A BASIC APPROACH TO ASSOCIATION OF INSULIN RESISTANCE WITH TNF α IN COWS WITH FATTY LIVER

Research Project

Project/Area Number	12660277
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Basic veterinary science/Basic zootechnical science
Research Institution	RAKUNO GAKUEN UNIVERSITY
Principal Investigator	OIKAWA Shin RAKUNO GAKUEN UNI. VETERINARY MEDICINE ASSOCIATEPROFESSOR, 獣医学部, 助教授 (40295895)
Co-Investigator(Kenkyū-buntansha)	TAKEHANA Kazushige RAKUNOGAKUEN UNI. VETERINARY MEDICINE PROFESSOR, 獣医学部, 教授 (80137413) HAGIWARA Katsuro RAKUNO GAKUEN UNI. VETERINARY MEDICINE ASSOCIATEPROFESSOR, 獣医学部, 講師 (50295896)
Project Period (FY)	2000 – 2001
Project Status	Completed (Fiscal Year 2001)
Budget Amount *help	¥3,000,000 (Direct Cost: ¥3,000,000) Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000) Fiscal Year 2000: ¥1,600,000 (Direct Cost: ¥1,600,000)
Keywords	COW / FATTY LIVER / INSULIN RESISTANCE / TNF α / FASTING / ETHIONINE
Research Abstract	It has been recently reported that cows with insulin resistance are sometime observed during the periparturient period, and their milk production are remarkably decreased. It is pointed out that fatty liver is closely linked to that pathogenesis. Tumor necrosis factor ct (TNFα) secreted from fatty cell is considered to be the most important factor in the insulin resistance. We designed two experiments for induction of fatty liver. In experiment-1, cows were fasted for 4 day to be fallen into negative energy balance. Moreover, as experiment-2, cows were administrated ethionine, analogous substance of methionine, to reduce the production of proteins in the liver. Insulin resistance and TNF α of used cows were analyzed in each experiment. Experiment-1 1. Liver triglyceride (TG) content was apparently increased after fasting. 2. The increase of insulin resistance was observed in the development of fatty liver. 3. Serum concentration of TNFα was not significantly changed in the fasted cow. 4. In micromorphological analysis of liver, hepatic basal lamina in the cow with fatty liver remarkably became thicker compared to that in control. Experiment-2 1. Liver TG contents were remarkably increased in ethionine-treated cows. 2. Serum concentration of apolipoprotein B-100 was significantly decreased in the development of fatty liver. 3. Hepatic lipidosis apparently induced insulin resistance. 4. Hyperglycemia and hyperinsulinism were observed in treated cows. 5. The apparent association of fatty liver with serum concentration of TNFα was not detected. From these results, two experiments were suggested to be effective for induction of fatty liver. Although TNFα of sampled liver tissues were analyzed biochemically and histologically, its relevance to hepatic lipidosis was not detected. We are planning to improve TNFα determination and histological specimens to scrutinize these experiments.