Cold acclimation 28 d the tree shrews abdominal omental, groin "typical" WATsingle R1 group is 5.70% of the cells showed positive UCP1. New cell population R2 group appeared in "typical" WAT in the time of 49 d. R1 group of 69.64% of the cells showed positive for UCP1. R2 had 95.28% of the cells showed positive for UCP1.Cold acclimation makes UCP1 expression positive cell population in WAT.To sum up, cold acclimation not only makes the tree shrews “typical” BAT tissue hyperplasia, the production of thermal activity increased, also induced a the “typical”WAT Beige fat cells appeared. So tree shrews in cold acclimation enhanced BAT thermogenic activity, beige fat cells, to increase heat production, and make up the "typical" BAT non shivering thermogenesis, to deal with the cold environment. At the same time as the beige and brown fat cells consume a lot of energy in UCP1 heat production, plays an important role in the regulation of body mass. How safe effective induced in WAT with functional activity of beige fat cells, has already become a hot problem in the treatment of human obesity and metabolic syndrome. |
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