Creation of a mouse model with consitutively activated RHEB (RAS Homologue enriched in brain) in adipose tissue
Kim, Jessica Min Joung
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According to the CDC, approximately one third of the adults in the United States are obese consequentially causing a rise in obesity related metabolic diseases such as diabetes type 2. Major catabolic and anabolic pathways become disregulated in obesity, causing problems in energy homeostasis. One major nutrient sensor that plays an essential role in energy homeostasis is mammalian target of rapamycin complex 1 (mTORC1). mTORC1 is necessary for the proper growth and development of adipocytes. It also regulates vital adipose tissue pathways like lipolysis and lipogenesis. Therefore our lab has focused much research into better understanding mTORC1 role in energy homeostasis and how it is affected in diseases states. Previous research in our lab, using 3T3-L1 adipocytes, discovered that mTORC1 decreases mRNA levels of the lipolytic enzymes adipose triglyceride lipase (ATGL) and hormone sensitive lipase (HSL). In order to get a better picture of mTORC1's role in lipid metabolism, we decided to create a mouse model with conditional expression of constitutively active Rheb (caRheb) in adipose tissue. As Rheb is the major activator of mTORC1, this system will allow us to transiently activate mTORC1 specifically in adipose tissue. For that, we created mice with whole body expression of caRheb under the tetracycline response element-containing promoter. We bred these animals with transgenic mice expressing reverse tetracycline-controlled transactivator (rtTA) under the adiponectin promoter. We have successfully obtained double transgenic mice that will be used to study the mTORC1 pathway in vivo.
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