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Título

Involvement of protein tyrosine phosphatases and inflammation in hypothalamic insulin resistance associated with ageing: Effect of caloric restriction

Autor García-Frutos, Miriam; Fernández-Agulló, T.; Carrascosa, José M.; Horrillo, Daniel; Barrús, María Teresa; Sierra, Johanna; Ros, Manuel
Palabras clave Obesity
Ageing
Caloric restriction
Inflammation
Insulin resistance
Hypothalamus
Fecha de publicación 2012
EditorElsevier
Citación Mechanisms of Ageing and Development 133: 489- 497 (2012)
ResumenAged Wistar rats present central insulin resistance associated with ageing. Several steps of the insulin signaling pathway have been described to be impaired in aged rats at hypothalamic level. In the present article we have explored possible alterations in protein tyrosine phosphatases (PTPs) involved in insulin receptor dephosphorylation, as well as pro-inflammatory pathways and serine kinases such as inhibitory kappa β kinase-nuclear factor kappa-B (IKKβ-NFκB), p38 mitogen-activated protein kinase (p38) and protein kinase C θ (PKCθ) that may also be involved in the decreased insulin signaling during ageing. We detected that ageing brings about a specific increase in insulin receptor tyrosine phosphatase activity and PTP1B serine phosphorylation. Increased association of PTP1B and leukocyte common antigen-related tyrosine protein phosphatase (LAR) with insulin receptor was also observed in hypothalamus from aged rats. Besides these mechanisms, increased activation of the IKKβ-NFκB pathway, p38 and PKCθ serine/threonine kinases were also detected. These data contribute to explain the hypothalamic insulin resistance associated with ageing. Caloric restriction ameliorates most of the effects of ageing on the above mentioned increases in PTPs and serine/threonine kinases activities and points to age-associated adiposity and inflammation as key factors in the development of age-associated insulin resistance. © 2012 Elsevier Ireland Ltd.
URI http://hdl.handle.net/10261/113639
DOI10.1016/j.mad.2012.06.001
Identificadoresdoi: 10.1016/j.mad.2012.06.001
issn: 0047-6374
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