scholarly journals Priming of Hypothalamic Ghrelin Signaling and Microglia Activation Exacerbate Feeding in Rats’ Offspring Following Maternal Overnutrition

Nutrients ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1241 ◽  
Author(s):  
Roger Maldonado-Ruiz ◽  
Marcela Cárdenas-Tueme ◽  
Larisa Montalvo-Martínez ◽  
Roman Vidaltamayo ◽  
Lourdes Garza-Ocañas ◽  
...  
Keyword(s):  
Food Intake ◽  
Palmitic Acid ◽  
Cell Activation ◽  
Programming Model ◽  
Microglia Activation ◽  
Tnf Alpha ◽  
Primary Microglia ◽  
Female Wistar Rats ◽  
C6 Ceramide ◽  
Maternal Overnutrition

Maternal overnutrition during pregnancy leads to metabolic alterations, including obesity, hyperphagia, and inflammation in the offspring. Nutritional priming of central inflammation and its role in ghrelin sensitivity during fed and fasted states have not been analyzed. The current study aims to identify the effect of maternal programming on microglia activation and ghrelin-induced activation of hypothalamic neurons leading to food intake response. We employed a nutritional programming model exposing female Wistar rats to a cafeteria diet (CAF) from pre-pregnancy to weaning. Food intake in male offspring was determined daily after fasting and subcutaneous injection of ghrelin. Hypothalamic ghrelin sensitivity and microglia activation was evaluated using immunodetection for Iba-1 and c-Fos markers, and Western blot for TBK1 signaling. Release of TNF-alpha, IL-6, and IL-1β after stimulation with palmitic, oleic, linoleic acid, or C6 ceramide in primary microglia culture were quantified using ELISA. We found that programmed offspring by CAF diet exhibits overfeeding after fasting and peripheral ghrelin administration, which correlates with an increase in the hypothalamic Iba-1 microglia marker and c-Fos cell activation. Additionally, in contrast to oleic, linoleic, or C6 ceramide stimulation in primary microglia culture, stimulation with palmitic acid for 24 h promotes TNF-alpha, IL-6, and IL-1β release and TBK1 activation. Notably, intracerebroventricular (i.c.v.) palmitic acid or LPS inoculation for five days promotes daily increase in food intake and food consumption after ghrelin administration. Finally, we found that i.c.v. palmitic acid substantially activates hypothalamic Iba-1 microglia marker and c-Fos. Together, our results suggest that maternal nutritional programing primes ghrelin sensitivity and microglia activation, which potentially might mirror hypothalamic administration of the saturated palmitic acid.

scholarly journals The mechanism of increased intestinal palmitic acid absorption and its impact on hepatic stellate cell activation in nonalcoholic steatohepatitis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Masakazu Hanayama ◽  
Yasunori Yamamoto ◽  
Hiroki Utsunomiya ◽  
Osamu Yoshida ◽  
Shuang Liu ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Portal Vein ◽  
Palmitic Acid ◽  
Intestinal Absorption ◽  
Nonalcoholic Steatohepatitis ◽  
Cell Activation ◽  
Stellate Cell ◽  
Mrna Levels ◽  
Nonalcoholic Fatty Liver ◽  
Chylomicron Formation

AbstractDietary palmitic acid (PA) promotes liver fibrosis in patients with nonalcoholic steatohepatitis (NASH). Herein, we clarified the intestinal absorption kinetics of dietary PA and effect of trans-portal PA on the activation of hepatic stellate cells (HSCs) involved in liver fibrosis in NASH. Blood PA levels after meals were significantly increased in patients with NASH compared to those in the control. Expression of genes associated with fat absorption and chylomicron formation, such as CD36 and MTP, was significantly increased in the intestine of NASH model rats compared with that in the controls. Plasma levels of glucagon-like peptide-2, involved in the upregulation of CD36 expression, were elevated in NASH rats compared with those in the controls. Furthermore, portal PA levels after meals in NASH rats were significantly higher than those in control and nonalcoholic fatty liver rats. Moreover, PA injection into the portal vein to the liver in control rats increased the mRNA levels associated with the activation of HSCs. Increased intestinal absorption of diet-derived PA was observed in NASH. Thus, the rapid increase in PA levels via the portal vein to the liver may activate HSCs and affect the development of liver fibrosis in NASH.

scholarly journals TNF-alpha-induced microglia activation requires miR-342: impact on NF-kB signaling and neurotoxicity

2020 ◽  
Vol 11 (6) ◽  
Author(s):  
João Paulo Brás ◽  
Joana Bravo ◽  
Jaime Freitas ◽  
Mário Adolfo Barbosa ◽  
Susana Gomes Santos ◽  
...  
Keyword(s):  
Microglia Activation ◽  
Tnf Alpha

scholarly journals BLUEBERRY INHIBITS LPS-INDUCED MURINE MICROGLIA CELL ACTIVATION AND CELL DEATH

2013 ◽  
Vol 10 (1-2) ◽  
pp. 87-92 ◽  
Author(s):  
M. A. Miah ◽  
S. S. Choi ◽  
S. H. Lee
Keyword(s):  
Cell Activation ◽  
Stress Conditions ◽  
Microglia Activation ◽  
Dependent Manner ◽  
Microglia Cell ◽  
Treatment Groups ◽  
Murine Microglia ◽  
Mrna And Protein Expression ◽  
Stress Related Genes

Microglia activation plays a pivotal role in varying stress conditions including oxidation, inflammation and certain neurodegenerative diseases. iNOS and PrxI are known to up regulate in LPS-activated microglia in vitro. Natural fruits including various berries containing both antioxidants and anti-inflammatory polyphenols may attenuate such stress conditions. We investigated the effects of blueberry extracts (BBE) on the LPS-activated stress related genes up regulation using BV-2 microglia cells in vitro. BV-2 cells were cultured in DMEM with 10% FBS, were pre-incubated with 50 µg/ml BBE for 0, 1 h and 12 h, and treated with 1µg/ml LPS for 24 h . The levels of mRNA and protein expression showed significant differences in iNOS and PrxI among the treatment groups. Hoechst and PI staining showed that BBE protects cells from activation induced death. Intracellular levels of ROS were increased by LPS stimulation over the level in the control cells whereas BBE treatment significantly lowered the LPS stimulated ROS levels at a time dependent manner. High expressions of iNOS and PrxI are indication of microglia activation and treatment with BBE in LPS-activated BV-2 cells cause down regulation of stress-related genes expression and protect the cells from over activation and death. DOI: http://dx.doi.org/10.3329/bjvm.v10i1-2.15651

scholarly journals Effects of Altered Food Intake during Pubertal Development in Male and Female Wistar Rats

2007 ◽  
Vol 100 (1) ◽  
pp. 194-202 ◽  
Author(s):  
Susan C. Laws ◽  
Tammy E. Stoker ◽  
Janet M. Ferrell ◽  
Michelle G. Hotchkiss ◽  
Ralph L. Cooper
Keyword(s):  
Food Intake ◽  
Wistar Rats ◽  
Pubertal Development ◽  
Male And Female ◽  
Female Wistar Rats

scholarly journals The Role of Toll-Like Receptor 4 Mediates Microglial Activation during Remifentanil-Induced Hyperalgesia in Rats

2019 ◽  
Author(s):  
xiangxiang chen ◽  
Xin Wei
Keyword(s):  
Mechanical Allodynia ◽  
Cell Activation ◽  
Thermal Hyperalgesia ◽  
Microglia Activation ◽  
Toll Like Receptor ◽  
Sprague Dawley ◽  
Toll Like Receptor 4 ◽  
Withdrawal Threshold ◽  
Incisional Pain

Abstract Background: Opioids can induce a state of nociceptive sensitization, also known as opioid-induced hyperalgesia. Nevertheless, the exact mechanism is still unclear. The following study investigates the role of Toll-like receptor 4 (TLR4) in the microglia activation during remifentanil—induced hyperalgesia in rats’ model of incisional pain. Methods: Mechanical allodynia induced by remifentanil was established in adult male Sprague–Dawley rats with incisional pain. Paw withdrawal threshold (PWT) and paw withdrawal thermal latency (PWTL) were performed to evaluate mechanical and thermal hyperalgesia. The 32-G catheter intrathecal placement was used to deliver a specific TLR4 antagonist (LPS-RS).Western blot analysis was performed to measure the expression of the TLR4 and Iba-1, while Immunofluorescence staining was used to investigate the cell type and cell activation. Results：Incisionalpain-remifentanil decreased the PWT and PWTL, upregulated the expression of TLR4 and microglia activation in the spinal cord. On the contrary, the intrathecal delivery of LPS-RS at the dose of 25 μg significantly decreased mechanical allodynia and prevented the upregulation of TLR4 induced by incisional pain-remifentanil Conclusion: These findings suggest that TLR4 signaling pathway has an important role in incisional pain-remifentanil hyperalgesia, and that it could serve as the therapeutic target for persistent postsurgical pain

Effect of serum estradiol and leptin levels on thyroid function, food intake and body weight gain in female Wistar rats

Steroids ◽  
2010 ◽  
Vol 75 (10) ◽  
pp. 638-642 ◽  
Author(s):  
Thiago U. Pantaleão ◽  
Felippe Mousovich ◽  
Doris Rosenthal ◽  
Álvaro S. Padrón ◽  
Denise P. Carvalho ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
Thyroid Function ◽  
Wistar Rats ◽  
Body Weight Gain ◽  
Serum Estradiol ◽  
Female Wistar Rats

Effect of TNF-alpha blockade on coagulopathy and endothelial cell activation in xenoperfused porcine kidneys

2015 ◽  
Vol 22 (4) ◽  
pp. 284-294 ◽  
Author(s):  
Wolf Ramackers ◽  
Johannes Klose ◽  
Andreas Tiede ◽  
Sonja Werwitzke ◽  
Dennis Rataj ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Activation ◽  
Tnf Alpha ◽  
Endothelial Cell Activation ◽  
Alpha Blockade

scholarly journals Necroptosis and microglia activation after chronic ischemic brain injury in mice

2017 ◽  
Vol 15 (2) ◽  
pp. 78-84 ◽  
Author(s):  
Shehong Zhang ◽  
Yuyang Wang ◽  
Hongyu Xie ◽  
Qing Yu ◽  
Junfa Wu ◽  
...  
Keyword(s):  
Brain Injury ◽  
Calcium Binding ◽  
Cell Activation ◽  
Inflammatory Responses ◽  
Interferon Γ ◽  
Microglia Activation ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Bilateral Carotid ◽  
The Brain

Microglia, which are the resident macrophages and the first line of defense in the brain, can be activated within hours and migrate toward the injury sites after acute and chronic ischemic brain injury. However, a few studies have reported the interaction between microglia activation and necroptosis signaling following ischemic damage to the brain. In this study, chronic ischemic brain injury was induced by bilateral carotid artery stenosis (BCAS) and mice were sacrificed at 30 days after surgery. Ionized calcium-binding adaptor molecule 1 (IBA1) and glial fibrillary acidic protein (GFAP) immunostaining were performed to determine glial cell activation and inflammatory response. Tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ), and interleukin-1β (IL-1β) proteins from the brains were examined to confirm inflammatory cytokines after BCAS. RIP1 and RIP3 proteins were detected to determine necroptosis signaling by Western blot. The data suggested that inflammatory responses, microglia activation, and necroptosis signaling are features of brain tissue pathology following BCAS-induced chronic ischemic brain injury.

scholarly journals Protection against lethal toxic shock by targeted disruption of the CD28 gene.

1996 ◽  
Vol 183 (6) ◽  
pp. 2675-2680 ◽  
Author(s):  
B Saha ◽  
D M Harlan ◽  
K P Lee ◽  
C H June ◽  
R Abe
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Toxic Shock Syndrome ◽  
Cell Activation ◽  
Dose Effect ◽  
Tnf Alpha ◽  
Toxic Shock ◽  
Costimulatory Signals ◽  
Toxigenic Strains

Toxic shock syndrome (TSS) is a multi system disorder resulting from superantigen-mediated cytokine production. Nearly 90% of the clinical cases of TSS arise due to an exotoxin, toxic shock syndrome toxin-1 (TSST-1), elaborated by toxigenic strains of Staphylococcus aureus. It is clearly established that besides antigen-specific signals a variety of costimulatory signals are required for full T cell activation. However, the nature and potential redundancy of costimulatory signals are incompletely understood, particularly with regards to superantigen-mediated T cell activation in vivo. Here we report that CD28-deficient mice (CD28-/-) are completely resistant to TSST-1-induced lethal TSS while CD28 (+/-) littermate mice were partially resistant to TSST-1. The mechanism for the resistance of the CD28 (-/-) mice was a complete abrogation of TNF-alpha accumulation in the serum and a nearly complete (90%) impairment of IFN-gamma secretion in response to TSST-1 injection. In contrast, the serum level of IL-2 was only moderately influenced by the variation of CD28 expression. CD28 (-/-) mice retained sensitivity to TNF-alpha as demonstrated by equivalent lethality after cytokine injection. These findings establish an essential requirement for CD28 costimulatory signals in TSST-1-induced TSS. The hierarchy of TSST-1 resistance among CD28 wild-type (CD28+/+), CD28 heterozygous (CD28+/-), and CD28-/- mice suggests a gene-dose effect, implying that the levels of T cell surface CD28 expression critically regulate superantigen-mediated costimulation. Finally, as these results demonstrate the primary and non-redundant role of CD28 receptors in the initiation of the in vivo cytokine cascade, they suggest therapeutic approaches for superantigen-mediated immunopathology.

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