Peroxisome Proliferator-Activated Receptor γ 2 Modulates Late-Pregnancy Homeostatic Metabolic Adaptations

Vivas, Yurena; Díez-Hochleitner, Monica; Izquierdo‐Lahuerta, Adriana; Corrales, Patricia; Horrillo, Daniel; Velasco, Ismael; Martínez-García, Cristina; Campbell, Mark; Sevillano, Julio; Ricote, Mercedes; Ros, Manuel; Ramos, M. Teresa; Medina-Gómez, Gema

doi:10.2119/molmed.2015.00262

Cited by 15 publications

(15 citation statements)

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“…In pregnant mouse models, the association between a decrease in PPARγ expression, exacerbated lipolysis in the AT [ 70 ], and the subcutaneous AT dysfunction has been reported. In agreement with this, we have shown that genetic ablation of PPARγ2 in pregnant mice is associated with poor AT expandability and the worsening of insulin resistance [ 71 ]. The contribution of PPARγ2 is also important for the process of pancreatic β-cell mass expansion and adaptation in murine models of MetS [ 50 , 71 , 72 ].…”

Section: Ppars and Pregnancysupporting

confidence: 67%

PPARs and Metabolic Disorders Associated with Challenged Adipose Tissue Plasticity

Corrales

Vidal-Puig

Medina‐Gómez

2018

IJMS

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123

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Peroxisome proliferator-activated receptors (PPARs) are members of a family of nuclear hormone receptors that exert their transcriptional control on genes harboring PPAR-responsive regulatory elements (PPRE) in partnership with retinoid X receptors (RXR). The activation of PPARs coordinated by specific coactivators/repressors regulate networks of genes controlling diverse homeostatic processes involving inflammation, adipogenesis, lipid metabolism, glucose homeostasis, and insulin resistance. Defects in PPARs have been linked to lipodystrophy, obesity, and insulin resistance as a result of the impairment of adipose tissue expandability and functionality. PPARs can act as lipid sensors, and when optimally activated, can rewire many of the metabolic pathways typically disrupted in obesity leading to an improvement of metabolic homeostasis. PPARs also contribute to the homeostasis of adipose tissue under challenging physiological circumstances, such as pregnancy and aging. Given their potential pathogenic role and their therapeutic potential, the benefits of PPARs activation should not only be considered relevant in the context of energy balance-associated pathologies and insulin resistance but also as potential relevant targets in the context of diabetic pregnancy and changes in body composition and metabolic stress associated with aging. Here, we review the rationale for the optimization of PPAR activation under these conditions.

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Section: Ppars and Pregnancysupporting

confidence: 67%

PPARs and Metabolic Disorders Associated with Challenged Adipose Tissue Plasticity

Corrales

Vidal-Puig

Medina‐Gómez

2018

IJMS

Self Cite

123

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“…The inflammatory burden resulting from a single immunocompromised state, such as pregnancy, can be distinctively altered when compounded with chronic inflammation. Elevated adiposity and abnormal glucose metabolism prior to—or during—pregnancy can limit the ability to accommodate fetal demands and are associated with unique and targeted changes in inflammation during gestation ( 35 – 37 ). The inflammation present in utero can be transferred from mother to fetus ( 38 ).…”

Section: Introductionmentioning

confidence: 99%

Maternal Diet, Metabolic State, and Inflammatory Response Exert Unique and Long-Lasting Influences on Offspring Behavior in Non-Human Primates

et al. 2018

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Nutritional status influences brain health and gestational exposure to metabolic disorders (e.g. obesity and diabetes) increases the risk of neuropsychiatric disorders. The aim of the present study was to further investigate the role of maternal Western-style diet (WSD), metabolic state, and inflammatory factors in the programming of Japanese macaque offspring behavior. Utilizing structural equation modeling, we investigated the relationships between maternal diet, prepregnancy adiposity, third trimester insulin response, and plasma cytokine levels on 11-month-old offspring behavior. Maternal WSD was associated with greater reactive and ritualized anxiety in offspring. Maternal adiposity and third trimester macrophage-derived chemokine (MDC) exerted opposing effects on offspring high-energy outbursts. Elevated levels of this behavior were associated with low maternal MDC and increased prepregnancy adiposity. This is the first study to show that maternal MDC levels influence offspring behavior. We found no evidence suggesting maternal peripheral inflammatory response mediated the effect of maternal diet and metabolic state on aberrant offspring behavior. Additionally, the extent of maternal metabolic impairment differentially influenced chemokine response. Elevated prepregnancy adiposity suppressed third trimester chemokines, while obesity-induced insulin resistance augmented peripheral chemokine levels. WSD also directly increased maternal interleukin-12. This is the first non-human primate study to delineate the effects of maternal diet and metabolic state on gestational inflammatory environment and subsequent offspring behavior. Our findings give insight to the complex mechanisms by which diet, metabolic state, and inflammation during pregnancy exert unique influences on offspring behavioral regulation.

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“…Así, se acumula grasa en otros tejidos como el músculo y el hígado, entre otros, dando lugar al fenómeno tóxico conocido como lipotoxicidad. Además, conforme se expande el tejido adiposo, este tejido acumula cada vez más grasa y dispara mecanismos inflamatorios y de infiltración de células del sistema inmunitario denominadas macrófagos 6 . Esta respuesta inflamatoria exagerada en el tejido adiposo y en la placenta conduce a un estado crónico de inflamación que puede originar incluso la disminución de la transferencia de oxígeno desde la madre al feto a través de la placenta.…”

Section: Discussionunclassified

Adaptaciones metabólicas maternas durante la gestación: el problema del sobrepeso y la obesidad

Gómez¹

2017

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Adaptaciones metabólicas maternas durante la gestación: el problema del sobrepeso y la obesidad. es/ES/divulgacionciencia-para-todos_10/la-ciencia-alalcance-de-la-mano-articulos-dedivulgacion_29Resumen Durante la gestación tienen lugar adaptaciones metabólicas maternas para aumentar la sensibilidad a la insulina y mantener un adecuado nivel de glucosa para transferirse al feto.Tanto el sobrepeso como la obesidad durante el embarazo pueden generar el desarrollo de diabetes gestacional y futuros problemas metabólicos tanto en la madre como en la descendencia. SummaryDuring pregnancy, maternal metabolic adaptations occur to increase insulin sensitivity and to maintain an adequate glucose level to be transferred to the fetus. Overweight and obesity during pregnancy may lead to the development of gestational diabetes and future metabolic problems in both mother and offspring.La gestación tiene lugar desde la implantación del cigoto en el útero hasta el momento del parto. Desde el punto de vista metabólico, durante la gestación existen dos etapas bien diferenciadas: 1) en los dos primeros tercios, predomina una fase denominada anabólica, en la que la gestante aumenta su peso corporal debido a una lipogénesis activa que permite el acúmulo de tejido adiposo; y 2) en el último tercio, el metabolismo materno se invierte y entra en una fase denominada catabólica, en la que tiene lugar la movilización de la reservas maternas a través de la placenta para asegurar el correcto crecimiento del feto 1 . Es importante destacar que durante estas dos fases existen variaciones en las hormonas gestacionales y placentarias, que tienen efecto en la concentración y la sensibilidad a la insulina para dar lugar a unos niveles de glucosa maternos adecuados. Esta glucosa será proporcionada al feto a través de la placenta durante la gestación para el adecuado embarazo a término. Por tanto, durante el embarazo, la madre presenta una mayor acumulación de tejido adiposo, además de presentar hiperinsulinemia y resistencia a la insulina. Existen evidencias científicas que sugieren un papel importante de los receptores nucleares PPARγ, que regulan la sensibilidad a la insulina. Los receptores PPARγ tienen una función clave en el proceso de la adipogénesis o formación del tejido adiposo y en el almacenamiento de lípidos. También mejoran la sensibilidad a insulina periférica gracias a que disminuyen los ácidos grasos en la circulación e impiden que éstos se acumulen en otros tejidos. Durante el embarazo, el receptor PPARγ genera modificaciones a nivel de la célula-βeta pancreática, la célula del páncreas que produce insulina, aumentando no sólo en su tamaño sino también en número, para poder aumentar la secreción de insulina materna. También se produce un

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Peroxisome Proliferator-Activated Receptor γ 2 Modulates Late-Pregnancy Homeostatic Metabolic Adaptations

Cited by 15 publications

References 40 publications

PPARs and Metabolic Disorders Associated with Challenged Adipose Tissue Plasticity

PPARs and Metabolic Disorders Associated with Challenged Adipose Tissue Plasticity

Maternal Diet, Metabolic State, and Inflammatory Response Exert Unique and Long-Lasting Influences on Offspring Behavior in Non-Human Primates

Adaptaciones metabólicas maternas durante la gestación: el problema del sobrepeso y la obesidad

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