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Visceral fat: A key mediator of steatohepatitis in metabolic liver disease†
Open accessAbstract
UNLABELLED: Visceral obesity is intimately associated with metabolic disease and adverse health outcomes. However, a direct association between increasing amounts of visceral fat and end-organ inflammation and scarring has not been demonstrated. We examined the association between visceral fat and liver inflammation in patients with nonalcoholic fatty liver disease (NAFLD) to delineate the importance of visceral fat to progressive steatohepatitis and hence the inflammatory pathogenesis of the metabolic syndrome. We undertook a cross-sectional, proof of concept study in 38 consecutive adults with NAFLD at a tertiary liver clinic. All subjects had a complete physical examination, anthropometric assessment, and fasting blood tests on the day of liver biopsy. Abdominal fat volumes were assessed by magnetic resonance imaging within 2 weeks of liver biopsy. The extent of hepatic inflammation and fibrosis augmented incrementally with increases in visceral fat (P < 0.01). For each 1% increase in visceral fat, the odds ratio for increasing liver inflammation and fibrosis was 2.4 (confidence interval [CI]: 1.3-4.2) and 3.5 (CI: 1.7-7.1), respectively. Visceral fat remained an independent predictor of advanced steatohepatitis (odds ratio [OR] 2.1, CI: 1.1-4.2, P = 0.05) and fibrosis (OR 2.9, CI: 1.4-6.3, P = 0.006) even when controlled for insulin resistance and hepatic steatosis. Interleukin-6 (IL-6) levels, which correlated with visceral fat, also independently predicted increasing liver inflammation. Visceral fat was associated with all components of the metabolic syndrome. CONCLUSION: Visceral fat is directly associated with liver inflammation and fibrosis independent of insulin resistance and hepatic steatosis. Visceral fat should therefore be a central target for future interventions in nonalcoholic steatohepatitis and indeed all metabolic disease.
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Cited by
MAFLD: a consensus-driven proposed nomenclature for metabolic associated fatty liver disease
Eslam, M., Sanyal, A. J., George, J., Sanyal, A., Neuschwander-Tetri, B., Tiribelli, C., Kleiner, D. E., Brunt, E., Bugianesi, E., Yki-Järvinen, H., et al. (2020) · Gastroenterology · doi:10.1053/j.gastro.2019.11.312 · Cited by 3,286
Self-citationRinella, M. E., Neuschwander-Tetri, B. A., Siddiqui, M. S., Abdelmalek, M. F., Caldwell, S., Barb, D., Kleiner, D. E., & Loomba, R. (2023) · Hepatology · doi:10.1097/hep.0000000000000323 · Cited by 2,667
Evolution of inflammation in nonalcoholic fatty liver disease: The multiple parallel hits hypothesis
Tilg, H., & Moschen, A. R. (2010) · Hepatology · doi:10.1002/hep.24001 · Cited by 2,548
Mechanisms and disease consequences of nonalcoholic fatty liver disease
Loomba, R., Friedman, S. L., & Shulman, G. I. (2021) · Cell · doi:10.1016/j.cell.2021.04.015 · Cited by 2,002
Treatment of NAFLD with diet, physical activity and exercise
Romero-Gómez, M., Zelber-Sagi, S., & Trenell, M. (2017) · Journal of Hepatology · doi:10.1016/j.jhep.2017.05.016 · Cited by 1,347
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Metadata
- Authors
- van der Poorten, D., Milner, K., Hui, J., Hodge, A., Trenell, M. I., Kench, J. G., London, R., Peduto, T., Chisholm, D. J., & George, J.
- Venue
- Hepatology
- Published
- 2008-08
- Volume
- 48
- Issue
- 2
- Pages
- 449-457
- ISSN
- 0270-9139 (ISSN-L)
- OpenAlex
- W2033665384
- Cited by
- 607
- References
- 35
- FWCI
- 23.87
- Type
- journal article
- Language
- en
- Open access
- bronze
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- van der Poorten, D., Milner, K., Hui, J., Hodge, A., Trenell, M. I., Kench, J. G., London, R., Peduto, T., Chisholm, D. J., & George, J. (2008). Visceral fat: A key mediator of steatohepatitis in metabolic liver disease†. Hepatology. https://doi.org/10.1002/hep.22350
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