Classically activated macrophages (M1) secrete proinflammatory cytokine and are predominant in obese adipose tissue. M2 macrophages, prevalent in lean adipose tissue, are induced by IL-13 and IL-4, mainly secreted by Th2 lymphocytes, and produce the anti-inflammatory cytokine IL-10. ITCH is a ubiquitously expressed E3 ubiquitin ligase involved in T-cell differentiation and in a wide range of inflammatory pathways. ITCH downregulation in lymphocytes causes aberrant Th2 differentiation. To investigate the role of Th2/M2 polarization in obesity-related inflammation and insulin resistance, we compared wild-type and Itch(-/-) mice in a context of diet-induced obesity (high-fat diet [HFD]). When subjected to HFD, Itch(-/-) mice did not show an increase in body weight or insulin resistance; calorimetric analysis suggested an accelerated metabolism. The molecular analysis of metabolically active tissue revealed increased levels of M2 markers and genes involved in fatty acid oxidation. Histological examination of livers from Itch(-/-) mice suggested that ITCH deficiency protects mice from obesity-related nonalcoholic fatty liver disease. We also found a negative correlation between ITCH and M2 marker expression in human adipose tissues. Taken together, our data indicate that ITCH E3 ubiquitin ligase deficiency protects from the metabolic disorder caused by obesity.

Marino, A., Menghini, R., Fabrizi, M., Casagrande, V., Mavilio, M., Stoehr, R., et al. (2014). ITCH deficiency protects from diet-induced obesity. DIABETES, 63(2), 550-561 [10.2337/db13-0802].

ITCH deficiency protects from diet-induced obesity

MENGHINI, ROSSELLA;CANDI, ELEONORA;MAURIELLO, ALESSANDRO;MELINO, GENNARO;LAURO, RENATO;FEDERICI, MASSIMO
2014-02-01

Abstract

Classically activated macrophages (M1) secrete proinflammatory cytokine and are predominant in obese adipose tissue. M2 macrophages, prevalent in lean adipose tissue, are induced by IL-13 and IL-4, mainly secreted by Th2 lymphocytes, and produce the anti-inflammatory cytokine IL-10. ITCH is a ubiquitously expressed E3 ubiquitin ligase involved in T-cell differentiation and in a wide range of inflammatory pathways. ITCH downregulation in lymphocytes causes aberrant Th2 differentiation. To investigate the role of Th2/M2 polarization in obesity-related inflammation and insulin resistance, we compared wild-type and Itch(-/-) mice in a context of diet-induced obesity (high-fat diet [HFD]). When subjected to HFD, Itch(-/-) mice did not show an increase in body weight or insulin resistance; calorimetric analysis suggested an accelerated metabolism. The molecular analysis of metabolically active tissue revealed increased levels of M2 markers and genes involved in fatty acid oxidation. Histological examination of livers from Itch(-/-) mice suggested that ITCH deficiency protects mice from obesity-related nonalcoholic fatty liver disease. We also found a negative correlation between ITCH and M2 marker expression in human adipose tissues. Taken together, our data indicate that ITCH E3 ubiquitin ligase deficiency protects from the metabolic disorder caused by obesity.
feb-2014
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/49 - SCIENZE TECNICHE DIETETICHE APPLICATE
Settore BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA
English
Con Impact Factor ISI
Ubiquitin-Protein Ligases; Obesity; Animals; Humans; Adipose Tissue, White; Mice; Adipose Tissue, Brown; Receptors, Cell Surface; Mice, Knockout; Lectins, C-Type; Mannose-Binding Lectins; Macrophages, Peritoneal; Liver; Gene Expression Regulation; Dietary Fats; Biological Markers
FLORINASH
Marino, A., Menghini, R., Fabrizi, M., Casagrande, V., Mavilio, M., Stoehr, R., et al. (2014). ITCH deficiency protects from diet-induced obesity. DIABETES, 63(2), 550-561 [10.2337/db13-0802].
Marino, A; Menghini, R; Fabrizi, M; Casagrande, V; Mavilio, M; Stoehr, R; Candi, E; Mauriello, A; Moreno Navarrete, J; Gómez Serrano, M; Peral, B; Melino, G; Lauro, R; Fernandez Real, J; Federici, M
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/89843
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