LPS induces rapid increase in GDF15 levels in mice, rats and humans but is not required for anorexia in mice

2021 ◽  
Author(s):  
Anita Patel ◽  
Henriette Frikke-Schmidt ◽  
Olivier Bezy ◽  
Paul V Sabatini ◽  
Nikolaj Rittig ◽  
...  
Keyword(s):  
Food Intake ◽  
Cancer Cachexia ◽  
Systemic Infection ◽  
Body Weight Loss ◽  
Housing Temperature ◽  
Low Levels ◽  
Physiologic Responses ◽  
Lps Treatment ◽  
Tgfβ Superfamily

Growth differentiation factor 15 (GDF15), a TGFβ superfamily cytokine, acts through its receptor, GDNF-family receptor α-like (GFRAL), to suppress food intake and promote nausea. GDF15 is broadly expressed at low levels but increases in states of disease such as cancer, cachexia, and sepsis. Whether GDF15 is necessary for inducing sepsis associated anorexia and body weight loss is currently unclear. To test this we used a model of moderate systemic infection in GDF15KO and GFRALKO mice with lipopolysaccharide (LPS) treatment to define the role of GDF15 signaling in infection-mediated physiologic responses. Since physiologic responses to LPS depend on housing temperature, we tested the effects of subthermoneutral and thermoneutral conditions on eliciting anorexia and inducing GDF15. Our data demonstrate a conserved LPS-mediated increase in circulating GDF15 levels in mouse, rat and human. However, we did not detect differences in LPS induced anorexia between WT and GDF15KO or GFRALKO mice. Further, there were no differences in anorexia or circulating GDF15 levels at either thermoneutral or subthermoneutral housing conditions in LPS treated mice. These data demonstrate that GDF15 is not necessary to drive food intake suppression in response to moderate doses of LPS.

Role of Antibody to Native Type III Polysaccharide of Group B Streptococcus in Infant Infection

PEDIATRICS ◽  
1981 ◽  
Vol 68 (4) ◽  
pp. 544-549 ◽  
Author(s):  
Carol J. Baker ◽  
Morven S. Edwards ◽  
Dennis L. Kasper
Keyword(s):  
Group B Streptococcus ◽  
Systemic Infection ◽  
Group B Streptococci ◽  
Symptomatic Infection ◽  
Type Iii ◽  
Vaginal Colonization ◽  
Low Levels ◽  
Group B ◽  
Antibody Levels

The role of maternally acquired antibody to native type III polysacchande of group B Streptococcus as a determinant of susceptibility for infant systemic infection was investigated. Sera from 11 1 acutely ill infants with type III group B streptococcal bacteremia and/or meningitis and their mothers, and cord sera from 45 healthy neonates and their mothers who had type III group B streptococcal vaginal colonization at delivery were studied. Sera from each of 111 acutely ill infants contained very low levels ofantibody (sjlt 1.7 µg/ml, median 0.4 µg/ml), and a significant correlation with maternal levels was tested for early onset infection (median 0.6 µg/ml; r = .76; P sjlt .01). Women whose infants remained well had antibody levels sjgt 2 µg/ml in their sera (73%) more often than those whose infants developed symptomatic infection (17%) (P sjlt .001), and the median level in their sera (12.6 µg/ml) was considerably higher. Study of sera obtained during convalescence from 86 surviving infants indicated a poor antibody response to infection. In contrast, high levels of antibody were detected in sera from each of five convalescent women with postpartum bacteremia. These data extend earlier observations suggesting the correlation between low levels of type-specific antibody in serum and risk for systemic infection with type III strains of group B streptococci.

scholarly journals Protein tyrosine phosphatase-1B contributes to LPS-induced leptin resistance in male rats

2015 ◽  
Vol 308 (1) ◽  
pp. E40-E50 ◽  
Author(s):  
Beatriz de Carvalho Borges ◽  
Rodrigo C. Rorato ◽  
Ernane Torres Uchoa ◽  
Paula B. Marangon ◽  
Carol F. Elias ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Leptin Receptor ◽  
Tyrosine Phosphatase ◽  
Body Weight Loss ◽  
Male Rats ◽  
Leptin Resistance ◽  
Reduce Food Intake ◽  
Low Grade ◽  
Lps Treatment

Leptin resistance is induced by the feedback inhibitors tyrosine phosphatase-1B (PTP1B) and decreased Src homology 2 domain-containing tyrosine phosphatase-2 (SHP-2) signaling. To investigate the participation of PTP1B and SHP-2 in LPS-induced leptin resistance, we injected repeated (6-LPS) intraperitoneal LPS doses (100 μg/kg ip) for comparison with a single (1-LPS) treatment and evaluated the expression of SHP-2, PTP1B, p-ERK1/2, and p-STAT3 in the hypothalamus of male Wistar rats. The single LPS treatment increased the expression of p-STAT3 and PTP1B but not SHP-2. The repeated LPS treatment reduced SHP-2, increased PTP1B, and did not change p-STAT3. We observed that the PTP1B expression induced by the endotoxin was highly colocalized with leptin receptor cells in the hypothalamus of LepRb-IRES-Cre-tdTomato reporter mice. The single, but not the repeated, LPS treatment decreased the food intake and body weight. Leptin had no stimulatory effect on the hypophagia, body weight loss, or pSTAT3 expression in 6-LPS rats, indicating leptin unresponsiveness. Notably, the PTP1B inhibitor (3.0 nmol/rat in 5 μl icv) restored the LPS-induced hypophagia in 6-LPS rats and restored the ability of leptin to reduce food intake and body weight as well as to phosphorylate STAT3 in the arcuate, paraventricular, and ventromedial nuclei of the hypothalamus. The present data suggest that an increased PTP1B expression in the hypothalamus underlies the development of leptin resistance during repeated exposure to LPS. Our findings contribute to understanding the mechanisms involved in leptin resistance during low-grade inflammation as seen in obesity.

scholarly journals Coix seed oil ameliorates cancer cachexia by counteracting muscle loss and fat lipolysis

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Huiquan Liu ◽  
Lu Li ◽  
Jun Zou ◽  
Ting Zhou ◽  
Bangyan Wang ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Food Intake ◽  
Cancer Cachexia ◽  
Seed Oil ◽  
Body Weight Loss ◽  
Tissue Loss ◽  
Epididymal Adipose Tissue ◽  
Tnf Α ◽  
Coix Seed

Abstract Background Cancer cachexia is a cancer-induced multifactorial debilitating syndrome directly accounting for 20% of cancer deaths without effective therapeutic approaches. It is extremely urgent to explore effective anti-cachexia drugs to ameliorate muscle and fat loss in cachexia patients. Methods Lewis lung carcinoma bearing C57BL/6 mice were applied as the animal model to examine the therapeutic effect of Coix seed oil (CSO) on cancer cachexia. The food intake and body weight change were monitored every 3 days throughout the experiment. The IL-6 and TNF-α levels in serum were detected by ELISA assay. Several key proteins involved in muscle wasting and fat lipolysis were tested by Western blot to identify the potential mechanism of CSO. Results Administration of CSO through gavage significantly prevented body weight loss and ameliorated systemic inflammation without affecting food intake and tumor size. The weight and histological morphology of gastrocnemius muscle and epididymal adipose tissue in CSO-treated mice were also improved. In mechanism, we found that CSO decreased the expression of MuRF1 and the ratio of phospho-p65 (Ser536) to p65 in muscle tissue. Meanwhile, cancer-induced activation of HSL and AMPK was also inhibited by CSO administration. Conclusion Coix seed oil exerts an anti-cachexia pharmaceutical effect by counteracting muscle and adipose tissue loss most likely through regulating NF-κB-MuRF1 and AMPK-HSL pathway.

scholarly journals Altered acylated ghrelin response to food intake in congenital generalized lipodystrophy

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0244667
Author(s):  
Camilla O. D. Araújo ◽  
Renan M. Montenegro ◽  
Amanda P. Pedroso ◽  
Virgínia O. Fernandes ◽  
Ana Paula D. R. Montenegro ◽  
...  
Keyword(s):  
Food Intake ◽  
Analogue Scale ◽  
Caloric Intake ◽  
Acylated Ghrelin ◽  
Congenital Generalized Lipodystrophy ◽  
Meal Intake ◽  
Obese Subjects ◽  
Ad Libitum ◽  
Low Levels

Background Patients with congenital generalized lipodystrophy (CGL) have very low levels of leptin and are described as having a voracious appetite. However, a direct comparison between CGL and eutrophic individuals is lacking, regarding both appetite parameters and acylated ghrelin, the hormone form that is active in acute food intake stimulation. The objective of the present study was to address whether and in what extent the subjective appetite parameters and acylated ghrelin response to a meal are affected in CGL individuals, in comparison to eutrophic individuals. Additionally, an obese group was included in the study, to allow the comparison between a leptin-resistant and a leptin-deficient condition on these aspects. Methods Eutrophic controls (EUT, n = 10), obese subjects (OB, n = 10) and CGL (n = 11) were fasted overnight and then received an ad libitum meal. Blood was collected and the visual analogue scale was applied before and 90 minutes after the meal. An additional blood sample was collected at 60 minutes for ghrelin determination. Results The CGL patients showed low fasting levels of leptin and adiponectin, dyslipidemia, and insulin resistance. The caloric intake was similar among the 3 groups. However, both CGL (p = 0.02) and OB (p = 0.04) had shorter satiation times than EUT. The CGL patients also had lower satiety time (p = 0.01) and their sensation of hunger was less attenuated by the meal (p = 0.03). Fasting acylated ghrelin levels were lower in CGL than in EUT (p = 0.003). After the meal, the levels tended to decrease in EUT but not in CGL and OB individuals. Conclusion The data indicate that, although not hyperphagic, the CGL patients present appetite disturbances in relation to eutrophic individuals. Their low fasting levels of acylated ghrelin and the absence of the physiological drop after meal intake suggest a role of these disturbances in hunger attenuation and satiety but not in acute satiation.

scholarly journals Regulation of Food Intake and Gonadotropin-Releasing Hormone/Luteinizing Hormone during Lactation: Role of Insulin and Leptin

Endocrinology ◽  
2009 ◽  
Vol 150 (9) ◽  
pp. 4231-4240 ◽  
Author(s):  
Jing Xu ◽  
Melissa A. Kirigiti ◽  
Kevin L. Grove ◽  
M. Susan Smith
Keyword(s):  
Energy Balance ◽  
Food Intake ◽  
Negative Energy ◽  
Serum Glucose ◽  
Negative Energy Balance ◽  
Serum Lh ◽  
Low Levels ◽  
Agouti Related Protein ◽  
Insulin Replacement

Abstract Negative energy balance during lactation is reflected by low levels of insulin and leptin and is associated with chronic hyperphagia and suppressed GnRH/LH activity. We studied whether restoration of insulin and/or leptin to physiological levels would reverse the lactation-associated hyperphagia, changes in hypothalamic neuropeptide expression [increased neuropeptide Y (NPY) and agouti-related protein (AGRP) and decreased proopiomelanocortin (POMC), kisspeptin (Kiss1), and neurokinin B (NKB)] and suppression of LH. Ovariectomized lactating rats (eight pups) were treated for 48 h with sc minipumps containing saline, human insulin, or rat leptin. The arcuate nucleus (ARH) was analyzed for NPY, AGRP, POMC, Kiss1, and NKB mRNA expression; the dorsal medial hypothalamus (DMH) was analyzed for NPY mRNA. Insulin replacement reversed the increase in ARH NPY/AGRP mRNAs, partially recovered POMC, but had no effect on recovering Kiss1/NKB. Leptin replacement only affected POMC, which was fully recovered. Insulin/leptin dual replacement had similar effects as insulin replacement alone but with a slight increase in Kiss1/NKB. The lactation-induced increase in DMH NPY was unchanged after treatments. Restoration of insulin and/or leptin had no effect on food intake, body weight, serum glucose or serum LH. These results suggest that the negative energy balance of lactation is not required for the hyperphagic drive, although it is involved in the orexigenic changes in the ARH. The chronic hyperphagia of lactation is most likely sustained by the induction of NPY in the DMH. The negative energy balance also does not appear to be a necessary prerequisite for the suppression of GnRH/LH activity.

scholarly journals Unconjugated Bilirubin Attenuates DSS-Induced Colitis Potentially via Enhancement of Bilirubin Reabsorption

2021 ◽  
Vol 12 ◽  
Author(s):  
Chong Zhao ◽  
Hongli Huang ◽  
Qiuhua Pan ◽  
Wenqi Huang ◽  
Wu Peng ◽  
...  
Keyword(s):  
Antioxidant Capacity ◽  
Serum Bilirubin ◽  
Body Weight Loss ◽  
Inflammatory Cells ◽  
Unconjugated Bilirubin ◽  
Retrospective Case ◽  
Total Antioxidant ◽  
Low Levels ◽  
Pre Treatment

Studies increasingly show that ulcerative colitis (UC) is a consequence of an imbalance between oxidative stress and antioxidant capacity. Bilirubin exerts an anti-inflammatory effect by scavenging reactive oxygen species (ROS), although the exact mechanism is not completely understood. The aim of this study was to determine the role of serum bilirubin in UC using patient data and a mouse model of dextran sodium sulfate (DSS)-induced colitis. We found that low levels of serum bilirubin correlated to a higher risk of UC in a retrospective case-control population. Pre-treatment with exogenous unconjugated bilirubin (UCB) significantly enhanced colonic bilirubin absorption in mice, and attenuated the DSS-induced body weight loss, colon shortening and histopathological damage. Mechanistically, bilirubin prevented the infiltration of inflammatory cells, and decreased the levels of myeloperoxidase and pro-inflammatory cytokines in the serum and colon. Moreover, bilirubin inhibited ROS and malondialdehyde production, scavenged superoxide anions (O2·−) from the colon and enhanced the total antioxidant capacity. In conclusion, exogenous UCB attenuated DSS-induced colitis by directly scavenging O2·− and enhancing bilirubin reabsorption in the colon via enterohepatic cycling.

Social Motives Predict Loneliness During a Developmental Transition

2017 ◽  
Vol 76 (4) ◽  
pp. 145-153 ◽  
Author(s):  
Jana Nikitin ◽  
Alexandra M. Freund
Keyword(s):  
Social Relationships ◽  
Well Being ◽  
Social Avoidance ◽  
Social Approach ◽  
Social Motives ◽  
Developmental Transitions ◽  
Avoidance Motivation ◽  
Negative Effect ◽  
Low Levels

Abstract. Establishing new social relationships is important for mastering developmental transitions in young adulthood. In a 2-year longitudinal study with four measurement occasions (T1: n = 245, T2: n = 96, T3: n = 103, T4: n = 85), we investigated the role of social motives in college students’ mastery of the transition of moving out of the parental home, using loneliness as an indicator of poor adjustment to the transition. Students with strong social approach motivation reported stable and low levels of loneliness. In contrast, students with strong social avoidance motivation reported high levels of loneliness. However, this effect dissipated relatively quickly as most of the young adults adapted to the transition over a period of several weeks. The present study also provides evidence for an interaction between social approach and social avoidance motives: Social approach motives buffered the negative effect on social well-being of social avoidance motives. These results illustrate the importance of social approach and social avoidance motives and their interplay during developmental transitions.

Social and Temporal Comparisons as Moderators of Psychological Resources Associations With Wellbeing

2016 ◽  
Vol 37 (2) ◽  
pp. 96-104 ◽  
Author(s):  
Hasida Ben-Zur
Keyword(s):  
Life Satisfaction ◽  
Positive Affect ◽  
Subjective Wellbeing ◽  
Social Comparisons ◽  
Self Esteem ◽  
Psychological Resources ◽  
Low Levels ◽  
Age Range ◽  
General Wellbeing

Abstract. The current study investigated the associations of psychological resources, social comparisons, and temporal comparisons with general wellbeing. The sample included 142 community participants (47.9% men; age range 23–83 years), who compared themselves with others, and with their younger selves, on eight dimensions (e.g., physical health, resilience). They also completed questionnaires assessing psychological resources of mastery and self-esteem, and three components of subjective wellbeing: life satisfaction and negative and positive affect. The main results showed that high levels of psychological resources contributed to wellbeing, with self-enhancing social and temporal comparisons moderating the effects of resources on certain wellbeing components. Specifically, under low levels of mastery or self-esteem self-enhancing social or temporal comparisons were related to either higher life satisfaction or positive affect. The results highlight the role of resources and comparisons in promoting people’s wellbeing, and suggest that self-enhancing comparisons function as cognitive coping mechanisms when psychological resources are low.

Ups and downs on the roller coaster of task conflict: the role of group cognitive complexity, collective emotional intelligence and team creativity

2020 ◽  
Vol 18 (1) ◽  
pp. 23-37
Author(s):  
Andreea Gheorghe ◽  
Oana Fodor ◽  
Anișoara Pavelea
Keyword(s):  
Emotional Intelligence ◽  
Cognitive Complexity ◽  
Empirical Support ◽  
Task Conflict ◽  
Team Creativity ◽  
Mediating Role ◽  
Low Levels ◽  
Explanatory Mechanism ◽  
The Relationship

This study explores the association between task conflict and team creativity and the role of group cognitive complexity (GCC) as a potential explanatory mechanism in a sample of 159 students organized in 49 groups. Moreover, we analyzed the moderating effect of collective emotional intelligence (CEI)in the relationship between task conflict and GCC.As hypothesized, we found that task conflict has a nonlinear relationship with GCC, but contrary to our expectations, it follows a U-shaped association, not an inversed U-shape. In addition,the moderating role of CEI was significant only at low levels. Contrary to our expectation, the mediating role of GCC did not receive empirical support. Theoretical and practical contributions are discussed.

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