2. โข Cow metabolism during transition
โข Fatty liver and related disorders
โข Transcriptional control of lipid/energy
metabolism: PPARs
โข PPAR-alpha agonists in veterinary
3. The last 3 wk before to 3 wk after parturition
๏ฎ Tremendous metabolic adaptations to support lactation
๏ฎ Most diseases occur during or soon after this time
4. Prepartum Postpartum Increase
Hepatic Blood Flow 1140 l/h 2099 l/h + 84%
DMI 9.8 kg/d 14.1 kg/d + 44 %
Liver Oxygen Utilization 1619 mmol/h 3159 mmol/h + 95 %
Daily Metabolic Activity
per gram of liver
4.4 mmol O2/g 8.6 mmol O2/g X 2
Glucose Release from
Liver
1356 g/d 2760 g/d X 2
Big changes over a very short time highlight the tremendous
metabolic adaptations necessary to adequately support lactation
5. -10
0
10
20
30
40
0 35 70 105 140 175 210 245 280
Energy Ingested
Energy Required
NegativePositive
Energy Balance = Energy Ingested - Energy Required
DIM
Mcal/day
Adapted from Bauman and Currie 1980
After parturition extra energy
requirement for milk production
is not met by feed energy intake
Lipolisis
Parturition
8. Fatty liver is a common condition, up to 50 % of dairy cows
9. Fatty liver has detrimental effects on
health, productivity and fertility
The Liver sits at the crossroads of
metabolism
Its integrity is vital to all physiological
processes
10. Disorder Association Reference
Displaced abomasum +++ Wada et al., 1995; Rehage et al., 1996
Impaired immunoreactivity ++ Wentink et al., 1997; Zerbe et al.,
2000
Ketosis +++ Grรถhn et al., 1987; Veenhuizen et al.,
1991
Laminitis + Fronk et al., 1980; Rehage et al., 1996
Mastitis ++ Morrow et al., 1979
Metritis ++ Haraszti et al., 1982; Heinonen et al.,
1987
Milk fever + Higgins and Anderson, 1983; Grรถhn et
al., 1987
Retained placenta + Haraszti et al., 1982; Heinonen et al.,
1987
Bobe 2004
12. Parameter Association Reference
First ovarian activity ++ Reid et al., 1983; Rukkwamsuk et al., 1999c
First ovulation + Reid et al., 1983
First estrus + Paulovรก et al., 1990; Jorritsma et al., 2000
First insemination + Reid et al., 1983
Days open ++ Heinonen et al., 1987; Paulovรก et al., 1990
Pregnancy rate ++ Haraszti et al., 1982; Jorritsma et al., 2000
Services/cow + Schรคfer et al., 1988; Paulovรก et al., 1990
Bobe 2004
13.
14. โข All the cells regulate their metabolism in
response to changes in the environment and
metabolize fuels according to their availability
MODERN VIEW
Nutrients can directly
regulate metabolism in a
hormonal independent
manner
CLASSICAL VIEW
metabolic adaptations
are controlled only by
hormonal or neuronal
signals
16. NUCLEAR RECEPTOR LIGAND
Thyroid hormone R Thyroid hormone
Glucocorticoid R Cortisol
Estrogen R Estrogen
Progesterone R Progesterone
Androgen R Testosterone
PPAR Lipids
Receptors found
within the nucleus
Bind directly to DNA
and regulate gene
expression
Ligand activated
transcription factors
17. โข Nuclear receptors
involved in the
transcriptional regulation
of lipid metabolism and
energy balance
โข Fatty acids and their
derivatives (Acyl-CoA &
eicosanoids) are the
natural ligands of PPAR
ANIMATION
22. โข fenofibrate, gemfibrozil
โข used to lower triglycerides and raise
HDL-C in dyslipidemia to reduce risk of
cardiovascular events
โข 2-phenoxy-2-methyl-propionic acid
โข Hepagen
โข used to treat fatty liver, related metabolic
disorders and improve energy balance
25. 40 Holstein cows (2ยฐ-5ยฐ lactation)
โข Treated group: 50 ml of Hepagenยฎ I.M. at calving, 3d postpartum and 5d postpartum
โข Control group: 50 ml of physiological solution (NaCl 0.9%)/ head at calving, 3d
postpartum and 5d postpartum
50ml/cow
50ml/cow
50ml/cow
Biopsy
Biopsy
Biopsy
26. Liver sections stained with toluidine blue
Sciorsci 2009
30 ฮผm
CONTROLTREATED
1 d 15 d 30 d
8.6%
9.0%
0.3% 0.1%
0%
1%
2%
3%
4%
5%
6%
7%
8%
9%
10%
15 d 30 d
Liver Fat
Control
Treated
P < 0.001
27. Liver sections stained with haematoxylin-PAS to highlight the presence of glycogen (purple). Sciorsci 2009
30 ฮผm
CONTROLTREATED
1 d 15 d 30 d
28. 26
27
28
29
30
31
32
33
34
35
36
1 3 5 10 15 30 40
g/L
Days from parturition
Control
Hepagen
โข Albumin concentration significantly higher in the treated group
โข Albumin concentration in the control group slightly lower than the normal range
29. 3.70 4.24
5,46
6.47
-
2
4
6
8
11 d 13 d
ng/ml
Progesterone
74
50
-
20
40
60
80
days
Days to 1ยฐ Heat
121
92
-
50
100
150
days
Days open
50
6457
71
-
20
40
60
80
days
Pregnancy rate
Sciorsci 2009p<0.05
HEPAGENCONTROL
31. 0.4
0.6
0.8
1.0
1.2
-10 10 30 40
BHBmmol/L
44%
39%
28%
17%
6% 6%
0%
25%
50%
10 30 40
CONTROL
HEPAGEN
Bouda et al. 2008
p<0.05
Open days: lower in Control than in Treated group
109.9 vs. 118.5 days
37. Monitor and record for diseases occurring during the early
lactation period in the herd:
โข Lactational incidence risk (LIR): #affected / # of calvings (at
risk) in the same time period
โข Case de๏ฌnitions/Con๏ฌdence of diagnosis grade
โข Define targets for acceptable levels of incidence
Reduce risk of
postpartum diseases
To complement transition cow management programs and
herd preventive health care programs
41. Daily Monitoring of Each Cow for First 10
Days after Calving
(Temperature and Physical Exam)
Early Identification and Treatment of
Problem Cows
Best with Fresh Cow
Medicine Programs
42. โข Difficult
โข No specific symptoms
โข Diagnosed by biopsy
โinvasive technique
โhemorrhage, infection, death
โข New promising ultrasound technology
43. โข Cows having problems from the beginning of
lactation
โข Rapid weight and BCS loss, reduced feed intake
โข Presence of ther diseases
โข Diseases more severe and less responsive
โ Milk fever cows that relapse and become downers
โ Ketotic cows that donโt respond to treatment
โ Chronic mastitis cows
โ Repeat breeders that defy all treatments
โ Cows that relapse or go from one disease to another
โ Reduced milk production
โ Cows that are frequently culled
