Parasite-induced anorexia: leptin, insulin and corticosterone responses to infection with the nematode, Nippostrongylus brasiliensis

Parasitology ◽  
1999 ◽  
Vol 118 (1) ◽  
pp. 117-123 ◽  
Author(s):  
H. C. ROBERTS ◽  
L. J. HARDIE ◽  
L. H. CHAPPELL ◽  
J. G. MERCER
Keyword(s):  
Gene Expression ◽  
Energy Balance ◽  
Neuropeptide Y ◽  
Post Infection ◽  
Plasma Insulin ◽  
Negative Energy ◽  
Nippostrongylus Brasiliensis ◽  
Corticotrophin Releasing Factor ◽  
Ad Libitum ◽  
Plasma Leptin

The nematode parasite, Nippostrongylus brasiliensis, induces a biphasic anorexia in its rat host. The mechanisms, underlying this anorexia and its possible advantages to the host or parasite are unknown. We have investigated the effect of acute (12–24 h) and chronic (2–17 days) infections on plasma concentrations of leptin, insulin and corticosterone, and on hypothalamic expression of neuropeptide Y, galanin and corticotrophin-releasing factor genes. Plasma leptin was elevated in infected rats relative to uninfected ad libitum-fed controls and pair-fed controls in 12 h infections initiated at dark onset and in infections of 2 days' duration. At other times prior to parasite expulsion, plasma leptin in infected and pair-fed rats was lower than that of uninfected ad libitum-fed controls, reflecting the existing state of negative energy balance. Elevated plasma leptin concentrations in infected rats at day 2 post-infection were accompanied by reduced neuropeptide Y gene expression in the hypothalamic arcuate nucleus compared with both ad libitum control and pair-fed animals, and by lowered corticotrophin-releasing factor gene expression in the paraventricular nucleus relative to pair-feds. Twelve hour infections were characterized by a substantial increase in plasma corticosterone that was independent of reduced food intake, and in 12 h infections initiated at dark onset, where plasma leptin was elevated, there was also increased plasma insulin concentration in infected rats. In longer infections, differences between the groups in plasma insulin and corticosterone concentration were only observed at day 4 post-infection. In summary, perturbations to leptin, insulin and corticosterone signals early in infection may have a causative role and might feed back onto hypothalamic gene expression, whereas subsequent changes in these parameters are more likely to be secondary to negative energy balance.

scholarly journals Photoperiod effects on gene expression for hypothalamic appetite-regulating peptides and food intake in the ram

2003 ◽  
Vol 284 (1) ◽  
pp. R101-R115 ◽  
Author(s):  
Iain J. Clarke ◽  
Alexandra Rao ◽  
Yves Chilliard ◽  
Carole Delavaud ◽  
Gerald A. Lincoln
Keyword(s):  
Gene Expression ◽  
Energy Balance ◽  
Food Intake ◽  
Leptin Receptor ◽  
Negative Energy ◽  
Positive Energy ◽  
Mrna Levels ◽  
Expression Of Genes ◽  
Positive Energy Balance ◽  
Plasma Leptin

Relationship between voluntary food intake (VFI) and gene expression for appetite-regulating peptides was examined in the brains of Soay rams under contrasting photoperiods. Two groups ( n = 8) were subjected to alternating block long-day (LD) and short-day photoperiods (SD) over a period of 42 wk to entrain long-term cycles in VFI. Five animals from each group were killed 18 wk into LD or SD, and the brains were collected for in situ hybridization studies. VFI was fourfold higher under LD compared with SD. Body weight, abdominal fat, or plasma leptin levels were similar under LD and SD. LD animals were in positive energy balance and sexually inactive, and SD animals were in negative energy balance and sexually active. Neuropeptide Y (NPY) mRNA levels were higher in the arcuate nucleus (ARC) under LD, and pro-opiomelanocortin expression was lower under LD. Leptin receptor (Ob-Rb) was higher in the ARC under LD. We conclude that photoperiod-induced increase in VFI correlates with expression of NPY, but not with expression of genes for other putative orexigenic peptides. Ob-Rb gene expression is regulated by photoperiod.

scholarly journals Mammary gene expression profiles during an intramammary challenge reveal potential mechanisms linking negative energy balance with impaired immune response

2010 ◽  
Vol 41 (2) ◽  
pp. 161-170 ◽  
Author(s):  
Kasey M. Moyes ◽  
James K. Drackley ◽  
Dawn E. Morin ◽  
Sandra L. Rodriguez-Zas ◽  
Robin E. Everts ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Energy Balance ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Negative Energy ◽  
Negative Energy Balance ◽  
Differentially Expressed ◽  
Positive Energy ◽  
Ad Libitum

Our objective was to compare mammary tissue gene expression profiles during a Streptococcus uberis ( S. uberis) mastitis challenge between lactating cows subjected to dietary-induced negative energy balance (NEB; n = 5) and cows fed ad libitum to maintain positive energy balance (PEB; n = 5) to better understand the mechanisms associated with NEB and risk of mastitis during the transition period. The NEB cows were feed-restricted to 60% of calculated net energy for lactation requirements for 7 days, and cows assigned to PEB were fed the same diet for ad libitum intake. Five days after feed restriction, one rear mammary quarter of each cow was inoculated with 5,000 cfu of S. uberis (O140J). At 20 h postinoculation, S. uberis-infected mammary quarters from all cows were biopsied for RNA extraction. Negative energy balance resulted in 287 differentially expressed genes (DEG; false discovery rate ≤ 0.05), with 86 DEG upregulated and 201 DEG downregulated in NEB vs. PEB. Canonical pathways most affected by NEB were IL-8 signaling (10 genes), glucocorticoid receptor signaling ( 13 ), and NRF2-mediated oxidative stress response ( 10 ). Among the genes differentially expressed by NEB, cell growth and proliferation ( 48 ) and cellular development ( 36 ) were the most enriched functions. Regarding immune response, HLA-A was upregulated due to NEB, whereas the majority of genes involved in immune response were downregulated (e.g., AKT1, IRAK1, MAPK9, and TRAF6). This study provided new avenues for investigation into the mechanisms relating NEB and susceptibility to mastitis in lactating dairy cows.

Leptin secretion and hypothalamic neuropeptide and receptor gene expression in sheep

2002 ◽  
Vol 282 (4) ◽  
pp. R1227-R1235 ◽  
Author(s):  
Annette Sorensen ◽  
Clare L. Adam ◽  
Pat A. Findlay ◽  
Michel Marie ◽  
Louise Thomas ◽  
...  
Keyword(s):  
Gene Expression ◽  
Receptor Gene ◽  
Negative Energy ◽  
Receptor Expression ◽  
Melanocortin Receptor ◽  
Hypothalamic Nucleus ◽  
Hypothalamic Arcuate Nucleus ◽  
Ad Libitum ◽  
Peptide Gene ◽  
Plasma Leptin

Peripheral and hypothalamic mechanisms underlying the hyperphagia of lactation have been investigated in sheep. Sheep were fed ad libitum and killed at 6 and 18 days of lactation; ad libitum-fed nonlactating sheep were killed as controls. Despite increased food intake, lactating ewes were in negative energy balance. Lactation decreased plasma leptin and adipose tissue leptin mRNA concentrations. OB-Rb gene expression, determined by in situ hybridization, was increased in the hypothalamic arcuate nucleus (ARC) and ventromedial hypothalamic nucleus (VMH) at both stages of lactation. Neuropeptide Y (NPY) was increased by lactation in both the ARC and dorsomedial hypothalamus (DMH), although increased gene expression in the DMH was only apparent at day 18 of lactation. Gene expression was decreased for cocaine- and amphetamine-regulated transcript (CART) in the ARC and VMH and for proopiomelanocortin in ARC during lactation. Agouti-related peptide gene expression was increased in the ARC, and melanocortin receptor expression was unchanged in both the ARC and VMH with lactation. Thus the hypoleptinemia of lactation may activate NPY orexigenic pathways and attenuate anorexigenic melanocortin and CART pathways in the hypothalamus to promote the hyperphagia of lactation.

scholarly journals Neuropeptide Y gene expression in lines of mice subjected to long-term divergent selection on fat content

1999 ◽  
Vol 23 (1) ◽  
pp. 77-83 ◽  
Author(s):  
T Boswell ◽  
MA Nicholson ◽  
L Bunger
Keyword(s):  
Gene Expression ◽  
Neuropeptide Y ◽  
Fat Content ◽  
Sensitivity Threshold ◽  
Mrna Levels ◽  
Fat Percentage ◽  
Fed State ◽  
Ad Libitum ◽  
Plasma Leptin

Lines of mice have been developed in our laboratory by divergent long-term selection for body fat content. This has resulted in a fivefold (23% vs 4%) higher fat percentage in the Fat line at 14 weeks of age, with little difference between the Fat and Lean lines in fat-free body weight. As part of an approach to characterize the physiological mechanisms underlying these different phenotypes, neuropeptide Y (NPY) mRNA levels in the hypothalamus and cerebral cortex of ad libitum-fed and fasted mice of the Fat and Lean selected lines were measured. Significant differences in NPY gene expression were confined to the hypothalamus. Under ad libitum-fed conditions, hypothalamic NPY mRNA levels did not differ significantly between the Fat and Lean lines. After an overnight fast of 18-20 h, hypothalamic NPY mRNA levels were increased significantly (P<0.05) by 31% in Lean animals relative to fed mice from the same line. However, fasting did not significantly stimulate NPY gene expression in the Fat line. Most plasma leptin measurements in the Lean line fell below the sensitivity threshold of the assay (0.1 ng/ml), but levels in the Fat line were at least 30 to 50 times higher under fasted and fed conditions respectively. After fasting, plasma leptin levels in the Fat line decreased significantly (P<0. 05) by 48%. Thus, unlike the situation in other rodent models, obesity in the Fat line is not associated with increased hypothalamic NPY mRNA levels in the ad libitum-fed state. The decreased sensitivity of hypothalamic NPY gene expression to fasting in the Fat line is consistent with an inhibitory effect of higher circulating leptin levels.

scholarly journals Temporal changes in nutritional state affect hypothalamic POMC peptide levels independently of leptin in adult male mice

2014 ◽  
Vol 306 (8) ◽  
pp. E904-E915 ◽  
Author(s):  
Aaron J. Mercer ◽  
Ronald C. Stuart ◽  
Courtney A. Attard ◽  
Veronica Otero-Corchon ◽  
Eduardo A. Nillni ◽  
...  
Keyword(s):  
Energy Balance ◽  
Food Restriction ◽  
Fluorescent Protein ◽  
Negative Energy ◽  
Nutritional State ◽  
Melanocyte Stimulating Hormone ◽  
Reporter Mice ◽  
State Affect ◽  
Plasma Leptin ◽  
Chronic Food Restriction

Hypothalamic proopiomelanocortin (POMC) neurons constitute a critical anorexigenic node in the central nervous system (CNS) for maintaining energy balance. These neurons directly affect energy expenditure and feeding behavior by releasing bioactive neuropeptides but are also subject to signals directly related to nutritional state such as the adipokine leptin. To further investigate the interaction of diet and leptin on hypothalamic POMC peptide levels, we exposed 8- to 10-wk-old male POMC- Discosoma red fluorescent protein (DsRed) transgenic reporter mice to either 24–48 h (acute) or 2 wk (chronic) food restriction, high-fat diet (HFD), or leptin treatment. Using semiquantitative immunofluorescence and radioimmunoassays, we discovered that acute fasting and chronic food restriction decreased the levels of adrenocorticotropic hormone (ACTH), α-melanocyte-stimulating hormone (α-MSH), and β-endorphin in the hypothalamus, together with decreased DsRed fluorescence, compared with control ad libitum-fed mice. Furthermore, acute but not chronic HFD or leptin administration selectively increased α-MSH levels in POMC fibers and increased DsRed fluorescence in POMC cell bodies. HFD and leptin treatments comparably increased circulating leptin levels at both time points, suggesting that transcription of Pomc and synthesis of POMC peptide products are not modified in direct relation to the concentration of plasma leptin. Our findings indicate that negative energy balance persistently downregulated POMC peptide levels, and this phenomenon may be partially explained by decreased leptin levels, since these changes were blocked in fasted mice treated with leptin. In contrast, sustained elevation of plasma leptin by HFD or hormone supplementation did not significantly alter POMC peptide levels, indicating that enhanced leptin signaling does not chronically increase Pomc transcription and peptide synthesis.

scholarly journals Calorie Restriction Modulates Reproductive Development and Energy Balance in Pre-Pubertal Male Rats

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1993 ◽  
Author(s):  
Guilherme Rizzoto ◽  
Deepa Sekhar ◽  
Jacob C. Thundathil ◽  
Prasanth K. Chelikani ◽  
John P. Kastelic
Keyword(s):  
Body Composition ◽  
Energy Balance ◽  
Reproductive Development ◽  
Negative Energy ◽  
Male Rats ◽  
Plasma Testosterone ◽  
Feed Restriction ◽  
Testis Weight ◽  
Sprague Dawley ◽  
Ad Libitum

The objective was to determine effects of feed restriction and refeeding on reproductive development and energy balance in pre-pubertal male rats. Sprague Dawley rats (n = 32, 24 days old, ~65 g), were randomly allocated into four treatments (n = 8/treatment): (1) Control (CON, ad libitum feed; (2) Mild Restriction (MR, rats fed 75% of CON consumption); (3) Profound Restriction (PR, 50% of CON consumption); or (4) Refeeding (RF, 50% restriction for 14 days, and then ad libitum for 7 days). Feed restriction delayed reproductive development and decreased energy balance and tissue accretion, with degree of reproductive and metabolic dysfunctions related to restriction severity. In RF rats, refeeding largely restored testis weight, sperm production (per gram and total), plasma IGF-1, leptin and insulin concentrations and energy expenditure, although body composition did not completely recover. On Day 50, more CON and RF rats than PR rats were pubertal (5/6, 4/5 and 1/6, respectively; plasma testosterone >1 ng/mL) with the MR group (4/6) not different. Our hypothesis was supported: nutrient restriction of pre-pubertal rats delayed reproductive development, induced negative energy balance and decreased metabolic hormone concentrations (commensurate with restriction), whereas short-term refeeding after profound restriction largely restored reproductive end points and plasma hormone concentrations, but not body composition.

scholarly journals Estrogen-related receptor β deletion modulates whole-body energy balance via estrogen-related receptor γ and attenuates neuropeptide Y gene expression

2013 ◽  
Vol 37 (7) ◽  
pp. 1033-1047 ◽  
Author(s):  
Mardi S. Byerly ◽  
Muhannad Al Salayta ◽  
Roy D. Swanson ◽  
Kiwook Kwon ◽  
Jonathan M. Peterson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Energy Balance ◽  
Neuropeptide Y ◽  
Whole Body ◽  
Body Energy ◽  
Estrogen Related Receptor

Hypothalamic neuropeptide gene expression during recovery from food restriction superimposed on short-day photoperiod-induced weight loss in the Siberian hamster

2007 ◽  
Vol 293 (3) ◽  
pp. R1094-R1101 ◽  
Author(s):  
Zoë A. Archer ◽  
Kim M. Moar ◽  
Tracy J. Logie ◽  
Laura Reilly ◽  
Valerie Stevens ◽  
...  
Keyword(s):  
Gene Expression ◽  
Weight Loss ◽  
Energy Balance ◽  
Neuropeptide Y ◽  
Caloric Restriction ◽  
Neurotrophic Factor ◽  
Food Restriction ◽  
Brain Derived Neurotrophic Factor ◽  
Related Peptide ◽  
Short Day

Previously, 40% food restriction of male Siberian hamsters over 21 days in short-day (SD) photoperiod induced characteristic changes in expression of hypothalamic arcuate nucleus energy balance genes; mRNAs for neuropeptide Y, agouti-related peptide, and leptin receptor were upregulated, and those of proopiomelanocortin and cocaine- and amphetamine-regulated transcript were depressed. The present study examined the effect of refeeding hamsters for 6 days (∼50% recovery of weight differential) or 19 days (resumption of appropriate weight trajectory). Hyperphagia continued throughout refeeding, but differences in fat pad weights and leptin levels had disappeared after 19 days. Cocaine- and amphetamine-regulated transcript gene expression was depressed by prior restriction in both refed groups. The depressive effect of prior restriction on proopiomelanocortin gene expression had disappeared after 19 days of refeeding. There was no effect of prior food restriction on neuropeptide Y or agouti-related peptide gene expression. Expression of the anorexigenic brain-derived neurotrophic factor was downregulated in the ventromedial nucleus after SD exposure for 12 wk. In the SD food restriction study, there were effects of photoperiod on brain-derived neurotrophic factor gene expression but not of prior food restriction. Hypothalamic energy balance genes in the hamster respond asynchronously to return to a seasonally appropriate body weight. The achievement of this weight rather than the weight at which caloric restriction was imposed is the critical factor. The differential responses of hypothalamic energy balance genes to food restriction and refeeding are poorly characterized in any species, a critical issue given their potential relevance to human weight loss strategies that involve caloric restriction.

scholarly journals Intermittent Fasting Promotes Fat Loss With Lean Mass Retention, Increased Hypothalamic Norepinephrine Content, and Increased Neuropeptide Y Gene Expression in Diet-Induced Obese Male Mice

Endocrinology ◽  
2015 ◽  
Vol 157 (2) ◽  
pp. 679-691 ◽  
Author(s):  
Juliet D. Gotthardt ◽  
Jessica L. Verpeut ◽  
Bryn L. Yeomans ◽  
Jennifer A. Yang ◽  
Ali Yasrebi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Weight Loss ◽  
Neuropeptide Y ◽  
Lean Mass ◽  
Area Under The Curve ◽  
Intermittent Fasting ◽  
Oral Glucose ◽  
Tissue Homogenates ◽  
Ad Libitum ◽  
The Imf

Abstract Clinical studies indicate alternate-day, intermittent fasting (IMF) protocols result in meaningful weight loss in obese individuals. To further understand the mechanisms sustaining weight loss by IMF, we investigated the metabolic and neural alterations of IMF in obese mice. Male C57/BL6 mice were fed a high-fat diet (HFD; 45% fat) ad libitum for 8 weeks to promote an obese phenotype. Mice were divided into four groups and either maintained on ad libitum HFD, received alternate-day access to HFD (IMF-HFD), and switched to ad libitum low-fat diet (LFD; 10% fat) or received IMF of LFD (IMF-LFD). After 4 weeks, IMF-HFD (∼13%) and IMF-LFD (∼18%) had significantly lower body weights than the HFD. Body fat was also lower (∼40%–52%) in all diet interventions. Lean mass was increased in the IMF-LFD (∼12%–13%) compared with the HFD and IMF-HFD groups. Oral glucose tolerance area under the curve was lower in the IMF-HFD (∼50%), whereas the insulin tolerance area under the curve was reduced in all diet interventions (∼22%–42%). HPLC measurements of hypothalamic tissue homogenates indicated higher (∼55%–60%) norepinephrine (NE) content in the anterior regions of the medial hypothalamus of IMF compared with the ad libitum-fed groups, whereas NE content was higher (∼19%–32%) in posterior regions in the IMF-LFD group only. Relative gene expression of Npy in the arcuate nucleus was increased (∼65%–75%) in IMF groups. Our novel findings indicate that intermittent fasting produces alterations in hypothalamic NE and neuropeptide Y, suggesting the counterregulatory processes of short-term weight loss are associated with an IMF dietary strategy.

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