Lipodysregulation and Type 2 diabetes in TALLYHO/Jng Mice

The prevalence of reported diabetes was 2.9 times higher in overweight than in non-overweight persons as proved by the National Health and Nutrition Examination Survey (NHANES III) data. The majority of individuals with type 2 diabetes develop insulin resistance associated with overall obesity. Several lines of evidence indicate that many of the metabolic derangements associated with obesity and type 2 diabetes originate from dysregulation of lipid metabolism.

TALLYHO/Jng (TH) mice are a newly established inbred polygenic model for obesity and type 2 diabetes. These mice are characterized by insulin resistance, hyperinsulinemia, diabetes (males) obesity, and dyslipidemia including hypertriglyceridemia (HTG). TH male mice rapidly develop HTG at a very young age before the onset of overt diabetes, and this HTG is accompanied by hyperinsulinemia, and preceded glucose intolerance.

The goal of this study is to characterize the lipodysregulation in TH mouse. In order to achieve this goal, we measured tissue triglyceride content in non-adipose tissue, and hepatic fatty acid β-oxidation rates in diabetic TH mice. TH male mice exhibit significantly elevated TG content and lipid accumulation in skeletal muscle, liver, and kidney. Attenuated hepatic fatty acid oxidation was also featured in male diabetic TH mice although it was not statistically significant. It is likely speculated that impaired fatty acid oxidation in liver may be in part responsible for the HTG, elevating TG content in peripheral tissue including the skeletal muscle, which may be attributable to the impaired insulin sensitivity and diabetes in male TH mice. Elucidating the mechanism of lipodysregulation in diabetic model of TH mice will provide insights into the causes and mechanisms underlying the metabolic complications of insulin resistance and diabetes and ultimately improved therapeutic strategies for prevention and treatment of type 2 diabetes.