Lipocalin-2 counteracts metabolic dysregulation in obesity and diabetes.

Autor:	Mosialou I; Department of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, NY., Shikhel S; Department of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, NY., Luo N; Department of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, NY., Petropoulou PI; Department of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, NY., Panitsas K; Department of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, NY., Bisikirska B; Department of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, NY., Rothman NJ; Department of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, NY., Tenta R; Department of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, NY., Cariou B; Université de Nantes, Centre Hospitalier Universitaire Nantes, Centre national de la recherche scientifique, Institut national de la santé et de la recherche médicale, l'Institut du thorax, Nantes, France., Wargny M; Université de Nantes, Centre Hospitalier Universitaire Nantes, Centre national de la recherche scientifique, Institut national de la santé et de la recherche médicale, l'Institut du thorax, Nantes, France., Sornay-Rendu E; Institut national de la santé et de la recherche médicale Unités Mixtes de Recherche 1033, Université de Lyon, Hospices Civils de Lyon, Lyon, France., Nickolas T; Department of Medicine Nephrology, Columbia University Medical Center, New York, NY., Rubin M; Department of Medicine Endocrinology, Columbia University Medical Center, New York, NY., Confavreux CB; Institut national de la santé et de la recherche médicale Unités Mixtes de Recherche 1033, Université de Lyon, Hospices Civils de Lyon, Lyon, France., Kousteni S; Department of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, NY.
Jazyk:	angličtina
Zdroj:	The Journal of experimental medicine [J Exp Med] 2020 Oct 05; Vol. 217 (10).
DOI:	10.1084/jem.20191261
Abstrakt:	Regulation of food intake is a recently identified endocrine function of bone that is mediated by Lipocalin-2 (LCN2). Osteoblast-secreted LCN2 suppresses appetite and decreases fat mass while improving glucose metabolism. We now show that serum LCN2 levels correlate with insulin levels and β-cell function, indices of healthy glucose metabolism, in obese mice and obese, prediabetic women. However, LCN2 serum levels also correlate with body mass index and insulin resistance in the same individuals and are increased in obese mice. To dissect this apparent discrepancy, we modulated LCN2 levels in mice. Silencing Lcn2 expression worsens metabolic dysfunction in genetic and diet-induced obese mice. Conversely, increasing circulating LCN2 levels improves metabolic parameters and promotes β-cell function in mouse models of β-cell failure acting as a growth factor necessary for β-cell adaptation to higher metabolic load. These results indicate that LCN2 up-regulation is a protective mechanism to counteract obesity-induced glucose intolerance by decreasing food intake and promoting adaptive β-cell proliferation. Competing Interests: Disclosures: B. Cariou reported grants from Amgen, personal fees from AstraZeneca, personal fees from Gilead, personal fees from Novo Nordisk, grants from Regeneron, grants from Sanofi, and personal fees from Sanofi outside the submitted work. No other disclosures were reported. (© 2020 Mosialou et al.)
Databáze:	MEDLINE
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