Key questions and answers about pregnancy-associated plasma protein-A

Conover, Cheryl A.

doi:10.1016/j.tem.2012.02.008

Cited by 139 publications

(141 citation statements)

References 94 publications

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“…Because these whole body glucose tolerance and insulin sensitivity tests reflect overall contributions of skeletal muscle, liver, and brain as well as all adipose tissue, we looked at fat depot-specific IGF-I/insulin receptor signaling via phosphorylation of AKT on Ser 47 (8,11). After 20 wk on HFD, basal phosphorylated AKT (pAKT) was twofold greater in inguinal vs. mesenteric fat of WT mice.…”

mentioning

confidence: 99%

Preferential impact of pregnancy-associated plasma protein-A deficiency on visceral fat in mice on high-fat diet

Conover

Harstad

Tchkonia

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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Conover CA, Harstad SL, Tchkonia T, Kirkland JL. Preferential impact of pregnancy-associated plasma protein-A deficiency on visceral fat in mice on high-fat diet. Am J Physiol Endocrinol Metab 305: E1145-E1153, 2013. First published September 17, 2013 doi:10.1152/ajpendo.00405.2013.-Accumulation of visceral fat, more so than subcutaneous fat, is strongly associated with severe metabolic complications. However, the factors regulating depot-specific adipogenesis are poorly understood. In this study, we show differential expression of pregnancy-associated plasma protein-A (PAPP-A), a secreted regulator of local insulin-like growth factor (IGF) action, in adipose tissue of mice. PAPP-A mRNA expression was fivefold higher in visceral (mesenteric) fat compared with subcutaneous (inguinal, subscapular), perirenal, and brown fat of mice. To investigate the possible role of depot-specific PAPP-A expression in fat accumulation, wild-type (WT) and PAPP-A knockout (KO) mice were fed a high-fat diet (HFD) for up to 20 wk. Adipocyte size increased in subcutaneous and perirenal depots similarly in WT and PAPP-A KO mice. However, fat cell size and in vivo lipid uptake were significantly reduced in mesenteric fat of PAPP-A KO compared with WT mice. After 20 wk on HFD, phosphorylation of AKT, a downstream signaling intermediate of IGF-I and insulin receptor activation, was significantly decreased by 50% in mesenteric compared with subcutaneous fat in WT mice, but was significantly increased threefold in mesenteric compared with subcutaneous fat in PAPP-A KO mice. This appeared to be because of enhanced insulinstimulated signaling in mesenteric fat of PAPP-A KO mice. These data establish fat depot-specific expression of PAPP-A and indicate preferential impact of PAPP-A deficiency on visceral fat in the mouse that is associated with enhanced insulin receptor signaling. Thus, PAPP-A may be a potential target for treatment and/or prevention strategies for visceral obesity and related morbidities.

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mentioning

confidence: 99%

Preferential impact of pregnancy-associated plasma protein-A deficiency on visceral fat in mice on high-fat diet

Conover

Harstad

Tchkonia

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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“…Esta metaloproteasa escinde especialmente a IGFBP4 y se discute su actividad sobre IGFBP2 y 5 (Spicer, 2004). Además, se conocen otras metaloproteasas, las calicreínas, que están presentes en el LF y pueden degradar otras IGFBPs, incluyendo a IGFBP2, 3 y 5 (Mazerbourg et al, 2001;Conover, 2012).…”

Section: Descripción Del Sistema Igfunclassified

“…Por un lado, para el clivaje de la IGFBP4 es necesaria la presencia de IGF1 o 2, de esta manera, la IGFBP4 se une a IGF con alta afinidad y previene su interacción con los receptores de la superficie de la célula blanco (Qin et al 2000;Laursen et al 2001). Sólo cuando la IGFBP4 está unida al IGF, se convierte en sustrato para PAPP-A (Conover, 2012). En contraste, para que la PAPP-A clive a la IGFBP5 no se requiere la presencia de IGF, aunque la acción mejora ligeramente en presencia del ligando (Aad et al, 2006;Gaidamauskas et al, 2013).…”

Section: Control De La Biodisponibilidad De Igfs En El Ovariounclassified

Participación del sistema IGF en la patogenia de la enfermedad quística bovina

Rodríguez¹,

Salvetti²,

Ortega³

et al. 2016

FAVE Cs Vet

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La enfermedad quística ovárica (COD) es una de las principales causas de falla reproductiva y de infertilidad, y constituye uno de los de los trastornos reproductivos más frecuentes en vacas lecheras de alta producción. El desarrollo de esta enfermedad está asociado a un desequilibrio en el eje hipotalámico-hipofisario-gonadal en el cual factores endocrinos, entre ellos el sistema de factores de crecimiento análogos a insulina (IGF), participan en el desarrollo folicular, diferenciación celular y la secreción de hormonas ováricas. Considerando al sistema IGF como un importante regulador del crecimiento y funcionalidad folicular, evaluamos la participación de componentes del sistema IGF en el desarrollo de la COD. Las alteraciones en diferentes componentes del sistema IGF que podrían afectar al normal funcionamiento del ovario participando en el desarrollo de la COD en bovinos.

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“…We propose PAPP-A as another regulatory component, enhancing local IGF-I bioavailability. PAPP-A expression has been shown to increase in response to tissue injury (Conover 2012). Moreover, PAPP-A expression is potently stimulated by macrophagederived proinflammatory cytokines, tumor necrosis factor-α and interleukin-1β, in fibroblasts and vascular smooth muscle cells, and by transforming growth factor-β in human osteoblasts (Conover et al 2006, Resch et al 2004, Ortiz et al 2003.…”

Section: Proposed Role Of Igf-i and Papp-a In Diabetic Nephropathymentioning

confidence: 99%

Mice deficient in PAPP-A show resistance to the development of diabetic nephropathy

Mader¹,

Resch²,

McLean³

et al. 2014

EJEA

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We investigated pregnancy-associated plasma protein-A (PAPP-A) in diabetic nephropathy. Normal human kidney showed specific staining for PAPP-A in glomeruli, and this staining was markedly increased in diabetic kidney. To assess possible contribution of PAPP-A in the development of diabetic nephropathy, we induced diabetes with streptozotocin in 14-month-old wild-type (WT) and PAPP-A knock-out (KO) mice. Renal histopathology was evaluated after four months of stable hyperglycemia. Kidneys from diabetic WT mice showed multiple abnormalities including thickening of Bowman's capsule (100% of mice), increased glomerular size (80% of mice), tubule dilation (80% of mice), and mononuclear cell infiltration (90% of mice). Kidneys of age-matched non-diabetic WT mice had similar evidence of tubule dilation and mononuclear cell infiltration as diabetic WT mice indicating that these changes were predominantly age-related.

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Key questions and answers about pregnancy-associated plasma protein-A

Cited by 139 publications

References 94 publications

Preferential impact of pregnancy-associated plasma protein-A deficiency on visceral fat in mice on high-fat diet

Preferential impact of pregnancy-associated plasma protein-A deficiency on visceral fat in mice on high-fat diet

Participación del sistema IGF en la patogenia de la enfermedad quística bovina

Mice deficient in PAPP-A show resistance to the development of diabetic nephropathy

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