scholarly journals Role of SOCS3 in POMC neurons in metabolic and cardiovascular regulation

2019 ◽  
Vol 316 (4) ◽  
pp. R338-R351 ◽  
Author(s):  
Zhen Wang ◽  
Jussara M. do Carmo ◽  
Alexandre A. da Silva ◽  
Kandice C. Bailey ◽  
Nicola Aberdein ◽  
...  
Keyword(s):  
Heart Rate ◽  
Body Weight ◽  
Food Intake ◽  
Stress Test ◽  
Control Diet ◽  
Negative Regulator ◽  
Cytokine Signaling ◽  
Male And Female ◽  
Air Jet ◽  
And Control

Suppressor of cytokine signaling 3 (SOCS3) is a negative regulator of leptin signaling. We previously showed that the chronic effects of leptin on blood pressure (BP) and glucose regulation are mediated by stimulation of proopiomelanocortin (POMC) neurons. In this study we examined the importance of endogenous SOCS3 in POMC neurons in control of metabolic and cardiovascular function and potential sex differences. Male and female SOCS3flox/flox/POMC-Cre mice in which SOCS3 was selectively deleted in POMC neurons and control SOCS3flox/flox mice were studied during a control diet (CD) or a high-fat diet (HFD) and during chronic leptin infusion. Body weight was lower in male and female SOCS3flox/flox/POMC-Cre than control mice fed the CD, despite similar food intake. Male SOCS3flox/flox/POMC-Cre mice exhibited increased energy expenditure. BP and heart rate were similar in male and female SOCS3flox/flox/POMC-Cre and control mice fed the CD. HFD-fed male and female SOCS3flox/flox/POMC-Cre mice showed attenuated weight gain. HFD-induced elevations in baseline BP and BP responses to an air-jet stress test were greater in female SOCS3flox/flox/POMC-Cre than control mice. Chronic leptin infusion produced similar responses for food intake, body weight, oxygen consumption, blood glucose, BP, and heart rate in all groups. Thus SOCS3 deficiency in POMC neurons influences body weight regulation in the setting of CD and HFD and differentially affects BP and energy balance in a sex-specific manner but does not amplify the dietary, glycemic, or cardiovascular effects of leptin.

Abstract P076: Suppressor of Cytokine Signaling 3 (SOCS3) in POMC Neurons and Its Role in Regulating Blood Pressure, Body Weight and Glucose in Obesity

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Zhen Wang ◽  
Jussara M do Carmo ◽  
Alexandre A da Silva ◽  
John E Hall
Keyword(s):  
Blood Pressure ◽  
Body Weight ◽  
Food Intake ◽  
Negative Regulator ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
Male And Female ◽  
Female Mice ◽  
And Control

Suppressor of cytokine signaling 3 (SOCS3), a negative regulator of leptin signaling, may be involved in development of obesity-induced leptin resistance. Although we previously showed that activation of proopiomelanocortin (POMC) neurons mediates the chronic effects of leptin on blood pressure (BP), the role of SOCS3 in modulating BP in obesity is still unclear. In this study, we investigated the role of SOCS3 specifically in POMC neurons in regulating body weight, glucose handling and BP in mice fed a normal or high fat (45%, HFD) chow. Male and female SOCS3flox/flox-POMC/cre mice in which SOCS3 was selectively deleted in POMC neurons and control SOCS3flox/flox mice were used. Food intake and body weight were measured from 8 to 16 weeks of age, and a glucose tolerance test (GTT) was performed at 20 wks of age. At 22 wks of age, mice were implanted with telemetry probe to measure BP and heart rate (HR) and fed a HFD for 6 weeks. Compared to control mice, both male and female SOCS3flox/flox-POMC/cre mice were lighter at 16 wks (29.1 ± 3.5 vs 31.9 ± 3.6 g in male and 21.5 ± 2.2 vs 26.1 ± 5.7 in female, n=9-11, p<0.05) but food intake was similar in both groups. Only male SOCS3flox/flox-POMC/cre mice exhibited improved glucose handling (AUC: 1059 ± 52 vs 1283 ± 54 mg/dL x 120 min, n=7-10, p<0.05 ) and no differences were observed in female mice. When fed normal chow, BP was similar in SOCS3flox/flox-POMC/cre and control mice (116 ± 7 vs 113 ± 5 mmHg) at 23 wks. After a HFD for 6 weeks, SOCS3flox/flox-POMC/cre mice had a greater BP increase compared to control mice (7.2 ± 1.9 vs 0.9 ± 1.8 mmHg, n=4-9, P<0.05) but no significant differences were observed in food intake or body weight between two groups. These results suggest that SOCS3 deletion specifically in POMC neurons reduced body weight in male and female mice, and improved glucose handling only in male mice. HFD increased BP in SOCS3flox/flox-POMC/cre but not in control mice, suggesting that SOCS3 in POMC neurons may modulate BP response to HFD.

Abstract 077: Role of Suppressor of Cytokines Signaling 3 (SOCS3) in POMC Neurons in Regulating Metabolic and Cardiovascular Functions in Dietary-Induced Obesity

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Zhen Wang ◽  
Jussara do Carmo ◽  
Alexandre da Silva ◽  
Nicola Aberdein ◽  
John Hall
Keyword(s):  
Food Intake ◽  
Glucose Tolerance ◽  
Body Weight Gain ◽  
Negative Regulator ◽  
Leptin Resistance ◽  
Cytokine Signaling ◽  
Male And Female ◽  
Air Jet ◽  
Cardiovascular Functions

Suppressor of cytokine signaling 3 (SOCS3), a negative regulator of leptin signaling, may contribute to the development of obesity-induced leptin resistance. Previously, we showed that activation of proopiomelanocortin (POMC) neurons mediates the chronic effects of leptin on blood pressure (BP) and glucose regulation. However, the role of SOCS3 in POMC neurons in regulating metabolic and cardiovascular functions in obesity is still unclear. To address this question, we used male and female mice with SOCS3 deleted only in POMC neurons (SOCS3 flox/flox -POMC/cre) and flox control (SOCS3 flox/flox ) mice. After weaning, mice were fed normal chow until 20 wks of age; then glucose tolerance tests (GTT) were performed and telemetry probes were implanted to measure mean arterial pressure (MAP) 24-hrs/day. We found that at 23 wks of age, both male and female SOCS3 flox/flox -POMC/cre mice weighed less than control mice (32±1 vs 37±2 g in male and 25±1 vs 27±1 g in female, n=9-11, p <0.05), but had similar daily food intake (3.5±0.2 g in male and 3.3±0.1 g in female) and MAP (114±1 vs 115±2 mmHg). Only male SOCS3 flox/flox -POMC/cre mice exhibited improved glucose tolerance (AUC: 1059±52 vs 1283±54 mg/dL x 120 min, n=7-10, p <0.05) compared to controls. From 23 wks, mice were switched to a high fat diet (45%, HFD) for 6 wks. After HFD feeding, both male and female SOCS3 flox/flox -POMC/cre mice had slightly reduced food intake (3.2±0.1 vs 3.5±0.2 g in male and 2.7±0.1 vs 3.0±0.2 g in female) and a trend toward lower body weight gain (10±1 vs 12±1 g in male and 4±1 vs 6±1 g in female), although the differences were not significant compared to controls. However, male and female SOCS3 flox/flox -POMC/cre mice fed a HFD had significantly greater MAP increase (7±1 vs 1±1 mmHg, n=13-16, p <0.05) and an enhanced BP response to acute air-jet stress (AUC: 109±9 vs 74±12 mmHg x 5min, n=8-13, p <0.05). After HFD, glucose tolerance was impaired in all groups of mice compared to the baseline at 20 wks, but there were no differences between SOCS3 flox/flox -POMC/cre and controls. These results suggest that deletion of SOCS3 in POMC neurons amplifies the BP response to a HFD and to acute stress, but has minimal effects on metabolic functions to HFD. (NHLBI PO1HL51971, NIGMS P20GM104357, AHA 14POST18160019)

scholarly journals THE EFFECT OF AMORPHOPHALLUS MUELLERI BLUME AND MORINGA OLEIFERA L LEAVES ON BODY WEIGHT, FEED INTAKE, AND HEPATIC HISTOPATHOLOGY IN MICE

2021 ◽  
pp. 82-87
Author(s):  
DIAN RATIH LAKSMITAWATI ◽  
UMI MARWATI ◽  
YATI SUMIYATI ◽  
DIAH KARTIKA PRATAMI ◽  
INTAN PERMATA SARI
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Feed Intake ◽  
Moringa Oleifera ◽  
Control Diet ◽  
Total Food Intake ◽  
Total Food ◽  
Lower Body Weight ◽  
And Control ◽  
Hepatic Histopathology

Objective: This study aims to determine the effect of Amorphophallus muelleri Blume and Moringa oleifera L leaf on body weight, food intake, and hepatic histopathology in mice. Methods: The mice were divided into five groups according to their diet, which includes porang, wheat, porang-moringa, wheat-moringa, and control diet. Each group consists of 5 males and 5 females, which were fed for 28 d, and then analyzed for their body weight, total food intake, alanine aminotransferase (ALT) as well as aspartate aminotransferase (AST) levels in plasma, and hepatic histopathology. Results: The result showed that the group of porang and porang-moringa has lower body weight and feed intake, which is significantly different compared to the others. Furthermore, an increase was observed on plasma AST/ALT activities in 30% porang and 20% porang-moringa group. Also, one of the mice of porang group has inflammatory cell infiltration (++) on histopathology results. Conclusion: It was therefore concluded that feeding containing porang causes low food consumption. Furthermore, weight loss increases AST/ALT and leukocyte infiltration even though a mouse consistently deteriorates.

Deletion of PTP 1B from Brain Neurons Partly Protects Mice from Diet-Induced Obesity and Minimally Improves Fertility

Endocrinology ◽  
2021 ◽  
Author(s):  
Caroline M Ancel ◽  
Maggie C Evans ◽  
Romy I Kerbus ◽  
Elliot G Wallace ◽  
Greg M Anderson
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Glucose Tolerance ◽  
Knockout Mice ◽  
Body Weight Gain ◽  
Negative Regulator ◽  
Cytokine Signaling ◽  
Male And Female ◽  
Female Mice ◽  
Calorie Diet

Abstract Reproductive dysfunction in women has been linked to high calorie diet (HCD)-feeding and obesity. Central resistance to leptin and insulin have been shown to accompany diet-induced infertility in rodent studies, and we have previously shown that deleting suppressor of cytokine signaling 3, which is a negative regulator of leptin signaling, from all forebrain neurons partially protects mice from HCD-induced infertility. In this study, we were interested in exploring the role of protein tyrosine phosphatase 1B (PTP1B), which is a negative regulator of both leptin and insulin signaling, in the pathophysiology of HCD-induced obesity and infertility. To this end, we generated male and female neuron-specific PTP1B knockout mice and compared their body weight gain, food intake, glucose tolerance and fertility to control littermates under both normal calorie diet-feeding and HCD-feeding conditions. Both male and female mice with neuronal PTP1B deletion exhibited slower body weight gain in response to HCD-feeding, yet only male knockout mice exhibited improved glucose tolerance compared with controls. Neuronal PTP1B deletion improved the time to first litter in HCD-fed mice, but did not protect female mice from eventual HCD-induced infertility. While the mice fed a normal caloric diet remained fertile throughout the 150 day period of assessment, HCD-fed females became infertile after producing only a single litter, regardless of their genotype. These data show that neuronal PTP1B deletion is able to partially protect mice from HCD-induced obesity, but is not a critical mediator of HCD-induced infertility.

scholarly journals Feeding spinach thylakoids to rats modulates the gut microbiota, decreases food intake and affects the insulin response

2013 ◽  
Vol 2 ◽  
Author(s):  
Caroline Montelius ◽  
Nadia Osman ◽  
Björn Weström ◽  
Siv Ahrné ◽  
Göran Molin ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Glucose Tolerance ◽  
Gut Microbiota ◽  
Glucose Tolerance Test ◽  
Control Diet ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Microbial Composition ◽  
And Control

AbstractThylakoid membranes derived from green leaf chloroplasts affect appetite-regulating hormones, suppress food intake, reduce blood lipids and lead to a decreased body weight in animals and human subjects. Thylakoids also decrease the intestinalin vitrouptake of methyl-glucose in the rat. The aim of this study was to investigate the effect of dietary thylakoids on the gut microbiota composition, mainly the taxa of lactobacilli and bifidobacteria, in rats fed either a thylakoid-enriched diet or a control diet for 10 d. At the same time, a glucose-tolerance test in the same rats was also performed. Food intake was significantly decreased in the thylakoid-fed rats compared with the control-fed rats over the 10-d study. An oral glucose tolerance test after 10 d of thylakoid- or control-food intake resulted in significantly reduced plasma insulin levels in the thylakoid-fed rats compared with the control-fed rats, while no difference was observed for blood glucose levels. Analysis of gut bacteria showed a significant increase of lactobacilli on the ileal mucosa, specificallyLactobacillus reuteri, in the rats fed the thylakoid diet compared with rats fed the control diet, while faecal lactobacilli decreased. No difference in bifidobacteria between the thylakoid and control groups was found. Analyses with terminal restriction fragment length polymorphism and principal component analysis of faeces demonstrated different microbial populations in the thylakoid- and control-fed animals. These findings indicate that thylakoids modulate the gut microbial composition, which might be important for the regulation of body weight and energy metabolism.

scholarly journals High Intakes of [6S]-5-Methyltetrahydrofolic Acid Compared with Folic Acid during Pregnancy Programs Central and Peripheral Mechanisms Favouring Increased Food Intake and Body Weight of Mature Female Offspring

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1477
Author(s):  
Emanuela Pannia ◽  
Rola Hammoud ◽  
Ruslan Kubant ◽  
Jong Yup Sa ◽  
Rebecca Simonian ◽  
...  
Keyword(s):  
Body Weight ◽  
Folic Acid ◽  
Food Intake ◽  
Leptin Receptor ◽  
Liver Weight ◽  
Female Offspring ◽  
Mature Female ◽  
Cytokine Signaling ◽  
Light Cycle ◽  
Energy Regulation

Supplementation with [6S]-5-methyltetrahydrofolic acid (MTHF) is recommended as an alternative to folic acid (FA) in prenatal supplements. This study compared equimolar gestational FA and MTHF diets on energy regulation of female offspring. Wistar rats were fed an AIN-93G diet with recommended (2 mg/kg diet) or 5-fold (5X) intakes of MTHF or FA. At weaning, female offspring were fed a 45% fat diet until 19 weeks. The 5X-MTHF offspring had higher body weight (>15%), food intake (8%), light-cycle energy expenditure, and lower activity compared to 5X-FA offspring (p < 0.05). Both the 5X offspring had higher plasma levels of the anorectic hormone leptin at birth (60%) and at 19 weeks (40%), and lower liver weight and total liver lipids compared to the 1X offspring (p < 0.05). Hypothalamic mRNA expression of leptin receptor (ObRb) was lower, and of suppressor of cytokine signaling-3 (Socs3) was higher in the 5X-MTHF offspring (p < 0.05), suggesting central leptin dysregulation. In contrast, the 5X-FA offspring had higher expression of genes encoding for dopamine and GABA- neurotransmitter receptors (p < 0.01), consistent with their phenotype and reduced food intake. When fed folate diets at the requirement level, no differences were found due to form in the offspring. We conclude that MTHF compared to FA consumed at high levels in the gestational diets program central and peripheral mechanisms to favour increased weight gain in the offspring. These pre-clinical findings caution against high gestational intakes of folates of either form and encourage clinical trials examining their long-term health effects when consumed during pregnancy.

The impact of maternal protein restriction during perinatal life on the response to a septic insult in adult rats

2020 ◽  
pp. 1-8
Author(s):  
Reza Khazaee ◽  
Anastasiya Vinokurtseva ◽  
Lynda A. McCaig ◽  
Cory Yamashita ◽  
Daniel B. Hardy ◽  
...  
Keyword(s):  
Control Diet ◽  
Protein Restriction ◽  
Saline Control ◽  
Female Adult ◽  
Adult Rats ◽  
Male And Female ◽  
Maternal Protein Restriction ◽  
And Control ◽  
The Impact ◽  
Septic Insult

Abstract Although abundant evidence exists that adverse events during pregnancy lead to chronic conditions, there is limited information on the impact of acute insults such as sepsis. This study tested the hypothesis that impaired fetal development leads to altered organ responses to a septic insult in both male and female adult offspring. Fetal growth restricted (FGR) rats were generated using a maternal protein-restricted diet. Male and female FGR and control diet rats were housed until 150–160 d of age when they were exposed either a saline (control) or a fecal slurry intraperitoneal (Sepsis) injection. After 6 h, livers and lungs were analyzed for inflammation and, additionally, the amounts and function of pulmonary surfactant were measured. The results showed increases in the steady-state mRNA levels of inflammatory cytokines in the liver in response to the septic insult in both males and females; these responses were not different between FGR and control diet groups. In the lungs, cytokines were not detectable in any of the experimental groups. A significant decrease in the relative amount of surfactant was observed in male FGR offspring, but this was not observed in control males or in female animals. Overall, it is concluded that FGR induced by maternal protein restriction does not impact liver and lung inflammatory response to sepsis in either male or female adult rats. An altered septic response in male FGR offspring with respect to surfactant may imply a contribution to lung dysfunction.

Protein appetite is increased after central leptin-induced fat depletion

2007 ◽  
Vol 293 (4) ◽  
pp. R1468-R1473 ◽  
Author(s):  
Michael F. Wiater ◽  
Bryan D. Hudson ◽  
Yvette Virgin ◽  
Sue Ritter
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Body Fat ◽  
Caloric Intake ◽  
Sprague Dawley ◽  
Body Protein ◽  
Macronutrient Selection ◽  
Daily Diet ◽  
Nadir Point ◽  
And Control

Leptin reduces body fat selectively, sparing body protein. Accordingly, during chronic leptin administration, food intake is suppressed, and body weight is reduced until body fat is depleted. Body weight then stabilizes at this fat-depleted nadir, while food intake returns to normal caloric levels, presumably in defense of energy and nutritional homeostasis. This model of leptin treatment offers the opportunity to examine controls of food intake that are independent of leptin's actions, and provides a window for examining the nature of feeding controls in a “fatless” animal. Here we evaluate macronutrient selection during this fat-depleted phase of leptin treatment. Adult, male Sprague-Dawley rats were maintained on standard pelleted rodent chow and given daily lateral ventricular injections of leptin or vehicle solution until body weight reached the nadir point and food intake returned to normal levels. Injections were then continued for 8 days, during which rats self-selected their daily diet from separate sources of carbohydrate, protein, and fat. Macronutrient choice differed profoundly in leptin and control rats. Leptin rats exhibited a dramatic increase in protein intake, whereas controls exhibited a strong carbohydrate preference. Fat intake did not differ between groups at any time during the 8-day test. Despite these dramatic differences in macronutrient selection, total daily caloric intake did not differ between groups except on day 2. Thus controls of food intake related to ongoing metabolic and nutritional requirements may supersede the negative feedback signals related to body fat stores.

scholarly journals Effect of chronic infusion of olanzapine and clozapine on food intake and body weight gain in male and female rats

Life Sciences ◽  
2007 ◽  
Vol 81 (12) ◽  
pp. 1024-1030 ◽  
Author(s):  
SuJean Choi ◽  
Briana DiSilvio ◽  
JayLynn Unangst ◽  
John D. Fernstrom
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Food Intake ◽  
Body Weight Gain ◽  
Female Rats ◽  
Male And Female ◽  
Male And Female Rats ◽  
Chronic Infusion

scholarly journals Effects of withdrawal of copper sulphate from the diet of the mature domestic fowl with special reference to production and tissue mineral content

1980 ◽  
Vol 43 (3) ◽  
pp. 551-559 ◽  
Author(s):  
Mary H Stevenson ◽  
N. Jackson
Keyword(s):  
Body Weight ◽  
Bile Duct ◽  
Food Intake ◽  
Adverse Effects ◽  
Domestic Fowl ◽  
Egg Production ◽  
Mineral Content ◽  
Control Diet ◽  
Iron Concentration ◽  
Blood Haemoglobin

1. Cereal-based diets containing 0, 500, 1000 or 2000 mg added copper/kg were offered ad lib. to laying hens for 8 weeks. All the hens were subsequently offered the control diet (no added Cu, 7.5 mg Cu/kg).2. Hens from each treatment were killed at 0, 2, 4, 6 and 8 weeks after removal of the Cu-supplemented diets. Records were kept of body-weight, food consumption and egg production.3. After slaughter, blood haemoglobin, packed cell volume, serum Cu and aspartate aminotransferase (AAT; EC 2.6.1.1) were assayed. The liver, kidneys, oviduct, ovary, gizzard, caeca and bile duct were weighed.4. Mean Cu, zinc and iron concentration of liver, kidneys and caecal contents were determined.5. The adverse effects of Cu on body-weight, food intake, egg production and liver, oviduct, ovary, gizzard and bile weights were rapidly reversed by removal of added Cu from the diets.6. Greatly enhanced liver Cu concentration resulted from feeding the high-Cu diets but this effect was rapidly reversed on removal of added Cu from the diets. Liver Fe concentration showed a less marked but similar effect.7. The Cu concentration of caecal contents was increased by Cu supplementation and rapidly reduced after withdrawal of the Cu-containing diets.

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