12 research outputs found
Prenatal stress-mediated fetal programming of obesity in diet-induced obese and dietary resistant rats
No full textGenotype, diet and environment or life style factors are known to be associated with the development of obesity and metabolic syndrome in adults. However, recent evidence suggests that prenatal factors could contribute to obesity as well. One of the prenatal factors implicated in the development of metabolic syndrome in the offspring is stress, which is known to increase circulating glucocorticoids during pregnancy. Prolonged exposure of the developing fetus to excess glucocorticoid levels results in long lasting neuroendocrine changes which predispose the offspring to obesity and other cardiovascular disorders. Considering the fact that 30% of today's maternal population is obese, it is also important to address the impact of prenatal stress in the background of maternal obesity. Hence, we used diet-induced obese (DIO) and dietary resistant (DR) rat model to explore the mechanisms underlying prenatal stress mediated fetal programming of obesity in DIO and DR rats. Prenatal stress was associated with catch up growth and hyperinsulinemia in the DIO offspring. Although, prenatal stress reduced birth weight in the DR offspring, it did not result in any other adverse metabolic outcomes. Next, we investigated the role of stress axis hyperactivation in prenatal stress-induced metabolic programming in the DIO offspring. In the DIO rats, prenatal stress resulted in hyperactivation of stress axis marked by increased norepinephrine (NE) levels in the paraventricular nucleus in the  hypothalamus and increased corticotrophin releasing hormone levels in the median eminence. However, the serum corticosterone (CORT) levels were not altered in the prenatally stressed DIO and DR offspring. Despite, no change in circulating CORT levels, glucocorticoids might play a role in metabolic syndrome through increasing 11β-hydroxysteroid dehydrogenase enzyme (11βHSD1) in the target tissues. 11βHSD1 is highly expressed in metabolically active tissues like liver and adipose tissue and is involved in the intracellular generation of CORT by converting inactive 11-dehydroCORT to active CORT. Hence, we investigated the role of 11βHSD1 in the liver and adipose tissue in prenatal stress mediated metabolic programming. Prenatal stress significantly increased 11βHSD1 mRNA and protein expression in the visceral adipose tissue accompanied with hypertrophied adipocytes in the DIO offspring. There were no differences in 11βHSD1 expression in the liver suggesting prenatal stress results in tissue-specific programming of 11βHSD1 expression. Taken together, the results suggest that prenatal stress produces differential metabolic effects in DIO and DR rats. Further, 11βHSD1 could mediate the metabolic effects observed in the prenatally stressed offspring and thus may be a potential mechanism for fetal origins of obesity.Thesis (Ph. D.)--Michigan State University. Pharmacology and Toxicology-Environmental Toxicology, 2012Includes bibliographical references (pages 159-178
Lipopolysaccharide stimulates norepinephrine efflux from the rat hypothalamus in vitro: blockade by soluble IL-1 receptor
No full textSpecificity of interleukin–1β-induced changes in monoamine concentrations in hypothalamic nuclei: blockade by interleukin-1 receptor antagonist
No full textEffects of bacterial lipopolysaccharide on central monoamines and fever in the rat: involvement of the vagus
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Lipopolysaccharide-induced changes in monoamines in specific areas of the brain: blockade by interleukin-1 receptor antagonist1Preliminary results were presented at the Experimental Biology meeting, Atlanta, GA, USA, 1995.1
No full textDifferential effects of systemic interleukin-1β on gene expression in brainstem noradrenergic nuclei
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Activation of the Stress Axis and Neurochemical Alterations in Specific Brain Areas by Concentrated Ambient Particle Exposure with Concomitant Allergic Airway Disease
No full textResponsiveness of hypothalamo-pituitary-adrenal axis to leptin is impaired in diet-induced obese rats
No full textThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Background/objectives:
Diet-induced obese (DIO) rats have altered stress (HPA) axis activity compared to diet-resistant (DR) rats when chronically exposed to a high-fat (HF) diet. Since stress axis is tightly regulated by leptin, an adipocyte-secreted hormone that is important for controlling body weight, we hypothesized that leptin action is impaired in DIO rats leading to alterations in HPA axis activity.
Subjects/methods:
We intraperitoneally injected selectively bred DIO and DR rats with either saline or recombinant rat leptin. HPA axis activity was assessed by measuring norepinephrine (NE) in the paraventricular nucleus (PVN), corticotropin-releasing hormone (CRH) in the median eminence, and serum corticosterone (CORT). To test if HF exposure duration and the corresponding increase in leptin differentially affects HPA axis activity, we placed animals on a chow or HF diet for 1 or 6 weeks.
Results:
Leptin injection significantly increased serum leptin levels in both DIO and DR animals. It also reduced PVN NE in both groups, indicating that noradrenergic neurons in both groups remain responsive to leptin. HF diet duration-dependently increased serum leptin only in DIO animals whereas PVN NE increased in both groups. While DR rats responded to HF diet by increasing CRH and CORT at both time-points, responses in DIO rats varied, suggesting that they have altered HPA axis activity that may be dependent on HF-induced leptin levels and/or signaling. To understand the underlying mechanisms, we measured pSTAT-3, a marker of leptin signaling, in brainstem noradrenergic neurons and found reduced pSTAT-3 in A1 region of HF-fed DIO rats. We also found higher serum free fatty acids (FFAs) and a pro-inflammatory cytokine, IL-1β.
Conclusions:
Collectively, these findings reveal that DIO rats have inherent neuroendocrine impairment in NE-HPA axis circuitry that worsens with the extent of HF diet exposure, possibly due to brainstem leptin resistance and/or elevated circulating FFAs and IL-1β
