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Am J Transl Res 2013;5(5):543-554
Original Article
Malnutrition induces gut atrophy and increases hepatic fat infiltration:
studies in a pig model of childhood malnutrition
Mikkel Lykke, Anne-Louise Hother, Christian F Hansen, Henrik Friis, Christian Mølgaard, Kim F Michaelsen, André
Briend, Torben Larsen, Per T Sangild, Thomas Thymann
Department of Nutrition, Exercise and Sports, University of Copenhagen, 30 Rolighedsvej, DK-1958
Frederiksberg C, Denmark; Department of Large Animal Sciences, University of Copenhagen, 2 Grønnegårdsvej,
DK-1870 Frederiksberg C, Denmark; Department of International Health, University of Tampere, Tampere,
Finland; Department of Animal Science, Aarhus University, AU Foulum, Blichers Allé 20, DK-8830 Tjele, Denmark
Received June 16, 2013; Accepted July 25, 2013; Epub August 15, 2013; Published August 30, 2013
Abstract: Childhood malnutrition is a problem in developing countries, and pathological changes in digestive
organs such as the intestine and liver are poorly understood. An animal model to study the progression of severe
acute malnutrition could elucidate pathological changes in the intestine and liver. We sought to characterize
growth and clinical changes during malnutrition related to structural and functional indices in the intestine and
liver. Newly weaned piglets were given ad libitum access to a maize flour diet (MAIZE, n=9) or a nutritionally
optimized reference diet (REFERENCE, n=12) for 7 weeks. Growth, hematology and clinical biochemistry where
recorded weekly. After 7 weeks, the MAIZE pigs had lower body weights than the REF pigs (8.3 kg vs. 32.4 kg,
P<0.001), indicating severe stunting and moderate to severe wasting. This was paralleled by lower values for
hematocrit, hemoglobin and mean cell volume in MAIZE vs. REFERENCE (P<0.01), indicating anemia. Although
the observed temporal changes in MAIZE were associated with atrophy of the small intestinal mucosa (P<0.001),
digestive enzyme activity was only marginally reduced. Serum alanine aminotransferase, bilirubin and albumin
were increased in the MAIZE pigs (P<0.001), and the liver had a vacuolated appearance and tendency toward
increased triglyceride content (P=0.054). We conclude that liver and intestinal indices are compromised during
malnutrition and are associated with temporal changes in growth and hematological and biochemical endpoints.
The pig model is relevant for malnourished infants and can act as a valuable tool for understanding the
pathophysiology of malnutrition. (AJTR1306003).
Keywords: Malnutrition, pig, gut, liver, animal model
Address correspondence to: Dr. Thomas Thymann, Department of Nutrition, Exercise and Sports, Uni-versity of
Copenhagen, 30 Rolighedsvej, DK-1958 Frederiksberg C, Denmark. Tel: +45 3533 2622; Fax: +45 3533 2483;
E-mail: ttn@life.ku.dk
Original Article
Malnutrition induces gut atrophy and increases hepatic fat infiltration:
studies in a pig model of childhood malnutrition
Mikkel Lykke, Anne-Louise Hother, Christian F Hansen, Henrik Friis, Christian Mølgaard, Kim F Michaelsen, André
Briend, Torben Larsen, Per T Sangild, Thomas Thymann
Department of Nutrition, Exercise and Sports, University of Copenhagen, 30 Rolighedsvej, DK-1958
Frederiksberg C, Denmark; Department of Large Animal Sciences, University of Copenhagen, 2 Grønnegårdsvej,
DK-1870 Frederiksberg C, Denmark; Department of International Health, University of Tampere, Tampere,
Finland; Department of Animal Science, Aarhus University, AU Foulum, Blichers Allé 20, DK-8830 Tjele, Denmark
Received June 16, 2013; Accepted July 25, 2013; Epub August 15, 2013; Published August 30, 2013
Abstract: Childhood malnutrition is a problem in developing countries, and pathological changes in digestive
organs such as the intestine and liver are poorly understood. An animal model to study the progression of severe
acute malnutrition could elucidate pathological changes in the intestine and liver. We sought to characterize
growth and clinical changes during malnutrition related to structural and functional indices in the intestine and
liver. Newly weaned piglets were given ad libitum access to a maize flour diet (MAIZE, n=9) or a nutritionally
optimized reference diet (REFERENCE, n=12) for 7 weeks. Growth, hematology and clinical biochemistry where
recorded weekly. After 7 weeks, the MAIZE pigs had lower body weights than the REF pigs (8.3 kg vs. 32.4 kg,
P<0.001), indicating severe stunting and moderate to severe wasting. This was paralleled by lower values for
hematocrit, hemoglobin and mean cell volume in MAIZE vs. REFERENCE (P<0.01), indicating anemia. Although
the observed temporal changes in MAIZE were associated with atrophy of the small intestinal mucosa (P<0.001),
digestive enzyme activity was only marginally reduced. Serum alanine aminotransferase, bilirubin and albumin
were increased in the MAIZE pigs (P<0.001), and the liver had a vacuolated appearance and tendency toward
increased triglyceride content (P=0.054). We conclude that liver and intestinal indices are compromised during
malnutrition and are associated with temporal changes in growth and hematological and biochemical endpoints.
The pig model is relevant for malnourished infants and can act as a valuable tool for understanding the
pathophysiology of malnutrition. (AJTR1306003).
Keywords: Malnutrition, pig, gut, liver, animal model
Address correspondence to: Dr. Thomas Thymann, Department of Nutrition, Exercise and Sports, Uni-versity of
Copenhagen, 30 Rolighedsvej, DK-1958 Frederiksberg C, Denmark. Tel: +45 3533 2622; Fax: +45 3533 2483;
E-mail: ttn@life.ku.dk
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