Evaluation of Nesfatin-1 Expression in Lean, Overweight, and Diabetic Cats
Chapter Two Background: Rates of obesity and diabetes mellitus are increasing in domestic cats. Nesfatin-1 is a protein hormone implicated in controlling food intake and maintaining glycemic control. The role of nesfatin-1 in the pathophysiology of obesity and diabetes mellitus in cats has not been evaluated. This study aimed to characterize NUCB2/nesfatin-1 mRNA expression in feline gastric, pancreatic, abdominal adipose, and skeletal muscle tissue, and to evaluate how tissue nesfatin-1 expression differs between lean, overweight, and diabetic cats. Methods: Case control study. Four lean, three obese, and five diabetic cats were sampled. RNA was extracted from pancreas, stomach, abdominal fat, and skeletal muscle, and a one-step RT-PCR was performed. Relative NUCB2/nesfatin-1 expression was assessed by the comparative 2-Ct method. Results: NUCB2/nesfatin-1 mRNA expression was highest in the pancreas and there was a wide variance in tissue expression in all cats. Expression tended to be marginally decreased in pancreatic tissue of overweight cats in comparison to lean cats. NUCB2/nesfatin-1 expression in the gastric and pancreatic tissue of diabetic cats showed a biphasic pattern. Two diabetic cats had similar expression patterns to lean cats, while three diabetic cats had decreased expression compared to lean cats. This biphasic expression was unrelated to the body condition or treatment status of these diabetic cats. No patterns of expression were identified in adipose and muscle tissue. Conclusions: The pancreas had the highest levels of NUCB2/nesfatin-1 mRNA expression in cats. Changes in expression in diabetic cats were most pronounced in the stomach and pancreas. The biphasic pattern of expression in diabetic cats may reflect differences in pancreatic islet health and function in these cats. The clinicopathological implications of these changes need to be investigated further. Future studies may involve assessing changes in nesfatin-1 mRNA expression in conjunction with changes in nesfatin-1 tissue protein expression and circulating nesfatin-1 concentrations. Chapter Three Background: Obesity and diabetes mellitus are increasing issues in humans and domestic cats. Diabetes mellitus in cats shares similar clinicopathologic features to type 2 diabetes mellitus in humans. Nesfatin-1 is a recently discovered protein hormone that has been implicated in the development of obesity and diabetes, and alterations in plasma nesfatin-1 concentrations have been documented in type 2 diabetic humans. This study aimed to evaluate whether plasma nesfatin-1 concentrations in cats were associated with adiposity or insulin resistance, and to determine if nesfatin-1 concentrations were altered by diabetic treatment. Influences of sex and age on nesfatin-1 concentrations were also assessed. Methods: Case control study. Plasma was collected from 13 lean and 13 obese non-diabetic cats, and eight newly diagnosed and five long term diabetic cats. Newly diagnosed diabetic cats were sampled before and after four weeks of diabetic treatment. Plasma nesfatin-1 levels were measured by a rat nesfatin-1 ELISA, which was validated for use with feline plasma. Results: Median plasma nesfatin-1 concentrations in newly diagnosed and long-term treated diabetic cats showed a slight upward trend in comparison to lean and overweight non-diabetic cats, though the highest nesfatin-1 concentrations were seen in a subset of lean healthy cats. However, overall differences in plasma nesfatin-1 concentrations in lean, overweight, and diabetic cats were not statistically significant. Sex and age were also not significantly associated with plasma nesfatin-1 levels. Newly diagnosed diabetic cats showed a statistically significant decrease in nesfatin-1 concentrations following short-term treatment, which may suggest a link between decreased nesfatin-1 concentrations and diabetic treatment in cats. Conclusions: Our results suggest that changes in plasma nesfatin-1 concentrations may be more related to diabetic status and the presence of insulin resistance as opposed to differences in adiposity or body condition, though further research is required to determine the significance of this relationship. There may be additional, currently unknown factors that increase nesfatin-1 concentrations in cats. Future studies may include longitudinal studies to investigate if nesfatin-1 concentrations change as cats develop increasing adiposity, insulin resistance, and eventually become clinically diabetic.
NUCB2, Nesfatin-1, Diabetes Mellitus, Cat
Master of Science (M.Sc.)