Nutritional model of steatohepatitis and metabolic syndrome in the Ossabaw miniature swine

Lydia Lee, Mouhamad Alloosh, Romil Saxena, William Van Alstine, Bruce A. Watkins, James E. Klaunig, Michael Sturek, Naga Chalasani

Research output: Contribution to journalArticle

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Abstract

Miniature pigs residing in the Ossabaw Island (Ossabaw pigs) exhibit a thrifty genotype, and when fed a high-calorie diet they consistently develop metabolic syndrome defined by obesity, insulin resistance, hypertension, and dyslipidemia. We conducted a study to induce steatohepatitis in Ossabaw pigs by dietary manipulation. Pigs were fed standard chow (controls, n = 15), high-fructose diet (20% kcal from fructose and 10.5% kcal from fat) (fructose group, n = 9), atherogenic diet (20% kcal from fructose and 46% kcal from fat and 2% cholesterol and 0.7% cholate by weight) (atherogenic diet group, n = 13), and modified atherogenic diet (different source of fat and higher protein but lower choline content) (M-Ath diet group, n = 7). All animals were sacrificed at 24 weeks after dietary intervention. The high-fructose group had significant weight gain, hypertension, and insulin resistance but showed normal liver histology. The atherogenic diet group had metabolic syndrome and abnormal liver histology consisting of significant microvesicular steatosis and fatty Kupffer cells but no ballooning or fibrosis. The M-Ath diet group developed severe metabolic syndrome and markedly abnormal liver histology with macrovesicular and microvesicular steatosis, fatty Kupffer cells, extensive hepatocyte ballooning, and pericellular/perisinusoidal fibrosis. Compared with controls, the M-Ath diet group had significantly lower serum adiponectin but higher serum leptin and tumor necrosis factor (TNF) levels and higher hepatic triglyceride and malondialdehyde levels. Conclusion: Ossabaw pigs fed a modified atherogenic diet develop severe metabolic syndrome and abnormal liver histology with close resemblance to human nonalcoholic steatohepatitis (NASH).

Original languageEnglish
Pages (from-to)56-67
Number of pages12
JournalHepatology
Volume50
Issue number1
DOIs
StatePublished - 2009

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Atherogenic Diet
Miniature Swine
Fatty Liver
Fructose
Swine
Diet
Histology
Liver
Kupffer Cells
Fats
Insulin Resistance
Fibrosis
Cholates
Hypertension
Adiponectin
Dyslipidemias
Leptin
Choline
Malondialdehyde
Serum

ASJC Scopus subject areas

  • Hepatology
  • Medicine(all)

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Nutritional model of steatohepatitis and metabolic syndrome in the Ossabaw miniature swine. / Lee, Lydia; Alloosh, Mouhamad; Saxena, Romil; Van Alstine, William; Watkins, Bruce A.; Klaunig, James E.; Sturek, Michael; Chalasani, Naga.

In: Hepatology, Vol. 50, No. 1, 2009, p. 56-67.

Research output: Contribution to journalArticle

Lee, Lydia ; Alloosh, Mouhamad ; Saxena, Romil ; Van Alstine, William ; Watkins, Bruce A. ; Klaunig, James E. ; Sturek, Michael ; Chalasani, Naga. / Nutritional model of steatohepatitis and metabolic syndrome in the Ossabaw miniature swine. In: Hepatology. 2009 ; Vol. 50, No. 1. pp. 56-67.
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