Source: IOWA STATE UNIVERSITY submitted to
PREVENTION OF FATTY LIVER IN DAIRY COWS BY GLUCAGON AND GLYCEROL
 
PROJECT DIRECTOR: Beitz, D. C.
 
PERFORMING ORGANIZATION
ANIMAL SCIENCE
IOWA STATE UNIVERSITY
AMES,IA 50011
 
NON TECHNICAL SUMMARY: Dairy cows are susceptible to metabolic and infectious diseases in early lactation. One significant metabolic disease is fatty liver, a major accumulation of fat in the liver, which usually occurs in the first 1-3 weeks after calving. Some estimates suggest that up to 50% of U.S. dairy cows have mild to pathological fatty liver in early lactation, costing millions of dollars in treatment and production losses. Fatty liver seems to cause increased incidences of other disorders such as ketosis, metritis, and mastitis and decreased reproductive efficiency. Currently, pathological fatty liver can neither be prevented consistently nor treated effectively by nutrition or any other means. We have published evidence that glucagon, an important mammalian hormone, can be used to greatly speed up removal of fat from livers of affected dairy cows. We propose to test whether glucagon, when given on the day of calving, will prevent the development of fatty liver. Our goal is to develop the technology of using glucagon to prevent fatty liver and to thereby improve the health and well-being of U.S. dairy cows. Prevention and treatment of fatty liver will avoid millions of dollars in financial losses for dairy farmers. The results will lead to management options that enhance the health and life expectancy of dairy cows and improve the sustainability and profitability of dairying.
 
OBJECTIVES: 1. Determine whether subcutaneous injections of glucagon and/or oral administration of glycerol on the day of parturition prevents fatty liver. 2. Identify (rule in/rule out) and quantify metabolic processes in the etiology of fatty liver by which subcutaneous glucagon injections and/or oral administration of glycerol prevents fatty liver.
 
APPROACH: Cows will be fed during the dry period supplemental corn to generate postpartal fatty liver. On the day of parturition, saline or glucagon (injected) and either with or without supplemental glycerol (oral) will be administered to each cow for 16 consecutive days. Liver and adipose tissue biopsies and blood samples collected before, during, and after the treatment period will be collected to determine effectiveness of treatments to prevent fatty liver and to study why the effect occurs. Liver will be assayed for lipid and glycogen content and rates of gluconeogenesis, adipose tissue will be assayed for lipid mobilization, and blood will be assayed for several metabolites, hormones, and apolipoproteins to complete objectives. Our goal is to develop a technology for using glucagon in commercial dairy herds for prevention of fatty liver.
 
CRIS NUMBER: 0192651 SUBFILE: CRIS
PROJECT NUMBER: IOW06605 SPONSOR AGENCY: NIFA
PROJECT TYPE: NRI COMPETITIVE GRANT PROJECT STATUS: TERMINATED MULTI-STATE PROJECT NUMBER: (N/A)
START DATE: Sep 1, 2002 TERMINATION DATE: Aug 31, 2005

GRANT PROGRAM: SUSTAINING ANIMAL HEALTH & WELL BEING
GRANT PROGRAM AREA: Animal Systems

CLASSIFICATION
Knowledge Area (KA)Subject (S)Science (F)Objective (G)Percent
305341010102.2100%

CLASSIFICATION HEADINGS
KA305 - Animal Physiological Processes
S3410 - Dairy cattle, live animal
F1010 - Nutrition and metabolism
G2.2 - Increase Efficiency of Production and Marketing Systems


RESEARCH EFFORT CATEGORIES
BASIC 50%
APPLIED 50%
DEVELOPMENTAL (N/A)%

KEYWORDS: dairy cows; fatty liver; glucagon; glycerol; disease prevention; dairy cattle; animal physiology; animal metabolism; parturition; livestock management; performance evaluation; quantitative analysis; etiology; adipose tissue; biopsy; blood samples; gluconeogenesis; rate determination; tissue analysis; metabolites; animal hormones; apo lipoproteins

PROGRESS: Jan 1, 2004 TO Dec 31, 2004
Twenty-four multiparous Holstein cows were assigned randomly to Saline (control), 7.5 mg/d, or 15 mg/d of glucagon treatment groups with 8 cows per group. During the final 4 weeks of gestation, all cows were supplemented with 6 kg of cracked corn in addition to their regular NRC-based diet to stimulate the development of fatty liver disease postpartum. Beginning at day 2 postpartum, cows were injected subcutaneously with saline or 7.5 mg/d or 15 mg/d of glucagon for 14 days. Liver samples were obtained by puncture biopsy at -4, 2, 6, 9, 16, 20, 27, 34, and 41 days postpartum and analyzed for lipid composition and glycogen. Blood samples were collected from the coccygeal vein at days 1 through 17, 20, 27, 34, and 41 postpartum and analyzed for blood metabolites. Feed intake was monitored twice daily from day 1 through day 17 postpartum. Milk samples were collected at the days of liver biopsies and analyzed for different milk components. Milk production was recorded throughout the entire sampling period. Data were analyzed as repeated measures using the mixed models procedure of SAS. Glucagon administration at 15 mg/d dosage prevented liver tiracylglycerol accumulation during treatment period (P<0.02). Plasma glucose concentration was increased in 7.5 mg/d and 15 mg/d of glucagon treatment groups (P<0.0001) in a dosage-dependent manner (P<0.02). Plasma nonesterified fatty acid (NEFA) concentration was decreased during treatment period in 7.5 mg/d and 15 mg/d of glucagon treatment groups (P<0.05 and P<0.007 respectively). Glucagon injections did not significantly change plasma beta-hydroxybutyrate and urea concentrations. Plasma insulin concentration was increased in 7.5 mg/d and 15 mg/d of glucagon treatment groups (P<0.01 and P<0.001 respectively). Glucagon administration did not cause any significant changes in feed intake and milk production. Milk lactose, fat, and protein concentrations were not altered significantly by glucagon injections. However, there was a decrease in milk urea concentration in 7.5 mg/d and 15 mg/d of glucagon treatment groups (P<0.02 and P<0.002 respectively). In conclusion, glucagon can be used to prevent fatty liver development in transition dairy cows because of its NEFA lowering effect and potency to increase blood glucose and insulin concentrations without altering cows' feed intake and milk production.

IMPACT: 2004-01-01 TO 2004-12-31 We expect this research could lead to a glucagon product that could be commercially available for dairy farmers to decrease severity of fatty liver of transition dairy cows.

PUBLICATION INFORMATION: 2004-01-01 TO 2004-12-31
Nafikov, R.A., B.N. Ametaj, G. Bobe, K.J. Koehler, J.W. Young, and D.C. Beitz. 2004. Prevention of fatty liver in transition dairy cows by subcutaneous glucagon injections. A-41, 12th Int. Conf. Prod. Dis. Farm Animals. p. 40.

PROJECT CONTACT INFORMATION
NAME: Good, C.
PHONE: 515-294-4544
FAX: (N/A)