Zinc Alpha2 Glycoprotein Reduce Nutritional Obese Mice Fat Deposition Mechanism Research

Objectives: To observe the expression of Zinc-alpha2-glycoprotein and mitochondrialbiogenesis related factors in the adipose tissues of db/db mice, and to explore theeffects of rosiglitazone.Methods: Male db/db mice and their nondiabetic controls (db/+m) were obtained fromNation Recource Center for Mutant Mice Model Animal Research Center (MARC). Theywere housed individually in plastic cages with bedding and allowed free access to normallaboratory chow and tap water. The animal rooms were controlled for temperature,humidity and light. All mice were used for experiments at8weeks of age after1week ofacclimation period. The animals were divided into experimental groups matched for bothbody weights and blood glucose levels. The db/db mice (n=28) and control db/m mice(n=14) received normal mouse chow. For the db/db model, mice received rosiglitazone(10mg/kg/day) by oral gavage daily for either4or8week. The body weight, plasmaglucose level, plasma lipid profile, FFA and ZAG were assessed after treatment. Reversetranscriptase polymerase chain reaction (RT-PCR) and Western-blotting were used todetect the mRNA and protein expression of ZAG and mitochondria biogenesis relatedgenes, such as peroxisome proliferation receptor gamma assisted activating factor1alpha (PGC-1α), nuclear respiratory factor1/2(NRF-1/2) and mitochondrial transcriptionfactor A (mtTFA). The visceral adipose tissue section were stained with H&E.Results: The amount of food and water, weight gain, visceral fat mass, body fat ratio,fasting blood glucose, cholesterol, triglyceride, free fatty acids were significantly higherin spontaneous diabetes mellitus (db/db) mice than non diabetic (db/m) mice. In db/dbmice, the expression levels of ZAG and mitochondrial biogenesis related factors(PGC-1α, NRF-1/2, mtTFA) were significantly lower than the non diabetic mice. Aftertreatment with rosiglitazone, the size of adipocytes were significant smaller andexpression of ZAG and mitochondrial biogenesis related factors were significantimproved compared with control db/db mice. Conclusions: Rosiglitazone reduces fat accumulation, particularly in the visceralcompartment, improves lipid metabolism by up-regulation the expression of ZAG andmitochondrial biogenesis related factors such as PGC-1α, NRF-1/2and mtTFA. Objectives: To establish high-fat diet induced nutritional animal model and explore theeffects of ZAG on expression of mitochondrial biogenesis related factors in the adiposetissue.Methods: Male C57BJ/6mice were fed either with a normal food, or with a high-fatfood starting when the mice were four weeks old and for a total of10additional weeks.After the nutritional models were established, mice were administered withpcDNA3.1(-)-mZAG plasmid by tail venus injection for a total of two weeks.To assessZAG induced anti-obesity, we observed the weight, epididymal fat and mitochondrialbiogenesis.Results: High-fat diet could induce abdominal obesity in mice model. The amount ofweight gain, visceral fat mass, body fat ratio, fasting blood glucose, cholesterol,triglyceride, free fatty acids and LDL were significantly higher in high-fat food groupthan normal food group, while the expression of ZAG and mitochondrial biogenesisrelated factors (PGC-1α, NRF-1/2, mtTFA) were significantly lower than the normalfood group. On the other hand, ZAG could decrease the weight increasing, body fatratio, visceral fat and the levels of serum TC, LDL and FFA. The size of adipocyteswere significant smaller, the expression of mitochondrial biogenesis related factors(PGC-1α, NRF-1/2, mtTFA) and ZAG in visceral adipose tissues were significantlyincreased after overexpression of ZAG.Conclusions: ZAG could alleviate body weight of the nutritional obesity mice byreducing visceral fat accumulation which associated with ZAG promoting expression ofmitochondrial biogenesis related factors (PGC-1α, NRF-1, mtTFA).