Production of Elastin-Derived Peptides Contribute to the Development of Non-Alcoholic Steatohepatitis

Béatrice Romier; Corinne Ivaldi; Hervé Sartelet; Andrea Heinz; Christian E H Schmelzer; Roselyne Garnotel; Alexandre Guillot; Jessica Jonquet; Eric Bertin; Jean-Louis Guéant; Jean-Marc Alberto; Jean-Pierre Bronowicki; Johanne Amoyel; Thinhinane Hocine; Laurent Duca; Pascal Maurice; Amar Bennasroune; Laurent Martiny; Laurent Debelle; Vincent Durlach; Sébastien Blaise

doi:10.2337/db17-0490

Production of Elastin-Derived Peptides Contribute to the Development of Non-Alcoholic Steatohepatitis

Béatrice Romier, Corinne Ivaldi, Hervé Sartelet, Andrea Heinz, Christian E H Schmelzer, Roselyne Garnotel, Alexandre Guillot, Jessica Jonquet, Eric Bertin, Jean-Louis Guéant, Jean-Marc Alberto, Jean-Pierre Bronowicki, Johanne Amoyel, Thinhinane Hocine, Laurent Duca, Pascal Maurice, Amar Bennasroune, Laurent Martiny, Laurent Debelle, Vincent DurlachSébastien Blaise

17 Citations (Scopus)

Abstract

Affecting more than 30% of the Western population, nonalcoholic fatty liver disease (NAFLD) is the most common liver disease and can lead to multiple complications, including nonalcoholic steatohepatitis (NASH), cancer, hypertension, and atherosclerosis. Insulin resistance and obesity are described as potential causes of NAFLD. However, we surmised that factors such as extracellular matrix remodeling of large blood vessels, skin, or lungs may also participate in the progression of liver diseases. We studied the effects of elastin-derived peptides (EDPs), biomarkers of aging, on NAFLD progression. We evaluated the consequences of EDP accumulation in mice and of elastin receptor complex (ERC) activation on lipid storage in hepatocytes, inflammation, and fibrosis development. The accumulation of EDPs induces hepatic lipogenesis (i.e., SREBP1c and ACC), inflammation (i.e., Kupffer cells, IL-1b, and TGF-b), and fibrosis (collagen and elastin expression). These effects are induced by inhibition of the LKB1-AMPK pathway by ERC activation. In addition, pharmacological inhibitors of EDPs demonstrate that this EDP-driven lipogenesis and fibrosis relies on engagement of the ERC. Our data reveal a major role of EDPs in the development of NASH, and they provide new clues for understanding the relationship between NAFLD and vascular aging.

Original language	English
Journal	Diabetes
ISSN	0012-1797
DOIs	https://doi.org/10.2337/db17-0490
Publication status	Published - 1 Aug 2018

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Romier, B., Ivaldi, C., Sartelet, H., Heinz, A., Schmelzer, C. E. H., Garnotel, R., Guillot, A., Jonquet, J., Bertin, E., Guéant, J.-L., Alberto, J.-M., Bronowicki, J.-P., Amoyel, J., Hocine, T., Duca, L., Maurice, P., Bennasroune, A., Martiny, L., Debelle, L., ... Blaise, S. (2018). Production of Elastin-Derived Peptides Contribute to the Development of Non-Alcoholic Steatohepatitis. Diabetes. https://doi.org/10.2337/db17-0490

Romier, B, Ivaldi, C, Sartelet, H, Heinz, A, Schmelzer, CEH, Garnotel, R, Guillot, A, Jonquet, J, Bertin, E, Guéant, J-L, Alberto, J-M, Bronowicki, J-P, Amoyel, J, Hocine, T, Duca, L, Maurice, P, Bennasroune, A, Martiny, L, Debelle, L, Durlach, V & Blaise, S 2018, 'Production of Elastin-Derived Peptides Contribute to the Development of Non-Alcoholic Steatohepatitis', Diabetes. https://doi.org/10.2337/db17-0490

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title = "Production of Elastin-Derived Peptides Contribute to the Development of Non-Alcoholic Steatohepatitis",

abstract = "Affecting more than 30% of the Western population, nonalcoholic fatty liver disease (NAFLD) is the most common liver disease and can lead to multiple complications, including nonalcoholic steatohepatitis (NASH), cancer, hypertension, and atherosclerosis. Insulin resistance and obesity are described as potential causes of NAFLD. However, we surmised that factors such as extracellular matrix remodeling of large blood vessels, skin, or lungs may also participate in the progression of liver diseases. We studied the effects of elastin-derived peptides (EDPs), biomarkers of aging, on NAFLD progression. We evaluated the consequences of EDP accumulation in mice and of elastin receptor complex (ERC) activation on lipid storage in hepatocytes, inflammation, and fibrosis development. The accumulation of EDPs induces hepatic lipogenesis (i.e., SREBP1c and ACC), inflammation (i.e., Kupffer cells, IL-1b, and TGF-b), and fibrosis (collagen and elastin expression). These effects are induced by inhibition of the LKB1-AMPK pathway by ERC activation. In addition, pharmacological inhibitors of EDPs demonstrate that this EDP-driven lipogenesis and fibrosis relies on engagement of the ERC. Our data reveal a major role of EDPs in the development of NASH, and they provide new clues for understanding the relationship between NAFLD and vascular aging.",

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T1 - Production of Elastin-Derived Peptides Contribute to the Development of Non-Alcoholic Steatohepatitis

AU - Romier, Béatrice

AU - Ivaldi, Corinne

AU - Sartelet, Hervé

AU - Heinz, Andrea

AU - Schmelzer, Christian E H

AU - Garnotel, Roselyne

AU - Guillot, Alexandre

AU - Jonquet, Jessica

AU - Bertin, Eric

AU - Guéant, Jean-Louis

AU - Alberto, Jean-Marc

AU - Bronowicki, Jean-Pierre

AU - Amoyel, Johanne

AU - Hocine, Thinhinane

AU - Duca, Laurent

AU - Maurice, Pascal

AU - Bennasroune, Amar

AU - Martiny, Laurent

AU - Debelle, Laurent

AU - Durlach, Vincent

AU - Blaise, Sébastien

PY - 2018/8/1

Y1 - 2018/8/1

N2 - Affecting more than 30% of the Western population, nonalcoholic fatty liver disease (NAFLD) is the most common liver disease and can lead to multiple complications, including nonalcoholic steatohepatitis (NASH), cancer, hypertension, and atherosclerosis. Insulin resistance and obesity are described as potential causes of NAFLD. However, we surmised that factors such as extracellular matrix remodeling of large blood vessels, skin, or lungs may also participate in the progression of liver diseases. We studied the effects of elastin-derived peptides (EDPs), biomarkers of aging, on NAFLD progression. We evaluated the consequences of EDP accumulation in mice and of elastin receptor complex (ERC) activation on lipid storage in hepatocytes, inflammation, and fibrosis development. The accumulation of EDPs induces hepatic lipogenesis (i.e., SREBP1c and ACC), inflammation (i.e., Kupffer cells, IL-1b, and TGF-b), and fibrosis (collagen and elastin expression). These effects are induced by inhibition of the LKB1-AMPK pathway by ERC activation. In addition, pharmacological inhibitors of EDPs demonstrate that this EDP-driven lipogenesis and fibrosis relies on engagement of the ERC. Our data reveal a major role of EDPs in the development of NASH, and they provide new clues for understanding the relationship between NAFLD and vascular aging.

AB - Affecting more than 30% of the Western population, nonalcoholic fatty liver disease (NAFLD) is the most common liver disease and can lead to multiple complications, including nonalcoholic steatohepatitis (NASH), cancer, hypertension, and atherosclerosis. Insulin resistance and obesity are described as potential causes of NAFLD. However, we surmised that factors such as extracellular matrix remodeling of large blood vessels, skin, or lungs may also participate in the progression of liver diseases. We studied the effects of elastin-derived peptides (EDPs), biomarkers of aging, on NAFLD progression. We evaluated the consequences of EDP accumulation in mice and of elastin receptor complex (ERC) activation on lipid storage in hepatocytes, inflammation, and fibrosis development. The accumulation of EDPs induces hepatic lipogenesis (i.e., SREBP1c and ACC), inflammation (i.e., Kupffer cells, IL-1b, and TGF-b), and fibrosis (collagen and elastin expression). These effects are induced by inhibition of the LKB1-AMPK pathway by ERC activation. In addition, pharmacological inhibitors of EDPs demonstrate that this EDP-driven lipogenesis and fibrosis relies on engagement of the ERC. Our data reveal a major role of EDPs in the development of NASH, and they provide new clues for understanding the relationship between NAFLD and vascular aging.

U2 - 10.2337/db17-0490

DO - 10.2337/db17-0490

M3 - Journal article

C2 - 29802129

SN - 0012-1797

JO - Diabetes

JF - Diabetes

ER -

Production of Elastin-Derived Peptides Contribute to the Development of Non-Alcoholic Steatohepatitis

Abstract

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