scholarly journals PSXIII-31 Hypothalamic and pituitary responses to resistin in sheep: integration of resistin and leptin signaling involving SOCS-3 and LepRb

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 364-364
Author(s):  
Dorota A Zieba ◽  
Weronika Biernat ◽  
Malgorzata Szczesna ◽  
Katarzyna Kirsz ◽  
Tomasz Misztal
Keyword(s):  
Low Dose ◽  
Arcuate Nucleus ◽  
Preoptic Area ◽  
Leptin Resistance ◽  
High Dose ◽  
Leptin Signaling ◽  
Hypothalamic Nuclei ◽  
Natural Photoperiod ◽  
Tissue Sensitivity ◽  
Short Days

Abstract Leptin and resistin play important roles in regulating body weight and glucose metabolism. Herein, we hypothesized that resistin is a factor leading to decreased tissue sensitivity to leptin through effects on SOCS-3 and LeptRb expression. Expression of SOCS-3 and LeptRb were determined using Real-Time PCR in selected brain tissues: arcuate nucleus (ARC), ventro- and dorsomedial nuclei (VMH/DMH), preoptic area (POA) and anterior pituitary (AP). Thirty ewes (10/group), ovariectomized with E2-replacement, were fed ad libitum and housed under natural photoperiod. Intravenous treatments consisted of 1) control, 2) low dose of rbresistin (R1; 1.0 μg/kg BW), and 3) high dose of rbresistin (R2; 10.0 μg/kg BW). During long days (LD), LeptRb transcript in ARC decreased in response to R2 (P < 0.001) compared to Control. Expression of LeptRb in VMH/DMH decreased in response to R1(P < 0.001) and R2 (P < 0.001) during short days (SD) and to R2 (P < 0.001) during LD. Conversely, LeptrB transcript increased (P < 0.001) 8-fold in R1 and 4-fold in R2 (P < 0.05) in POA during SD. LeptrB transcript in the AP increased (P < 0.001) 2.1- and 1.8-fold, respectively, in response to R1 and R2 during LD. Within the ARC, SOCS-3 expression increased (P < 0.001) after R2 in LD. In POA, a 2.3-fold (P < 0.001) increase was noted in R2 only during LD. Moreover, SOCS-3 transcript increased in the AP during both LD (8.5-fold) and SD (5.8-fold) in response to R2 (P < 0.001). Evidence indicates that resistin resulted in a consistent decrease in LeptRb (except POA) and increase in SOCS-3 expression during LD in all hypothalamic nuclei. In AP, resistin increased SOCS-3 during both LD and SD and LeptRb transcript during LD. Taken together, the effects of resistin appear to be strongly associated with photoperiod-driven changes in the leptin signaling pathway, which may underlie the phenomenon of leptin resistance.

scholarly journals Seasonal and Nutritional Fluctuations in the mRNA Levels of the Short Form of the Leptin Receptor (LRa) in the Hypothalamus and Anterior Pituitary in Resistin-Treated Sheep

Animals ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 2451
Author(s):  
Weronika Biernat ◽  
Malgorzata Szczęsna ◽  
Katarzyna Kirsz ◽  
Dorota Anna Zieba
Keyword(s):  
Anterior Pituitary ◽  
Arcuate Nucleus ◽  
Leptin Receptor ◽  
Preoptic Area ◽  
Short Form ◽  
Leptin Resistance ◽  
Mrna Levels ◽  
Mrna Transcript ◽  
The Central Nervous System ◽  
Short Days

The short form of the leptin receptor (LRa) plays a key role in the transport of leptin to the central nervous system (CNS). Here, the resistin (RSTN)-mediated expression of LRa in the preoptic area (POA), ventromedial and dorsomedial nuclei (VMH/DMH),arcuate nucleus (ARC) and the anterior pituitary gland (AP)was analyzed considering the photoperiodic (experiment 1) and nutritional status (experiment 2) of ewes. In experiment 1, 30 sheep were fed normally and received one injection of saline or two doses of RSTN one hour prior to euthanasia. RSTN increased LRa expression mainly in the ARC and AP during long days (LD) and only in the AP during short days (SD). In experiment 2, an altered diet for 5 months created lean or fat sheep. Twenty sheep were divided into four groups: the lean and fat groups were given saline, while the lean-R and fat-R groups received RSTN one hour prior to euthanasia. Changes in adiposity influenced the effect of RSTN on LRa mRNA transcript levels in the POA, ARC and AP and without detection of LRa in the VMH/DMH. Overall, both photoperiodic and nutritional signals influence the effects of RSTN on leptin transport to the CNS and are involved in the adaptive/pathological phenomenon of leptin resistance in sheep.

scholarly journals Region-Specific Reduction in Leptin-Induced Phosphorylation of Signal Transducer and Activator of Transcription-3 (STAT3) in the Rat Hypothalamus Is Associated with Leptin Resistance during Pregnancy

Endocrinology ◽  
2004 ◽  
Vol 145 (8) ◽  
pp. 3704-3711 ◽  
Author(s):  
S. R. Ladyman ◽  
D. R. Grattan
Keyword(s):  
Food Intake ◽  
Arcuate Nucleus ◽  
Ventromedial Hypothalamus ◽  
Leptin Resistance ◽  
Signal Transducer ◽  
Pregnant Rats ◽  
Hypothalamic Nuclei ◽  
Stat3 Phosphorylation ◽  
Vehicle Treatment ◽  
Plasma Leptin

Abstract Leptin concentrations increase during pregnancy, but this does not prevent the pregnancy-induced increase in food intake, suggesting a state of leptin resistance. This study investigated the response to intracerebroventricular leptin administration in pregnant rats. After fasting, nonpregnant, d-7 and d-14 pregnant rats received leptin (4 μg) or vehicle, then food intake was measured. Serial blood samples were collected in another group of rats to determine plasma leptin concentrations. Further groups of d-14 pregnant and nonpregnant rats were killed after leptin or vehicle treatment, and brains were collected. Hypothalamic nuclei were microdissected, and levels of signal transducer and activator of transcription (STAT)3 phosphorylation were measured using Western blot analysis. Fasting decreased leptin concentrations in both pregnant and nonpregnant rats. Leptin treatment significantly reduced food intake in nonpregnant and d-7 pregnant rats but not in d-14 pregnant rats. In addition, there was no postfasting hyperphagic response in the pregnant rats. In the pregnant rats, leptin-induced STAT3 phosphorylation was suppressed in the arcuate nucleus and, to a lesser extent, in the ventromedial hypothalamus (VMH), compared with nonpregnant rats. Unstimulated STAT3 levels were also decreased in the VMH during pregnancy. Leptin-induced phosphorylation of STAT3 in the dorsomedial and lateral hypothalamus was not different between pregnant and nonpregnant rats. These data indicate that pregnant rats become resistant to the satiety action of leptin. Furthermore, leptin-induced activation of the STAT3 is impaired during pregnancy, specifically in the arcuate nucleus and VMH. These data support the hypothesis that pregnancy is a state of hypothalamic leptin resistance.

Hypothalamic mapping of orexigenic action and Fos-like immunoreactivity following relaxin-3 administration in male Wistar rats

2007 ◽  
Vol 292 (3) ◽  
pp. E913-E919 ◽  
Author(s):  
B. M. McGowan ◽  
S. A. Stanley ◽  
N. E. White ◽  
A. Spangeus ◽  
M. Patterson ◽  
...  
Keyword(s):  
Food Intake ◽  
Supraoptic Nucleus ◽  
Arcuate Nucleus ◽  
Preoptic Area ◽  
Disulphide Bonds ◽  
Hypothalamic Nuclei ◽  
Relaxin Family ◽  
Male Wistar Rats ◽  
Additional Support ◽  
G Protein Coupled

The insulin superfamily, characterized by common disulphide bonds, includes not only insulin but also insulin-like peptides such as relaxin-1 and relaxin-3. The actions of relaxin-3 are largely unknown, but recent work suggests a role in regulation of food intake. Relaxin-3 mRNA is highly expressed in the nucleus incertus, which has extensive projections to the hypothalamus, and relaxin immunoreactivity is present in several hypothalamic nuclei. In the rat, relaxin-3 binds and activates both relaxin family peptide receptor 1, which also binds relaxin-1, and a previously orphaned G protein-coupled receptor, RXFP3. These receptors are extensively expressed in the hypothalamus. The aims of these studies were twofold: 1) map the hypothalamic site(s) of the orexigenic action of relaxin-3 and 2) examine the site(s) of neuronal activation following central relaxin-3 administration. After microinjection into hypothalamic sites, human relaxin-3 (H3; 180 pmol) significantly stimulated 0- to 1-h food intake in the supraoptic nucleus (SON), arcuate nucleus (ARC), and the anterior preoptic area (APOA) [SON 0.4 ± 0.2 (vehicle) vs. 2.9 ± 0.5 g (H3), P < 0.001; ARC 0.7 ± 0.3 (vehicle) vs. 2.7 ± 0.2 g (H3), P < 0.05; and APOA 0.8 ± 0.1 (vehicle) vs. 2.2 ± 0.2 g (H3), P < 0.05]. Cumulative food intake was significantly increased ≤8 h following administration into the SON and 4 h into the APOA. A significant increase in Fos-like immunoreactivity was seen in the SON following central relaxin-3 administration. Relaxin-3 stimulates feeding in several hypothalamic nuclei, and these studies provide additional support for relaxin-3 as an important peptide in appetite regulation.

Hypothyroidism Induces Hypophagia Associated with Alterations in Protein Expression of Neuropeptide Y and Proopiomelanocortin in the Arcuate Nucleus, Independently of Hypothalamic Nuclei-Specific Changes in Leptin Signaling

Thyroid ◽  
2016 ◽  
Vol 26 (1) ◽  
pp. 134-143 ◽  
Author(s):  
Camila Calvino ◽  
Güínever Eustáquio Império ◽  
Marianna Wilieman ◽  
Ricardo Henrique Costa-e-Sousa ◽  
Luana Lopes Souza ◽  
...  
Keyword(s):  
Protein Expression ◽  
Neuropeptide Y ◽  
Arcuate Nucleus ◽  
Leptin Signaling ◽  
Hypothalamic Nuclei

scholarly journals Endogenous VMH amylin signaling is required for full leptin signaling and protection from diet-induced obesity

2016 ◽  
Vol 310 (4) ◽  
pp. R355-R365 ◽  
Author(s):  
Ambrose A. Dunn-Meynell ◽  
Christelle Le Foll ◽  
Miranda D. Johnson ◽  
Thomas A. Lutz ◽  
Matthew R. Hayes ◽  
...  
Keyword(s):  
Ventromedial Hypothalamus ◽  
Tolerance Test ◽  
Leptin Resistance ◽  
Oral Glucose ◽  
Dorsomedial Nucleus ◽  
Adeno Associated Virus ◽  
Leptin Signaling ◽  
Insulin Resistant ◽  
Diet Induced Obesity ◽  
Hypothalamic Nuclei

Amylin enhances arcuate (ARC) and ventromedial (VMN) hypothalamic nuclei leptin signaling and synergistically reduces food intake and body weight in selectively bred diet-induced obese (DIO) rats. Since DIO 125I-amylin dorsomedial nucleus-dorsomedial VMN binding was reduced, we postulated that this contributed to DIO ventromedial hypothalamus (VMH) leptin resistance, and that impairing VMH (ARC + VMN) calcitonin receptor (CTR)-mediated signaling by injecting adeno-associated virus (AAV) expressing a short hairpin portion of the CTR mRNA would predispose diet-resistant (DR) rats to obesity on high-fat (45%) diet (HFD). Depleting VMH CTR by 80–90% in 4-wk-old male DR rats reduced their ARC and VMN 125I-labeled leptin binding by 57 and 51%, respectively, and VMN leptin-induced phospho-signal transducer and activator of transcription 3-positive neurons by 59% vs. AAV control rats. After 6 wk on chow, VMH CTR-depleted DR rats ate and gained the equivalent amount of food and weight but had 18% heavier fat pads (relative to carcass weight), 144% higher leptin levels, and were insulin resistant compared with control AAV DR rats. After 6 wk more on HFD, VMH CTR-depleted DR rats ate the same amount but gained 28% more weight, had 60% more carcass fat, 254% higher leptin levels, and 132% higher insulin areas under the curve during an oral glucose tolerance test than control DR rats. Therefore, impairing endogenous VMH CTR-mediated signaling reduced leptin signaling and caused DR rats to become more obese and insulin resistant, both on chow and HFD. These results suggest that endogenous VMH amylin signaling is required for full leptin signaling and protection from HFD-induced obesity.

scholarly journals Fourth-ventricle leptin infusions dose-dependently activate hypothalamic signal transducer and activator of transcription 3

2016 ◽  
Vol 311 (6) ◽  
pp. E939-E948 ◽  
Author(s):  
Ruth B. S. Harris ◽  
Bhavna N. Desai
Keyword(s):  
Weight Loss ◽  
Energy Balance ◽  
Food Intake ◽  
Fourth Ventricle ◽  
Low Dose ◽  
High Dose ◽  
Rapid Weight Loss ◽  
Leptin Signaling ◽  
Leptin Receptors ◽  
Arcuate Nuclei

Previous studies have shown that very low-dose infusions of leptin into the third or the fourth ventricle alone have little effect on energy balance, but simultaneous low-dose infusions cause rapid weight loss and increased phosphorylation of STAT3 (p-STAT3) in hypothalamic sites that express leptin receptors. Other studies show that injecting high doses of leptin into the fourth ventricle inhibits food intake and weight gain. Therefore, we tested whether fourth-ventricle leptin infusions that cause weight loss are associated with increased leptin signaling in the hypothalamus. In a dose response study 14-day infusions of increasing doses of leptin showed significant hypophagia, weight loss, and increased hypothalamic p-STAT3 in rats receiving at least 0.9 μg leptin/day. In a second study 0.6 μg leptin/day transiently inhibited food intake and reduced carcass fat, but had no significant effect on energy expenditure. In a final study, we identified the localization of STAT3 activation in the hypothalamus of rats receiving 0, 0.3, or 1.2 μg leptin/day. The high dose of leptin, which caused weight loss in the first experiment, increased p-STAT3 in the ventromedial, dorsomedial, and arcuate nuclei of the hypothalamus. The low dose that increased brown fat UCP1 but did not affect body composition in the first experiment had little effect on hypothalamic p-STAT3. We propose that hindbrain leptin increases the precision of control of energy balance by lowering the threshold for leptin signaling in the forebrain. Further studies are needed to directly test this hypothesis.

Increased neuropeptide Y content in individual hypothalamic nuclei, but not neuropeptide Y mRNA, in diet-induced obesity in rats

1992 ◽  
Vol 132 (2) ◽  
pp. 299-304 ◽  
Author(s):  
J. P. H. Wilding ◽  
S. G. Gilbey ◽  
M. Mannan ◽  
N. Aslam ◽  
M. A. Ghatei ◽  
...  
Keyword(s):  
Neuropeptide Y ◽  
Northern Blot Analysis ◽  
Arcuate Nucleus ◽  
Preoptic Area ◽  
Chronic Administration ◽  
Northern Blotting ◽  
Physiological Importance ◽  
Diet Induced Obesity ◽  
Hypothalamic Nuclei ◽  
Palatable Diet

ABSTRACT Neuropeptide Y (NPY) is the most powerful appetite stimulant known, and chronic administration leads to obesity. The hypothalamic content of NPY varies with nutritional status, suggesting that it is of physiological importance. We measured NPY in specific hypothalamic nuclei and NPY mRNA in the hypothalamus by Northern blotting in rats made obese by feeding a highly palatable diet compared with controls fed standard chow. In animals fed the palatable diet, NPY concentrations were increased in the paraventricular nucleus (mean ± s.e.m.; 19·5 ± 2·3 vs 11·1 ± 1·1 fmol/μg protein, P < 0·02), the arcuate nucleus (20·4 ± 3·3 vs 9·3 ± 0·6 fmol/μg protein, P < 0·01), the medial preoptic area (9·1 ± 0·9 vs 5·9 ± 0·7 fmol/μg protein, P < 0·02) and the anterior hypothalamus (2·7 ± 0·2 vs 2·0 ± 0·1 fmol/μg, P < 0·02). Hypothalamic NPY mRNA measured by Northern blot analysis was, however, unchanged. These results suggest that the increase in NPY was due to decreased release rather than increased NPYergic activity. The findings are in accord with the neuroendocrine disturbance and increased thermogenesis observed in this model of obesity. Journal of Endocrinology (1992) 132, 299–304

scholarly journals Neonatal exposure to bisphenol A modifies the abundance of estrogen receptor α transcripts with alternative 5′-untranslated regions in the female rat preoptic area

2007 ◽  
Vol 194 (1) ◽  
pp. 201-212 ◽  
Author(s):  
Lucas Monje ◽  
Jorgelina Varayoud ◽  
Enrique H Luque ◽  
Jorge G Ramos
Keyword(s):  
Estrogen Receptor ◽  
Bisphenol A ◽  
Low Dose ◽  
Preoptic Area ◽  
Methylation Status ◽  
Estrogen Receptor Α ◽  
Female Rats ◽  
Untranslated Regions ◽  
Neonatal Exposure ◽  
High Dose

The xenoestrogen bisphenol A (BPA) is commonly ingested by humans. We examined the effects of neonatal exposure to low versus high doses of BPA over the control of estrogen receptor α (ERα) expression in the preoptic area (POA) of prepubertal female rats. Pups received s.c. injections every 48 h of BPA (high dose, 20 mg/kg and low dose, 0.05 mg/kg) or diethylstilbestrol (DES, 0.02 mg/kg) from postnatal day (PND) 1 to PND7 and were killed at PND8 or PND21. Relative expression of ERα transcripts containing alternative 5′-untranslated regions OS, ON, O, OT, and E1 in POA were evaluated by RT-PCR. Methylation status of ERα promoters was determined by bisulfited DNA restriction analysis and ERα protein by immunohistochemistry. In PND8, the high dose of BPA and DES diminished total ERα mRNA levels, mediated by the decreased expression of ERα-O and ERα-OT variants. In contrast, the low dose of BPA augmented total ERα mRNA by increasing the expression of the ERα-E1 variant. In PND21, both BPA doses increased total ERα mRNA by means of the augmented expression of ERα-O and ERα-OT variants. In PND21, the methylation status of the ERα promoters and the circulating levels of estradiol were similar in all experimental groups. At PND8 and PND21, DES and the high dose of BPA decreased, while the low dose of BPA increased ERα protein in the POA. These findings show that neonatal BPA exposure alters the abundance of hypothalamic ERα transcript variants and protein in a dose-dependent manner.

scholarly journals Peptide YY3–36 and Glucagon-Like Peptide-17–36 Inhibit Food Intake Additively

Endocrinology ◽  
2005 ◽  
Vol 146 (12) ◽  
pp. 5120-5127 ◽  
Author(s):  
Nicola M. Neary ◽  
Caroline J. Small ◽  
Maralyn R. Druce ◽  
Adrian J. Park ◽  
Sandra M. Ellis ◽  
...  
Keyword(s):  
Food Intake ◽  
Brain Stem ◽  
Low Dose ◽  
Arcuate Nucleus ◽  
Peptide Yy ◽  
High Dose ◽  
Hypothalamic Arcuate Nucleus ◽  
Inhibit Food Intake ◽  
Glucagon Like Peptide ◽  
The Brain

Peptide YY (PYY) and glucagon like peptide (GLP)-1 are cosecreted from intestinal L cells, and plasma levels of both hormones rise after a meal. Peripheral administration of PYY3–36 and GLP-17–36 inhibit food intake when administered alone. However, their combined effects on appetite are unknown. We studied the effects of peripheral coadministration of PYY3–36 with GLP-17–36 in rodents and man. Whereas high-dose PYY3–36 (100 nmol/kg) and high-dose GLP-17–36 (100 nmol/kg) inhibited feeding individually, their combination led to significantly greater feeding inhibition. Additive inhibition of feeding was also observed in the genetic obese models, ob/ob and db/db mice. At low doses of PYY3–36 (1 nmol/kg) and GLP-17–36 (10 nmol/kg), which alone had no effect on food intake, coadministration led to significant reduction in food intake. To investigate potential mechanisms, c-fos immunoreactivity was quantified in the hypothalamus and brain stem. In the hypothalamic arcuate nucleus, no changes were observed after low-dose PYY3–36 or GLP-17–36 individually, but there were significantly more fos-positive neurons after coadministration. In contrast, there was no evidence of additive fos-stimulation in the brain stem. Finally, we coadministered PYY3–36 and GLP-17–36 in man. Ten lean fasted volunteers received 120-min infusions of saline, GLP-17–36 (0.4 pmol/kg·min), PYY3–36 (0.4 pmol/kg·min), and PYY3–36 (0.4 pmol/kg·min) + GLP-17–36 (0.4 pmol/kg·min) on four separate days. Energy intake from a buffet meal after combined PYY3–36 + GLP-17–36 treatment was reduced by 27% and was significantly lower than that after either treatment alone. Thus, PYY3–36 and GLP-17–36, cosecreted after a meal, may inhibit food intake additively.

Acetaminophen: Neonatal hepatotoxicity due to late pregnancy exposure

1987 ◽  
Vol 45 ◽  
pp. 718-719
Author(s):  
G.A. Miranda ◽  
M.A. Arroyo ◽  
C.A. Lucio ◽  
M. Mongeotti ◽  
S.S. Poolsawat
Keyword(s):  
Low Dose ◽  
Fetal Liver ◽  
Late Pregnancy ◽  
Toxic Chemicals ◽  
Control Group ◽  
High Dose ◽  
Over The Counter ◽  
Liver And Kidney ◽  
Neonatal Liver ◽  
Childbearing Women

Exposure to drugs and toxic chemicals, during late pregnancy, is a common occurrence in childbearing women. Some studies have reported that more than 90% of pregnant women use at least 1 prescription; of this, 60% used more than one. Another study indicated that 80% of the consumed drugs were not prescribed, and of this figure, 95% were “over-the-counter” drugs. Acetaminophen, the safest of all over-the-counter drugs, has been reported to induce fetal liver necrosis in man and animals and to have abortifacient and embryocidal action in mice. This study examines the degree to which acetaminophen affects the neonatal liver and kidney, when a fatty diet is simultaneously fed to the mother during late pregnancy.Timed Swiss Webster female mice were gavaged during late pregnancy (days 16-19) with fat suspended acetaminophen at a high dose, HD = 84.50 mg/kg, and a low dose, LD = 42.25 mg/kg; a control group received fat alone.

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