FAT LIVER

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Fræðaþing landbúnaðarins 2005 
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Energy metabolism in the periparturient dairy cow 
Grétar Hrafn Harðarson1 and Klaus Lønne Ingvartsen2 
1 Agricultural University of Iceland, 2 Danish Institute of Agricultural Science 
 
Introduction 
Production diseases i.e. diseases associated with improper nutrition or management are 
common and very costly in Iceland. The diseases listed in this include: the fat liver 
syndrome, ketosis, laminitis, mastitis, milk fever, retained placenta, metritis and 
infertility. The diseases occur mainly around calving. They are all interrelated and form 
the so-called periparturient disease complex. 
The production year of cow can be split up into three phases according to metabolic state 
of the animal (Holtenius 1994). Two to three weeks before calving a phase of catabolism 
starts where emphasis is put on the preparation for parturition and the initiation of 
lactation. This phase will last 8-12 weeks into the lactation depending on the feeding and 
management strategies and the genetic potential of the animal. A period of equilibrium 
follows the phase of catabolism where the partition of nutrients neither favours lactation 
nor increased weight gain. The last period of the production year is a phase of anabolism 
where the emphasis is put on increased weight gain as a long-term preparation for the 
next lactation. 
Table 1. A list of some important biological processes or metabolic changes associated with transition to 
lactation in ruminants. 
Process or metabolism Response Tissue involved 
Fat metabolism Ð de novo fat synthesis 
Ð absorption of fatty acids 
Ð esterification of fatty acids 
Ï lipolysis 
Ï use of lipid as energy 
 
Adipose tissue 
 
 
 
Other body tissues 
Glucose metabolism Ï size of the liver 
Ï blood flow 
Ï rate of gluconeogenesis 
Ð use of glucose as energy 
Liver 
 
 
Other body tissues 
Protein metabolism Ð protein synthesis 
Ï proteolysis 
Ï protein synthesis 
 
Muscular tissue 
 
Other body tissues 
Feed intake Ï feed intake 
 
Central nervous system
Digestion Ï hypertrophy of the digestive tract 
Ï absorption rate and capacity 
Ï metabolic activity 
Digestive tract 
 
The phase of catabolism is the only period causing strain on the cow. In this period for 
example the energy requirements increase by more than 300% in high yielding cows. 
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These tremendous changes call for a coordination of the biological processes in different 
tissues resulting in metabolic changes (see table 1) that try to ensure that the cow’s 
genetic potential for milk yield is exploited but at the same time maintaining 
physiological homeostasis. When the regulatory mechanism fails one gets physiological 
imbalance leading to high risk of disease. 
Metabolic regulation and clinical biochemistry 
The endocrine system plays an important role in the metabolic regulation. The hormonal 
regulation comprises both homeorhesis and homeostasis. Bauman and Currie (1980) 
defined homeorhesis as ”the orchestrated or coordinated changes in the metabolism 
necessary to support a physiological state”, with an adaptation to a new equilibrium 
taking place over days or weeks. Homeorhesis is e.g. responsible for the different phases 
in the production life of the cow. Homeostasis on the other hand can be defined as the 
regulation that maintains the equilibrium of the animal in different nutritional and 
environmental conditions; a regulation that takes place from minute to minute. 
The ratio of growth hormone to insulin is high in blood of cows in early lactation, which 
induces mobilisation of fatty acids from adipose tissue triglycerides (TG). The sensitivity 
of the adipose tissue to lipolytic signals (epinephrine and norepinephrine) is also greatly 
enhanced in early lactation (Theilgaard et al., 2002; Underwood et al., 2003). Fatty acids 
released from adipose tissue circulate as nonesterified fatty acids (NEFA), which are a 
major source of energy to the cow during this period. The percentage of blood NEFA 
utilized by the liver is fairly constant, hence the concentration of NEFA in blood reflects 
the degree of adipose tissue mobilisation (Pullen et al., 1989). In liver NEFA may be 
transformed into triglycerides, be incorporated into lipoproteins and released into the 
circulation, be oxidized for energy or be converted to ketone bodies. 
Consequently, stressors and poor nutritional management causing reduction in voluntary 
dry matter intake (DMI) will result in large increases in NEFA around calving (Drackley, 
1999; Ingvartsen and Andersen, 2000). The levels then decrease gradually in the first six 
weeks of lactation with cows developing ketosis decreasing more slowly (Schwalm and 
Schultz 1976). 
The use of glucose is reduced in most tissues in early lactation and instead the use of fatty 
acids and ketone bodies is increased. Despite the reduced use of glucose and a 
considerable increase in the gluconeogenesis in liver and kidney, the glucose 
concentration normally drops in early lactation. 
The principle precursors of ketone bodies are butyrate from the rumen and NEFA derived 
from fat mobilisation. The major tissues involved are the liver and the rumenoreticulum 
epithelium. Butyrate is metabolised into beta-hydroxy-butyrate (BHB) on absorption 
from the rumen. This BHB production forms the basal concentration of ketone bodies in 
ruminants. The ketogenesis in hepatic tissue generally increases the level of ketone 
bodies in blood. The concentration of ketone bodies in blood is determined by production 
rate rather than utilization as they go hand in hand until a point is reached when 
utilisation is maximised (Bergman 1971). 
Several workers have found that in normal cows the ketone bodies in blood rise gradually 
from calving, reaching a peak 20-30 days postpartum and drop after that. This being a 
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very similar pattern as shown by the incidence of clinical ketosis. The point at which 
physiological ketosis becomes pathological is not clearly defined. Possibly 
hypoglycaemia is necessary to produce clinical symptoms (Kronfeld 1972). 
For all the above-mentioned metabolites, there is a very considerable individual variation 
between cows (Ingvartsen et al., 2003a; Ingvartsen et al., 2003b) illustrating that some 
cows have a higher risk of developing production diseases such as the fatty liver 
syndrome and ketosis. 
Fatty liver is the term used to describe livers that contain more visible lipid in liver cells 
than one expects to see in that organ. This includes the physiological accumulation seen 
in lactating cows, but clinically normal animals may have fatty livers.The synthesis and 
transport of lipoprotein within the liver cell are processes requiring a small energy input. 
Any disturbance of this metabolism has the potential to inhibit lipoprotein synthesis or 
secretion. Triglyceride synthesis from incoming fatty acid, being less dependent on 
energy expenditure may continue, resulting in the accumulation of excess triglyceride in 
the liver cells. The fat accumulates in small globules which may fuse to form a large 
globule, if the condition prevails for some time. Severe fatty liver may not necessarily 
produce severe hepatic dysfunction and the liver can return to normal structure and 
function once the metabolic defect has been corrected, especially if the duration of the 
lipid accumulation has not been long (Jubb et.al. 1993). Bovine ketosis is associated with 
fatty liver with fatty infiltration most severe in the periacinar area of the liver i.e. the 
areas furthest away from the arterial blood supply. 
Methods and Materials: 
Sixty cows at the research station Stóra Ármót, 28 primiparous and 32 multiparous in 12 
blocks, were assigned to one of four treatments in a 2 x 2 factorial design. In the early 
dry period cows were given high dry matter forage with a medium digestibilty ad libitum. 
In the transition period i.e. 3 weeks before expected calving, the cow received different 
amounts of concentrates and good quality forage ad libitum. After calving the cows 
received good quality forage ad libitum and the amount of concentrates was increases at 
different rates until the maximum of 11 kgs was reached (table 2.). 
 
Table 2. Feeding programme 
________________________________________________________________________ 
 
* Primiparous heifers received 83% of this amount. 
 
Blood samples were collected weekly (weeks -3 to 8 and 10 and 12) at 9 am after feeding 
of forage but before concentrates were given. After collection the samples were 
immediately chilled in icy water, centrifuged and the serum frozen at -20°C. Serum 
Treatment Early dry period Transition period* Early lactation* 
LL 1.5 kg concentrates 0.3 kg conc./d/d 
LH 1.5 kg concentrates 0.5 kg conc./d/d 
HL 3.5 kg concentrates 0.3 kg conc./d/d 
HH 
Ad libitum medium 
quality forage 
3.5 kg concentrates 0.5 kg conc./d/d 
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analysis was carried out at the Research Centre Foulum. Needle biopsies of the liver 
were collected three times (-3, 1, and 3 weeks after calving). Microscopic smears stained 
with DiffQuik differential haemotological stain were used for the estimation of the degree 
of fatty infiltration using the 1 – 5 scale (Steen et.al. 1992). The effects were analysed 
using the mixed procedure (SAS Institute 1996). 
Results 
Table 3. The effects of parity and treatment on concentration of NEFA, glucose and BOHB in blood. 
 
Parameter Effect Est. Least Sq. 
Means 
P value 
1 5,2978 
2 5,1548 
NEFA log n 
µeq/l 
Prepartum 
Parity 
≥3 4,7512 
0,1918 
1 5,0946 
2 5,5090 
NEFA log n 
µeq/l 
Postpartum 
Parity 
≥3 5,5000 
0,0885 
HH 5,4981 
HL 5,2881 
LH 5,2314 
NEFA log n 
µeq/l 
Postpartum 
Treatment 
LL 5,4540 
0,0346 
1 3,7918 
2 3,8048 
Glucose mM/l 
Prepartum 
Parity 
≥3 3,7597 
0,8841 
1 3,5949 
2 3,3043 
Glucose mM/l 
Postpartum 
Parity 
≥3 NE 
0,2251 
HH 3,2947 
HL 3,4853 
LH 3,4016 
Glucose mM/l 
Postpartum 
Treatment 
LL NE 
0,3020 
1 0,8166 
2 0,9269 
BHB mM/l 
Prepartum 
Parity 
≥3 1,0116 
0,2926 
 
1 1,4233 
2 1,7367 
BHB mM/l 
Postpartum 
Parity 
≥3 1,7032 
0,4169 
HH 2,0108 
HL 1,5484 
LH 1,4447 
BHB mM/l 
Postpartum 
Treatment 
LL 1,4803 
0,0030 
 
The blood parameters measured in relation to energy metabolism in this work were 
NEFA, glucose and betahydroxybutyrate. Treatment had a significant effect on the 
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concentration of NEFA and BHB in the postpartum period, with the LH group showing 
the most favourable values while HH was the opposite. Week from calving had a 
significant effect on all parameters. NEFA and hepatocyte fat infiltration score had 
highest values in week 1, while glucose had the lowest value in week 2 and BHB had the 
highest values in week 3 (see fig. 1 and tables 3 and 4). 
 
 
 
 
 
Fig. 1. Effect of treatment (— — { — — HH, ---{--- HL, — — ‘ — — LH, ---‘--- LL) and 
parity ( — — { — — 1 , — — ‘ — — 2, — — … — — ≥3) on the concentration of NEFA, glucose 
and BHB. 
Parity in the postpartum period had a significant effect on the fatty infiltration of liver 
(see fig. 2 and table 5), where primiparous heifers showed minimum infiltration 
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compared with older cows. Treatment had not a significant effect but the LH group 
showed the most favourable results like for the blood metabolites. 
 
Table 4. Hepatocyte fat infiltration score and concentration of NEFA, glucose and BHB in relation to 
weeks from calving. 
 
Week Hepatocyte fat 
score 1 – 5 
NEFA 
Log n µeq/l 
Glucose 
mmol/l 
BHB 
mmol/l 
-3 0,4143 5,0154 3,6944 0,8798 
-2 4,8949 3,7058 0,9307 
-1 4,9297 3,7696 0,9469 
0 5,4316 3,9721 0,9160 
1 1,3930 6,1201 3,3763 1,4655 
2 6,0076 3,1185 1,9583 
3 1,0937 5,7172 3,2980 2,0189 
4 5,4974 3,3068 1,9394 
5 5,4521 3,3848 1,8739 
6 5,3111 3,4548 1,4771 
7 5,0784 3,4999 1,4368 
8 4,9581 3,4910 1,5295 
10 4,8580 3,4918 1,3427 
12 4,6788 3,5490 1,1684 
Prepartum P value < 0,0001 <0,0001 0,1855 
Postpartum P value 0,0198 <0,0001 <0,0001 <0,0001 
 
 
 
 
 
Fig 2. Effect of treatment (— — { — — HH, ---{--- HL, — — ‘ — — LH, ---‘--- LL) and 
parity ( — — { — — 1 , — — ‘ — — 2, — — … — — ≥3) on fatty infiltration in liver cells. 
 
 
 
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Table 5. The effects of parity and treatment on hepatocyte fat infiltration score and concentration of NEFA, 
glucose and BHB in blood. 
 
Parameter Effect Est. Least Sq. 
Means 
P value 
1 0,1400 
2 0,3517 
Hepatocyte fat 
score - 
Prepartum 
Parity 
≥3 0,7513 
0,7106 
1 0,1995 
2 1,8932 
Hepatocyte fat 
score - 
Postpartum 
Parity 
≥3 1,6374 
0,0003 
HH 1,2586 
HL 1,1329 
LH 1,0445 
Hepatocyte fat 
score - 
Postpartum 
Treatment 
LL 1,5375 
0,2955 
 
 
Discussion 
The avoidance of excessive body reserve mobilisation is of paramount importance as far 
as prevention of production diseases is concerned. In the current study the LH feeding 
regime shows the most favourable metabolic conditions. This is contrary to a number of 
reports which show the beneficial effect of generous prepartum grain feeding on the 
NEFA levels in plasma (Kunz and Blum, 1985; Ingvartsen et al., 1995; Minor et al., 
1998; Holcomb et al., 2001). Others, however, show no effect (Dann et al., 1999; 
Vandehaar et al., 1999). Holtenius et al. (2003) recently reported that cows fed a higher 
energy level during the dry period had a greater degree of insulin resistance before and 
after calving, which induced higher plasma NEFA concentrations compared to those in 
cows fed below requirements. This might explain the different results in studies 
examining the effect of dry cow feeding. The dip in dry matter intake in periparturient 
cows has been found to be negatively correlated with plasma NEFA (Ingvartsen et al., 
1995) and consequently much interest has been directed towards avoiding low dry matter 
intake. 
It is well known that a low energy diet in the dry period can cause a degeneration of the 
rumen epithelium and thereby a reduced volatile fatty acid (VFA) absorption capacity 
(Liebich et al., 1982; Mayer et al., 1986). Hence the theory of exposing the rumen toa 
acid load in order to stimulate the development of the rumenal papillae. Work 
investigating this have however failed in substantiating this theory (Ingvartsen et al., 
2001) and found no effects of the VFA-load treatment on postpartum feed intake and 
performance. 
Furthermore in the same study Ingvartsen et al., (2001) compared three feeding strategies in 
early lactation: separate feeding of silage ad libitum and restricted feeding of concentrate 
with a daily increase in allowance of 0.3 kg (C-0.3) or 0.5 kg (C-0.5) up to a total of 10.2 
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kg/d, and a complete diet. It was concluded in that study that one should not increase 
concentrate allowance by more than 0.3 kg daily during early lactation as higher rates 
may increase the risk of rumen acidosis without any production benefits. 
This preliminary report on some aspects of the metabolic study included in the project of 
different feeding strategies in the dry period and early lactation carried out at Stóra Ármót 
in 2002 – 2004 supports the view that there is a large between cow variation which is 
causing problems in evaluating different feeding strategies. The metabolic regulation in 
the transition period is immensely complex and there are still a lot of holes in the 
knowlegde of that mechanism. Recent research in hormonal action shows that not only 
does the concentration of the hormones change but also the sensitivity and response of 
the target organ. 
The results tell us irrespective of treatment that the cows suffer tremendous metabolic 
strain in the early lactation as shown by the very high levels of NEFA and BOHB and at 
the same time low levels of glucose. This is very much in line with previous studies in 
Iceland which have shown a similar picture (Grétar H Harðarson 1980, 1995). This also 
confirms that the Icelandic cow has a high risk of production diseases which is in 
accordance with the limited health records available. The incidence rate of clinical 
ketosis is around 20%, more than 400% higher than in the neighbouring countries. This 
is totally unacceptable and one of the main reasons for moving from component feeding 
to total mixed ration feeding at Stóra Ármót which has been shown to increase DMI by 
up to 24% in early lactation (Ingvartsen et al., 2001). 
 
Heimildir 
Bergman, E.N. 1971. Hyperketonaemia-ketogenesis and ketone body metabolism. J.Dairy Sci. 54. 936-948. 
Bauman, D.E., Currie, W.B., 1980. Partitioning of nutrients during pregnancy and lactation: a review of 
mechanisms involving homeostasis and homeorhesis. J. Dairy Sci. 63, 1514-1529 
Dann, H.M., Varga, G.A., Putnam, D.E., 1999. Improving energy supply to late gestation and early 
postpartum dairy cows. J. Dairy Sci. 82, 1765-1778. 
Drackley, J.K., 1999. Biology of dairy cows during the transition period: The final frontier? J. Dairy Sci. 
82, 2259-2273. 
Grétar Hrafn Harðarson, 1980. An investigation into bovine ketosis in Iceland and its relationship to 
feeding practices. MPhil thesis. University of Edinburgh. 
Grétar Hrafn Harðarson, Þorsteinn Ólafsson og Gunnar Ríkharðsson, 1995. Mismunandi orkufóðrun 
mjólkurkúa í byrjun mjaltaskeiðs. Áhrif fóðrunar á blóðefni. Ráðunautafundur 1995. 103-110. 
Holcomb, C.S., Van Horn, H.H., Head, H.H., Hall, M.B., Wilcox, C.J., 2001. Effects of prepartum dry 
matter intake and forage percentage on postpartum performance of lactating dairy cows. J. Dairy Sci. 
84, 2051-2058. 
Holtenius, K., Agenas, S., Delavaud, C., Chilliard, Y., 2003. Effects of feeding intensity during the dry 
period. 2. Metabolic and hormonal responses. J. Dairy Sci. 86, 883-891. 
Holtenius, P., 1994. The metabolic capacity, a factor of importance for thealth and production in dairy 
cows. XVII Nordic Vet. Congress 26-29 july 1994, Reykjavik, Iceland. 185-189. 
Ingvartsen, K.L., Aaes, O., Andersen, J.B., 2001. Effects of pattern of concentrate allocation in the dry 
period and early lactation on feed intake and lactational performance in dairy cows. Livest. Prod. Sci. 
71, 207-221. 
 102
Ingvartsen, K.L., Andersen, J.B., 2000. Integration of metabolism and intake regulation: a review focusing 
on periparturient animals. J. Dairy Sci. 83, 1573-1597. 
Ingvartsen, K.L., Dewhurst, R.J., Friggens, N.C., 2003a. On the relationship between lactational 
performance and health: is it yield or metabolic imbalance that cause production diseases in dairy 
cattle? A position paper. Livest. Prod. Sci. 73, 277-308. 
Ingvartsen, K.L., Foldager, J., Aaes, O., Andersen, P.H., 1995. Effekt af foderniveau i 24 uger før kælvning 
på foderoptagelse, produktion og stofskifte hos kvier og køer. In: Overgang til laktation. Malkekoens 
fodring og fysiologi under drægtighed og omkring kælvning. Internal Report no. 47, Danish Institute of 
Animal Science, Research Centre Foulum, 60-74. 
Ingvartsen, K.L., Larsen, T., and Berg, P., 2003b. Ændringer og variation i stofskifteparametre - hvad er 
årsagsfaktorerne? In: Internal report 176, Proc. Seminar, May 8, Danish Institute of Agricultural 
Sciences, 71-92. 
Jubb, Kennedy, and Palmer, 1993. Pathology of Domestic Animals 4th ed. Vol. 2, 331-331-336. 
Kronfeld, D.S. 1972. Ketosis in pregnant sheep and lactating cows: a review. Aust. Vet. J., 48, 680-687. 
Kunz, P.L., Blum, J.W., 1985. Effects of different energy intakes before and after calving on food intake, 
performance and blood hormones and metabolites in dairy cows. Anim. Prod. 40, 219-231. 
Liebich, H.G., Mayer, E., Arbitman, R., Dirksen, G., 1982. Strukturelle veränderungen der 
pansenschleimhaut hochproducierender milchkühe von beginn der trockenperiode bis acht wochen post 
partum. In: Proc.12th World Buiatrics Congress, 404-410. 
Mayer, E., Liebich, H.G., Arbitman, R., Hagemeister, H., Dirksen, G., 1986. Nutritially-induced changes in 
the rumenal papillae and in their capacity to absorb short chain fatty acids in high producing dairy 
cows. In: Proc. Fourteenth World Congress on Diseases of Cattle, 806-817. 
Minor, D.J., Trower, S.L., Strang, B.D., Shaver, R.D., Grummer, R.R., 1998. Effects of nonfiber 
carbohydrate and niacin on periparturient metabolic status and lactation of dairy cows. J. Dairy Sci. 81, 
189-200. 
Pullen, D.L., Palmquist, D.L., Emery, R.S., 1989. Effect on days of lactation and methionine hydroxy 
analog on incorporation of plasma fatty acids into plasma triglycerides. J. Dairy Sci. 72, 49-58. 
SAS Institute, 1996. SAS/STAT*Software: Chaanges and Enhancements, Release 6.12. SAS, Cary, NC. 
Schwalm, J.W. and Schultz, L.H. (1976). Relationship of insulin concentration to blood metabolites in the 
dairy cow. J. Dairy Sci. 59, 255-261. 
Steen, A. Holtenius, P. Grønstøl, H. Hoff, B., 1992. Cytologisk finnålaspirasjonsbiopsi av lever – enkel 
metode for diagnose og prognose ved fettlever hos storfe. Norsk Vet tidsskrift. 104, 6, 461-466. 
Theilgaard, P., Friggens, N.C., Sloth, K.H., Ingvartsen, K.L., 2002. The effect of breed, parity and body 
fatness on the lipolytic response of dairy cows. Anim. Sci. 75, 209-220. 
Underwood, J.P., Drackley, J.K., Dahl, G.E., Achtung, T.L., 2003. Responses to epinephrine challenges in 
the peripartal Holstein cow fed two amounts of metabolizable protein in prepartum diets. J. Dairy Sci. 
86, 106 (Abstr.). 
Vandehaar, M.J., Yousif, G., Sharma, B.K., Herdt, T.H., Emery, R.S., Allen, M.S., Liesman, J.S., 1999. 
Effect of energy and protein density of prepartum diets on fat and protein metabolism of dairy cattle in 
the periparturient period. J. Dairy Sci. 82, 1282-1295.