Postnatal endotoxin exposure results in increased insulin sensitivity and altered activity of neuroendocrine axes in adult female rats

Nilsson, Cecilia; Jennische, Eva; Ho, Hoi-Por; Eriksson, Elias; Björntorp, Per; Holmäng, Agneta

doi:10.1530/eje.0.1460251

Cited by 63 publications

(32 citation statements)

References 40 publications

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“…Importantly, exaggerated IL-1␤ responses to LPS in adulthood were specific to the brain, because no group differences were observed in the periphery in any cytokine. Furthermore, we observed no group differences in corticosterone within the serum, a finding consistent with our previous study (Bilbo et al, 2005) but in contrast to several reports that neonatal LPS exposure potentiates hypothalamic-pituitary-adrenal (HPA) activity in adult rodents (Shanks et al, 2000;Hodgson et al, 2001;Nilsson et al, 2002). The phenomenon that HPA activity is altered after neonatal LPS is not unequivocal, however, because some investigators report changes in overall activity (Shanks et al, 2000;Nilsson et al, 2002), some report altered stress-induced activity only (Hodgson et al, 2001;Hodgson and Knott, 2002), and yet others report no change (Granger et al, 1996;Breivik et al, 2002), consistent with our own findings.…”

Section: Alterations In Brain Il-1␤supporting

confidence: 92%

Neonatal Infection-Induced Memory Impairment after Lipopolysaccharide in Adulthood Is Prevented via Caspase-1 Inhibition

Bilbo¹,

Biedenkapp²,

Der-Avakian³

et al. 2005

J. Neurosci.

226

224

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We have reported that neonatal infection leads to memory impairment after an immune challenge in adulthood. Here we explored whether events occurring as a result of early infection alter the response to a subsequent immune challenge in adult rats, which may then impair memory. In experiment 1, peripheral infection with Escherichia coli on postnatal day 4 increased cytokines and corticosterone in the periphery, and cytokine and microglial cell marker gene expression in the hippocampus of neonate pups. Next, rats treated neonatally with E. coli or PBS were injected in adulthood with lipopolysaccharide (LPS) or saline and killed 1-24 h later. Microglial cell marker mRNA was elevated in hippocampus in saline controls infected as neonates. Furthermore, LPS induced a greater increase in glial cell marker mRNA in hippocampus of neonatally infected rats, and this increase remained elevated at 24 h versus controls. After LPS, neonatally infected rats exhibited faster increases in interleukin-1␤ (IL-1␤) within the hippocampus and cortex and a prolonged response within the cortex. There were no group differences in peripheral cytokines or corticosterone. In experiment 2, rats treated neonatally with E. coli or PBS received as adults either saline or a centrally administered caspase-1 inhibitor, which specifically prevents the synthesis of IL-1␤, 1 h before a learning event and subsequent LPS challenge. Caspase-1 inhibition completely prevented LPS-induced memory impairment in neonatally infected rats. These data implicate IL-1␤ in the set of immune/inflammatory events that occur in the brain as a result of neonatal infection, which likely contribute to cognitive alterations in adulthood.

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Section: Alterations In Brain Il-1␤supporting

confidence: 92%

Neonatal Infection-Induced Memory Impairment after Lipopolysaccharide in Adulthood Is Prevented via Caspase-1 Inhibition

Bilbo¹,

Biedenkapp²,

Der-Avakian³

et al. 2005

J. Neurosci.

226

224

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“…Consistent with our study, van der Crabben et al (2009) showed that early endotoxemia increases peripheral and hepatic insulin sensitivity in healthy humans. Furthermore, studies by Nilsson et al (2002) also indicate that postnatal endotoxin exposure results in increased insulin sensitivity and altered activity of neuroendocrine axes in adult female rats. Since significant reduction in resistin expression was observed after LPS treatment, we proposed that low dose of LPS may increase the insulin sensitivity by decreasing the expression of resistin.…”

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide inhibits the expression of resistin in adipocytes

Xiang¹,

Jiang³

et al. 2013

Journal of Molecular Endocrinology

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Resistin is an adipocytokine leading to insulin resistance. Endotoxin/lipopolysaccharide (LPS) has been reported to decrease the expression of resistin mRNA and protein in both lean and db/db obese mice, although the underlying mechanism remains unclear. Several models such as ex vivo culture of adipose tissues, primary rat adipocytes and 3T3-L1 adipocytes were used to further characterize the effect of LPS on the expression of resistin. LPS attenuated both the resistin mRNA and protein in a time-and dose-dependent manner. In the presence of actinomycin D, LPS failed to reduce the half-life of resistin mRNA, suggesting a transcriptional mechanism. The lipid A fraction is crucial for the inhibition of resistin expression induced by LPS. Pharmacological intervention of c-Jun N-terminal kinase (JNK) reversed the inhibitory effect of LPS. LPS down-regulated CCAAT/enhancer-binding protein a (C/EBP-a; CEBPA) and peroxisome proliferator-activated receptor g (PPAR-g; PPARG), while activation of C/EBP-a or PPAR-g by either over-expressing these transcriptional factors or by rosiglitazone, an agonist of PPAR-g, blocked the inhibitory effect of LPS on resistin. C/EBP homologous protein (CHOP-10; DDIT3) was up-regulated by LPS, while a CHOP-10 antisense oligonucleotide reversed the decrement of resistin protein induced by LPS. Taken together, these results suggest that LPS inhibits resistin expression through a unique signaling pathway involving toll-like receptor 4, JNK, CHOP-10 and C/EBP-a/PPAR-g.

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“…Other groups have shown that maternal exposure to multiple injections of endotoxin or some cytokines can lead to increases in body weight, adiposity, and circulating leptin levels in the offspring (15,40,63). In contrast, multiple endotoxin administration during the very early postnatal period (at P3 and P5) has been reported to result in a very slight reduction (62) or no change (39,61) in total body weight. We have now extended this neonatal period to time points that are very sensitive to other programming aspects and still find no effect on weight.…”

Section: Discussionmentioning

confidence: 99%

“…After the fasting experiment, at ϳ19 wk after birth, the rats were euthanized with an overdose of pentobarbital sodium (80 -100 mg/kg ip) and dissected for assessment of brain, adrenal, retroperitoneal fat (left and right), and right tibialis anterior muscle weights. The tibialis anterior was chosen as a representative skeletal muscle as it has previously been shown to be altered by postnatal endotoxin given at P3 and P5 (39). The retroperitoneal fat was chosen as it is a reliably and easily dissected representative fat pad.…”

Section: Methodsmentioning

confidence: 99%

Neonatal immune challenge does not affect body weight regulation in rats

Spencer¹,

Mouihate²,

Galic³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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The perinatal environment plays a crucial role in programming many aspects of adult physiology. Myriad stressors during pregnancy, from maternal immune challenge to nutritional deficiency, can alter longterm body weight set points of the offspring. In light of the increasing concern over body weight issues, such as obesity and anorexia, in modern societies and accumulating evidence that developmental stressors have long-lasting effects on other aspects of physiology (e.g., fever, pain), we explored the role of immune system activation during neonatal development and its impact on body weight regulation in adulthood. Here we present a thorough evaluation of the effects of immune system activation (LPS, 100 g/kg ip) at postnatal days 3, 7, or 14 on long-term body weight, adiposity, and body weight regulation after a further LPS injection (50 g/kg ip) or fasting and basal and LPS-induced circulating levels of the appetite-regulating proinflammatory cytokine leptin. We show that neonatal exposure to LPS at various times during the neonatal period has no long-term effects on growth, body weight, or adiposity. We also observed no effects on body weight regulation in response to a short fasting period or a further exposure to LPS. Despite reductions in circulating leptin levels in response to LPS during the neonatal period, no long-term effects on leptin were seen. These results convincingly demonstrate that adult body weight and weight regulation are, unlike many other aspects of adult physiology, resistant to programming by a febrile-dose neonatal immune challenge.gender; leptin; lipopolysaccharide; obesity THE PERINATAL ENVIRONMENT is known to play a crucial role in programming body weight. In humans, low birth weight and malnutrition during gestation have been linked with abdominal obesity in adulthood (31,45,46). Similarly, a variety of behavioral, physiological (including dietary manipulations), and immune stressors given to pregnant experimental animals have been reported to alter the body weight of adult offspring (4,15,27,36,40,63). It appears, however, that the timing of perinatal stress is critical in programming many aspects of adult physiology (35) and relatively little is known regarding the influence of postnatal stress on adult body weight regulation.The long-term physiological consequences of a neonatal immune challenge with LPS have been extensively described by our laboratory and others. For example, we have shown attenuated febrile and associated host defense responses in adulthood to an immune challenge of the same type as that experienced at postnatal day (P) 14 (9,17,18). Changes have also been demonstrated in memory processing (7), hypothalamic-pituitary-adrenal axis activation (51, 52), and susceptibility to pathological insults in adulthood (10, 55, 56). However, the long-term effects of a neonatal immune challenge on body weight regulation are less clear, and given the concern over the current obesity epidemic in modern society [e.g., (29)], demand further investigation. For instance, Walker ...

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Postnatal endotoxin exposure results in increased insulin sensitivity and altered activity of neuroendocrine axes in adult female rats

Cited by 63 publications

References 40 publications

Neonatal Infection-Induced Memory Impairment after Lipopolysaccharide in Adulthood Is Prevented via Caspase-1 Inhibition

Neonatal Infection-Induced Memory Impairment after Lipopolysaccharide in Adulthood Is Prevented via Caspase-1 Inhibition

Lipopolysaccharide inhibits the expression of resistin in adipocytes

Neonatal immune challenge does not affect body weight regulation in rats

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