This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The Zucker diabetic fatty (ZDF) rat is a well studied model of obesity and Type 2 Diabetes Mellitus. These animals become insulin resistant early on and frankly diabetic by 12 weeks after birth. Adipocyte resistance to the antilipolytic activity of insulin, results in an elevated concentration of circulating free fatty acids in ZDF rats while hepatic insulin resistance leads to inappropriate rates of glucose production. Nonetheless, hepatocytes from these rats maintain elevated rates of de novo lipogenesis and a 3-fold decrease in fat oxidation and this has been implicated as a mechanism for the development of hepatic steatosis in the ZDF rat. However, it is not known 1) how these in vitro results translate to in vivo hepatic metabolism in the ZDF rat;2) how abnormal hepatic fat oxidation progresses during the advancement of the phenotype or;3) how obvious disruptions of hepatic energy metabolism integrate with the known disruption of hepatic glucose metabolism.
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