Elevated n-3/n-6 PUFA ratio in early life diet reverses adverse intrauterine kidney programming in female rats

Voggel, Jenny; Fink, G. D.; Zelck, Magdalena; Wohlfarth, Maria; Post, Julia M.; Bîndilă, Laura; Rauh, Manfred; Amann, Kerstin; Alcázar, Miguel A. Alejandre; Dötsch, Jörg; Nüsken, Kai-Dietrich; Nüsken, Eva

doi:10.1016/j.jlr.2022.100283

Cited by 4 publications

(3 citation statements)

References 89 publications

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“…The glomerular proteome was analyzed by a mass spectrometry system containing a Q ExactivePlusOrbitrap and an EASY nLC 1000 with a C18 analytical column. The detailed procedure has been described elsewhere 22 . Statistical analysis was performed with the Perseus software (version 1.5.5.3) 23 and the package limma in R 24 .…”

Section: Methodsmentioning

confidence: 99%

The effect of mycophenolate mofetil on podocytes in nephrotoxic serum nephritis

Hackl,

Nüsken,

Voggel

et al. 2023

Sci Rep

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Mycophenolate mofetil (MMF) is applied in proteinuric kidney diseases, but the exact mechanism of its effect on podocytes is still unknown. Our previous in vitro experiments suggested that MMF can ameliorate podocyte damage via restoration of the Ca2+-actin cytoskeleton axis. The goal of this study was to characterize podocyte biology during MMF treatment in nephrotoxic serum (NTS) nephritis (NTN). NTN was induced in three-week old wild-type mice. On day 3, half of the mice were treated with MMF (100 mg/kgBW/d p.o.) for one week. On day 10, we performed proteomic analysis of glomeruli as well as super-resolution imaging of the slit diaphragm. For multiphoton imaging of Ca2+ concentration ([Ca2+]i), the experimental design was repeated in mice expressing podocyte-specific Ca2+ sensor. MMF ameliorated the proteinuria and crescent formation induced by NTS. We identified significant changes in the abundance of proteins involved in Ca2+ signaling and actin cytoskeleton regulation, which was further confirmed by direct [Ca2+]i imaging in podocytes showing decreased Ca2+ levels after MMF treatment. This was associated with a tendency to restoration of podocyte foot process structure. Here, we provide evidence that MPA has a substantial direct effect on podocytes. MMF contributes to improvement of [Ca2+]i and amelioration of the disorganized actin cytoskeleton in podocytes. These data extend the knowledge of direct effects of immunosuppressants on podocytes that may contribute to a more effective treatment of proteinuric glomerulopathies with the least possible side effects.

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Section: Methodsmentioning

confidence: 99%

The effect of mycophenolate mofetil on podocytes in nephrotoxic serum nephritis

Hackl,

Nüsken,

Voggel

et al. 2023

Sci Rep

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“…Postnatal supplementation of ω-3 PUFA to IUGR-born offspring is also effective in improving metabolic deficits. For example, IUGR-born rats exhibited 50% reductions in circulating triglycerides and 33% reductions in blood urea nitrogen when nursing foster dams that were fed diets high in ω-3 PUFA (i.e., supplemented to offspring via milk) ( Voggel et al, 2022 ). Likewise, directly feeding ω-3 PUFA-enriched diets or supplementing ω-3 PUFA-rich fish oil to IUGR-born juvenile rats partially resolved their hyperlipidemia and reduced their adiposity ( Wyrwoll et al, 2006 ; Bringhenti et al, 2011 ; Chen et al, 2016 ; Chicco et al, 2016 ).…”

Section: Mitigating the Impact Of Iugr With ω-3 Pufamentioning

confidence: 99%

Dousing the flame: reviewing the mechanisms of inflammatory programming during stress-induced intrauterine growth restriction and the potential for ω-3 polyunsaturated fatty acid intervention

White,

Yates

2023

Front. Physiol.

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Intrauterine growth restriction (IUGR) arises when maternal stressors coincide with peak placental development, leading to placental insufficiency. When the expanding nutrient demands of the growing fetus subsequently exceed the capacity of the stunted placenta, fetal hypoxemia and hypoglycemia result. Poor fetal nutrient status stimulates greater release of inflammatory cytokines and catecholamines, which in turn lead to thrifty growth and metabolic programming that benefits fetal survival but is maladaptive after birth. Specifically, some IUGR fetal tissues develop enriched expression of inflammatory cytokine receptors and other signaling cascade components, which increases inflammatory sensitivity even when circulating inflammatory cytokines are no longer elevated after birth. Recent evidence indicates that greater inflammatory tone contributes to deficits in skeletal muscle growth and metabolism that are characteristic of IUGR offspring. These deficits underlie the metabolic dysfunction that markedly increases risk for metabolic diseases in IUGR-born individuals. The same programming mechanisms yield reduced metabolic efficiency, poor body composition, and inferior carcass quality in IUGR-born livestock. The ω-3 polyunsaturated fatty acids (PUFA) are diet-derived nutraceuticals with anti-inflammatory effects that have been used to improve conditions of chronic systemic inflammation, including intrauterine stress. In this review, we highlight the role of sustained systemic inflammation in the development of IUGR pathologies. We then discuss the potential for ω-3 PUFA supplementation to improve inflammation-mediated growth and metabolic deficits in IUGR offspring, along with potential barriers that must be considered when developing a supplementation strategy.

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“…Various readily available materials such as plasma, red blood cells, and urine can be examined. The integration of lipidome and proteome network analyses is a promising approach to better understand the overall molecular signatures induced by dietary interventions 8 . This may help to monitor well known key mechanisms including adequate glucose utilization, 9,10 composition of cell membranes, 8,11 oxidative stress, lipotoxicity, and proinflammatory signaling 12 as well as to discover new molecular targets for dietary interventions with the goal to promote cell function and maintain cell integrity.…”

mentioning

confidence: 99%

Molecular effects of dietary interventions—A clinical perspective

Nüsken,

Nüsken

2023

Acta Physiologica

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Elevated n-3/n-6 PUFA ratio in early life diet reverses adverse intrauterine kidney programming in female rats

Cited by 4 publications

References 89 publications

The effect of mycophenolate mofetil on podocytes in nephrotoxic serum nephritis

The effect of mycophenolate mofetil on podocytes in nephrotoxic serum nephritis

Dousing the flame: reviewing the mechanisms of inflammatory programming during stress-induced intrauterine growth restriction and the potential for ω-3 polyunsaturated fatty acid intervention

Molecular effects of dietary interventions—A clinical perspective

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