scholarly journals Changes in Expression of the Genes for the Leptin Signaling in Hypothalamic-Pituitary Selected Areas and Endocrine Responses to Long-Term Manipulation in Body Weight and Resistin in Ewes

2020 ◽  
Vol 21 (12) ◽  
pp. 4238
Author(s):  
Dorota Anna Zieba ◽  
Weronika Biernat ◽  
Malgorzata Szczesna ◽  
Katarzyna Kirsz ◽  
Justyna Barć ◽  
...  
Keyword(s):  
Body Weight ◽  
Leptin Receptor ◽  
Fat Body ◽  
Density Lipoprotein ◽  
Reproductive Hormones ◽  
Leptin Resistance ◽  
Nonesterified Fatty Acid ◽  
Cytokine Signaling ◽  
Leptin Signaling

Both long-term undernutrition and overnutrition disturb metabolic balance, which is mediated partially by the action of two adipokines, leptin and resistin (RSTN). In this study, we manipulated the diet of ewes to produce either a thin (lean) or fat (fat) body condition and investigated how RSTN affects endocrine and metabolic status under different leptin concentrations. Twenty ewes were distributed into four groups (n = 5): the lean and fat groups were administered with saline (Lean and Fat), while the Lean-R (Lean-Resistin treated) and Fat-R (Fat-Resistin treated) groups received recombinant bovine resistin. Plasma was assayed for LH, FSH, PRL, RSTN, leptin, GH, glucose, insulin, total cholesterol, nonesterified fatty acid (NEFA), high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol and triglycerides. Expression levels of a suppressor of cytokine signaling (SOCS-3) and the long form of the leptin receptor (LRb) were determined in selected brain regions, such as the anterior pituitary, hypothalamic arcuate nucleus, preoptic area and ventro- and dorsomedial nuclei. The results indicate long-term alterations in body weight affect RSTN-mediated effects on metabolic and reproductive hormones concentrations and the expression of leptin signaling components: LRb and SOCS-3. This may be an adaptive mechanism to long-term changes in adiposity during the state of long-day leptin resistance.

Crosstalk between leptin and interleukin-1β abrogates negative inotropic effects in a model of chronic hyperleptinemia

2011 ◽  
Vol 236 (11) ◽  
pp. 1263-1273 ◽  
Author(s):  
M Judith Radin ◽  
Bethany J Holycross ◽  
Sylvia A McCune ◽  
Ruth A Altschuld
Keyword(s):  
Heart Failure ◽  
Cardiac Myocytes ◽  
Leptin Receptor ◽  
Interleukin 1 ◽  
Negative Inotropic Effect ◽  
Leptin Resistance ◽  
Cytokine Signaling ◽  
Inotropic Effects ◽  
Negative Inotropic Effects

Interleukin 1 beta (IL-1 β) is a proinflammatory cytokine with potent cardiosuppressive effects. Previous studies have shown that leptin blunts the negative inotropic effects of IL-1 β in isolated adult rat cardiac myocytes. However, the interactions between leptin and IL-1 β in the heart have not been examined on a background of chronic hyperleptinemia. To study this interaction, we have chosen the SHHF rat, a model of spontaneous hypertension that ultimately develops congestive heart failure. SHHF that are heterozygous for a null mutation of the leptin receptor (+/ fa cp, HET) are phenotypically lean but chronically hyperleptinemic and develop heart failure earlier than their normoleptinemic true lean (+/+, LN) littermates. Simultaneous cell shortening and calcium transients were measured in isolated ventricular cardiac myocytes from LN and HET SHHF in response to leptin, IL-1 β or IL-1 β following one hour pretreatment with leptin. Despite evidence of metabolic leptin resistance, HET myocytes were sensitive to the negative inotropic effect of leptin, similar to LN. Contractility returned to control levels in myocytes from HET that were pretreated with leptin prior to IL-1 β, while contractility remained depressed compared with control and similar to leptin alone in LN. Chronic hyperleptinemia resulted in altered JAK/STAT signaling in response to leptin and IL-1 β in isolated perfused hearts from HET compared with LN SHHF. Phosphorylated STAT3 (pSTAT3) and STAT5 (pSTAT5) decreased when HET hearts were treated with leptin followed by IL-1 β. While decreases in pSTAT3 and pSTAT5 may be associated with abrogation of the acute negative inotropic effects of IL-1 β in the presence of leptin in HET, long-term consequences remain to be explored. This study demonstrates that the heart remains sensitive to leptin in a hyperleptinemic state. Crosstalk between leptin and IL-1 β can influence cardiac function and cytokine signaling and these interactions are moderated by the presence of long-term hyperleptinemia.

scholarly journals Leptin Signaling in the Hypothalamus during Chronic Central Leptin Infusion

Endocrinology ◽  
2003 ◽  
Vol 144 (9) ◽  
pp. 3789-3798 ◽  
Author(s):  
Rekha Pal ◽  
Abhiram Sahu
Keyword(s):  
Food Intake ◽  
Leptin Receptor ◽  
Binding Activity ◽  
Janus Kinase ◽  
Male Rats ◽  
Leptin Resistance ◽  
Cytokine Signaling ◽  
Mrna Levels ◽  
Leptin Signaling ◽  
Initial Decrease

Abstract Using a rat model of chronic central leptin infusion in which neuropeptide Y neurons develop leptin resistance, we examined whether leptin signal transduction mechanism in the hypothalamus is altered during central leptin infusion. Adult male rats were infused chronically into the lateral cerebroventricle with leptin (160 ng/h) or vehicle via Alzet pumps for 16 d. In the leptin-infused group, the initial decrease in food intake was followed by a recovery to their preleptin levels by d 16, although food intake remained significantly lower than in artificial cerebrospinal fluid controls; and body weight gradually decreased reaching a nadir at d 11 and remained stabilized at lower level thereafter. Phosphorylated leptin receptor and phosphorylated signal transducer and activator of transcription-3 (p-STAT3) remained elevated in association with a sustained elevation in DNA-binding activity of STAT3 in the hypothalamus throughout 16-d period of leptin infusion. However, phosphorylated Janus kinase-2 was increased during the early part of leptin infusion but remained unaltered on d 16. Although hypothalamic suppressors of cytokine signaling-3 (SOCS3) mRNA levels were increased throughout leptin infusion, SOCS3 protein levels were increased only on d 16. This study demonstrates a sustained elevation in hypothalamic leptin receptor signaling through Janus kinase-STAT pathway despite an increased expression of SOCS3 during chronic central leptin infusion. We propose that an alteration in leptin signaling in the hypothalamus through pathways other than STAT3 and/or a defect in downstream of STAT3 signaling may be involved in food intake recovery seen after an initial decrease during chronic central leptin infusion.

scholarly journals Recent advances in understanding leptin signaling and leptin resistance

2009 ◽  
Vol 297 (6) ◽  
pp. E1247-E1259 ◽  
Author(s):  
David L. Morris ◽  
Liangyou Rui
Keyword(s):  
Endoplasmic Reticulum ◽  
Body Weight ◽  
Risk Factor ◽  
Energy Homeostasis ◽  
Leptin Receptor ◽  
Leptin Resistance ◽  
Leptin Signaling ◽  
Long Form ◽  
The Brain ◽  
Primary Risk Factor

The brain controls energy homeostasis and body weight by integrating various metabolic signals. Leptin, an adipose-derived hormone, conveys critical information about peripheral energy storage and availability to the brain. Leptin decreases body weight by both suppressing appetite and promoting energy expenditure. Leptin directly targets hypothalamic neurons, including AgRP and POMC neurons. These leptin-responsive neurons widely connect to other neurons in the brain, forming a sophisticated neurocircuitry that controls energy intake and expenditure. The anorexigenic actions of leptin are mediated by LEPRb, the long form of the leptin receptor, in the hypothalamus. LEPRb activates both JAK2-dependent and -independent pathways, including the STAT3, PI 3-kinase, MAPK, AMPK, and mTOR pathways. These pathways act coordinately to form a network that fully mediates leptin response. LEPRb signaling is regulated by both positive (e.g., SH2B1) and negative (e.g., SOCS3 and PTP1B) regulators and by endoplasmic reticulum stress. Leptin resistance, a primary risk factor for obesity, likely results from impairment in leptin transport, LEPRb signaling, and/or the neurocircuitry of energy balance.

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.

scholarly journals Endospanin 1 Determines the Balance of Leptin-Regulated Hypothalamic Functions

2018 ◽  
Vol 108 (2) ◽  
pp. 132-141
Author(s):  
Clara Roujeau ◽  
Ralf Jockers ◽  
Julie Dam
Keyword(s):  
Signaling Pathways ◽  
Intracellular Trafficking ◽  
Leptin Receptor ◽  
Leptin Resistance ◽  
Human Obesity ◽  
Leptin Signaling ◽  
Diet Induced Obesity ◽  
Important Regulator ◽  
Neuronal Plasma Membrane ◽  
Underlying Mechanisms

Endospanin 1 (Endo1), a protein encoded in humans by the same gene than the leptin receptor (ObR), and increased by diet-induced obesity, is an important regulator of ObR trafficking and cell surface exposure, determining leptin signaling strength. Defective intracellular trafficking of the leptin receptor to the neuronal plasma membrane has been proposed as a mechanism underlying the development of leptin resistance observed in human obesity. More recently, Endo1 has emerged as a mediator of “selective leptin resistance.” The underlying mechanisms of the latter are not completely understood, but the possibility of differential activation of leptin signaling pathways was suggested among others. In this respect, the expression level of Endo1 is crucial for the appropriate balance between different leptin signaling pathways and leptin functions in the hypothalamus and is likely participating in selective leptin resistance for the control of energy and glucose homeostasis.

scholarly journals Endothelial leptin receptor mutation provides partial resistance to diet-induced obesity

2012 ◽  
Vol 112 (8) ◽  
pp. 1410-1418 ◽  
Author(s):  
Weihong Pan ◽  
Hung Hsuchou ◽  
Germaine G. Cornelissen-Guillaume ◽  
Bhavvani Jayaram ◽  
Yuping Wang ◽  
...  
Keyword(s):  
Body Weight ◽  
Partial Resistance ◽  
Heat Dissipation ◽  
Leptin Receptor ◽  
Wild Type ◽  
Blood Concentrations ◽  
Leptin Signaling ◽  
Metabolic Chamber ◽  
Diet Induced Obesity ◽  
Obesity And Diabetes

Leptin, a polypeptide hormone produced mainly by adipocytes, has diverse effects in both the brain and peripheral organs, including suppression of feeding. Other than mediating leptin transport across the blood-brain barrier, the role of the endothelial leptin receptor remains unclear. We recently generated a mutant mouse strain lacking endothelial leptin receptor signaling, and showed that there is an increased uptake of leptin by brain parenchyma after its delivery by in situ brain perfusion. Here, we tested the hypothesis that endothelial leptin receptor mutation confers partial resistance to diet-induced obesity. These ELKO mice had similar body weight and percent fat as their wild-type littermates when fed with rodent chow, but blood concentrations of leptin were significantly elevated. In response to a high-fat diet, wild-type mice had a greater gain of body weight and fat than ELKO mice. As shown by metabolic chamber measurement, the ELKO mice had higher oxygen consumption, carbon dioxide production, and heat dissipation, although food intake was similar to that of the wild-type mice and locomotor activity was even reduced. This indicates that the partial resistance to diet-induced obesity was mediated by higher metabolic activity in the ELKO mice. Since neuronal leptin receptor knockout mice show obesity and diabetes, the results suggest that endothelial leptin signaling shows opposite effects from that of neuronal leptin signaling, with a facilitatory role in diet-induced obesity.

scholarly journals Astrocytic leptin-receptor knockout mice show partial rescue of leptin resistance in diet-induced obesity

2013 ◽  
Vol 114 (6) ◽  
pp. 734-741 ◽  
Author(s):  
Bhavaani Jayaram ◽  
Weihong Pan ◽  
Yuping Wang ◽  
Hung Hsuchou ◽  
Aurelien Mace ◽  
...  
Keyword(s):  
Heat Dissipation ◽  
Leptin Receptor ◽  
Uncoupling Protein ◽  
Subcutaneous Fat ◽  
Leptin Resistance ◽  
Blood Concentrations ◽  
Leptin Signaling ◽  
Diet Induced Obesity ◽  
Soluble Leptin Receptor ◽  
Similar Body

To determine how astrocytic leptin signaling regulates the physiological response of mice to diet-induced obesity (DIO), we performed metabolic analyses and hypothalamic leptin signaling assays on astrocytic leptin-receptor knockout (ALKO) mice in which astrocytes lack functional leptin receptor (ObR) signaling. ALKO mice and wild-type (WT) littermate controls were studied at different stages of DIO with measurement of body wt, percent fat, metabolic activity, and biochemical parameters. When fed regular chow, the ALKO mice had similar body wt, percent fat, food intake, heat dissipation, respiratory exchange ratio, and activity as their WT littermates. There was no change in blood concentrations of triglyceride, soluble leptin receptor (sObR), mRNA for leptin and uncoupling protein 1 (UCP1) in adipose tissue, and insulin sensitivity. Unexpectedly, in response to a high-fat diet the ALKO mice had attenuated hyperleptinemia and sObR, a lower level of leptin mRNA in subcutaneous fat, and a paradoxical increase in UCP1 mRNA. Thus, ALKO mice did not show the worsening of obesity that occurs with normal WT mice and the neuronal ObR mutation that results in morbid obesity. The findings are consistent with a competing, counterregulatory model between neuronal and astrocytic leptin signaling.

scholarly journals Functional Role of Suppressor of Cytokine Signaling 3 Upregulation in Hypothalamic Leptin Resistance and Long-Term Energy Homeostasis

Diabetes ◽  
2010 ◽  
Vol 59 (4) ◽  
pp. 894-906 ◽  
Author(s):  
A. S. Reed ◽  
E. K. Unger ◽  
L. E. Olofsson ◽  
M. L. Piper ◽  
M. G. Myers ◽  
...  
Keyword(s):  
Functional Role ◽  
Energy Homeostasis ◽  
Leptin Resistance ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
Term Energy

scholarly journals Leptin Sensitivity in the Developing Rat Hypothalamus

Endocrinology ◽  
2007 ◽  
Vol 148 (12) ◽  
pp. 6073-6082 ◽  
Author(s):  
A.-S. Carlo ◽  
M. Pyrski ◽  
C. Loudes ◽  
A. Faivre-Baumann ◽  
J. Epelbaum ◽  
...  
Keyword(s):  
Food Intake ◽  
Neuropeptide Y ◽  
Leptin Receptor ◽  
Primary Cultures ◽  
Cytokine Signaling ◽  
Neuronal Cultures ◽  
Mrna Levels ◽  
Leptin Signaling ◽  
Leptin Sensitivity

In adults, the adipocyte-derived hormone, leptin, regulates food intake and body weight principally via the hypothalamic arcuate nucleus (ARC). During early postnatal development, leptin functions to promote the outgrowth of neuronal projections from the ARC, whereas a selective insensitivity to the effects of leptin on food intake appears to exist. To investigate the mechanisms underlying the inability of leptin to regulate food intake during early development, leptin signaling was analyzed both in vitro using primary cultures of rat embryonic ARC neurones and in vivo by challenging early postnatal rats with leptin. In neuronal cultures, despite the presence of key components of the leptin signaling pathway, no detectable activation of either signal transducer and activator of transcription 3 or the MAPK pathways by leptin was detected. However, leptin down-regulated mRNA levels of proopiomelanocortin and neuropeptide Y and decreased somatostatin secretion. Leptin challenge in vivo at postnatal d (P) 7, P14, P21, and P28 revealed that, in contrast to adult and P28 rats, mRNA levels of neuropeptide Y, proopiomelanocortin, agouti-related peptide and cocaine- and amphetamine-regulated transcript were largely unaffected at P7, P14, and P21. Furthermore, leptin stimulation increased the suppressor of cytokine signaling-3 mRNA levels at P14, P21, and P28 in several hypothalamic nuclei but not at P7, indicating that selective leptin insensitivity in the hypothalamus is coupled to developmental shifts in leptin receptor signaling. Thus, the present study defines the onset of leptin sensitivity in the regulation of energy homeostasis in the developing hypothalamus.

scholarly journals Preoptic leptin signaling modulates energy balance independent of body temperature regulation

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Sangho Yu ◽  
Helia Cheng ◽  
Marie François ◽  
Emily Qualls-Creekmore ◽  
Clara Huesing ◽  
...  
Keyword(s):  
Body Weight ◽  
Energy Balance ◽  
Body Temperature ◽  
Energy Expenditure ◽  
Ambient Temperature ◽  
Temperature Regulation ◽  
Leptin Receptor ◽  
Energy State ◽  
Body Temperature Regulation ◽  
Leptin Signaling

The adipokine leptin acts on the brain to regulate energy balance but specific functions in many brain areas remain poorly understood. Among these, the preoptic area (POA) is well known to regulate core body temperature by controlling brown fat thermogenesis, and we have previously shown that glutamatergic, long-form leptin receptor (Lepr)-expressing neurons in the POA are stimulated by warm ambient temperature and suppress energy expenditure and food intake. Here we further investigate the role of POA leptin signaling in body weight regulation and its relationship to body temperature regulation in mice. We show that POA Lepr signaling modulates energy expenditure in response to internal energy state, and thus contributes to body weight homeostasis. However, POA leptin signaling is not involved in ambient temperature-dependent metabolic adaptations. Our study reveals a novel cell population through which leptin regulates body weight.

Sign in / Sign up

Export Citation Format

Share Document