scholarly journals Photoperiodic Regulation of Leptin Sensitivity in the Siberian Hamster, Phodopus sungorus, Is Reflected in Arcuate Nucleus SOCS-3 (Suppressor of Cytokine Signaling) Gene Expression

Endocrinology ◽  
2004 ◽  
Vol 145 (3) ◽  
pp. 1185-1193 ◽  
Author(s):  
Alexander Tups ◽  
Claire Ellis ◽  
Kim M. Moar ◽  
Tracy J. Logie ◽  
Clare L. Adam ◽  
...  
Keyword(s):  
Gene Expression ◽  
Body Weight ◽  
Arcuate Nucleus ◽  
Janus Kinase ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
Serum Leptin ◽  
Siberian Hamster ◽  
Leptin Sensitivity ◽  
Socs3 Mrna

Abstract We present the first evidence that suppressor of cytokine signaling-3 (SOCS3), a protein inhibiting Janus kinase/signal transducer and activator of transcription (STAT) signaling distal of the leptin receptor, conveys seasonal changes in leptin sensitivity in the Siberian hamster. Food deprivation (48 h) reduced SOCS3 gene expression in hamsters acclimated to either long (LD) or short (SD) photoperiods, suggesting that leptin signals acute starvation regardless of photoperiod. However, SOCS3 mRNA levels were substantially lower in the hypothalamic arcuate nucleus of hamsters acclimated to SD than in those raised in LD. In juveniles raised in LD, a rapid increase in SOCS3 mRNA was observed within 4 d of weaning, which was completely prevented by transfer to SD on the day of weaning. The early increase in SOCS3 gene expression in juvenile hamsters in LD clearly preceded the establishment of different body weight trajectories in LD and SD. In adult LD hamsters, SOCS3 mRNA was maintained at an elevated level despite the chronic food restriction imposed to lower body weight and serum leptin to or even below SD levels. A single injection of leptin in SD hamsters elevated SOCS3 mRNA to LD levels, whereas leptin treatment had no effect on SOCS3 gene expression in LD hamsters. Our results suggest that the development of leptin resistance in LD-acclimated hamsters involves SOCS3-mediated suppression of leptin signaling in the arcuate nucleus. Increased SOCS3 expression in LD hamsters is independent of body fat and serum leptin levels, suggesting that the photoperiod is able to trigger the biannual reversible switch in leptin sensitivity.

scholarly journals Enhanced leptin sensitivity and improved glucose homeostasis in mice lacking suppressor of cytokine signaling-3 in POMC-expressing cells

2006 ◽  
Vol 4 (2) ◽  
pp. 123-132 ◽  
Author(s):  
Paul Kievit ◽  
Jane K. Howard ◽  
Michael K. Badman ◽  
Nina Balthasar ◽  
Roberto Coppari ◽  
...  
Keyword(s):  
Glucose Homeostasis ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
Leptin Sensitivity

scholarly journals A Role of Suppressor of Cytokine Signaling 3 (SOCS3/CIS3/SSI3) in CD28-mediated Interleukin 2 Production

2003 ◽  
Vol 197 (4) ◽  
pp. 425-436 ◽  
Author(s):  
Akira Matsumoto ◽  
Yoh-ichi Seki ◽  
Ryosuke Watanabe ◽  
Katsuhiko Hayashi ◽  
James A. Johnston ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Interleukin 2 ◽  
Sh2 Domain ◽  
Janus Kinase ◽  
Expression Level ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
Cd28 Costimulation

Suppressor of cytokine signaling (SOCS)3 has been characterized as a negative feedback regulator in cytokine-mediated Janus kinase signal transducer and activator of transcription signaling. However, this study shows that T cells from transgenic mice expressing SOCS3 exhibit a significant reduction in interleukin (IL)-2 production induced by T cell receptor cross-linking when T cells are costimulated with CD28. Decreased protein expression in SOCS3+/− mice enhanced CD28-mediated IL-2 production, clearly indicating the correlation between expression level of SOCS3 and IL-2 production ability. The SOCS3 protein interacted with phosphorylated CD28 through its SH2 domain but not the kinase inhibitory region. In addition, a point mutation in the SOCS3 SH2 domain attenuated the inhibition of CD28 function in IL-2 promoter activation. Committed T helper (Th)2 cells exclusively expressed SOCS3 and production of Th2 cytokines, such as IL-4 and IL-5, was much less dependent on CD28 costimulation compared with interferon γ and IL-2 production in Th1 cells. Consistent with this notion, the expression level of SOCS3 in early T cell activation influenced the ability of IL-2 production induced by CD28 costimulation. Therefore, the SOCS3 may play an alternative role in prohibiting excessive progression of CD28-mediated IL-2 production.

scholarly journals Regulation and role of suppressor of cytokine signaling-3 in hypothalamic 4B cells

2009 ◽  
Vol 201 (3) ◽  
pp. 369-376 ◽  
Author(s):  
Kazunori Kageyama ◽  
Komaki Hanada ◽  
Yasumasa Iwasaki ◽  
Toshihiro Suda
Keyword(s):  
Gene Expression ◽  
Stress Responses ◽  
Negative Regulator ◽  
Cytokine Signaling ◽  
Mrna Levels ◽  
Suppressor Of Cytokine Signaling ◽  
Hypothalamic Cells ◽  
Parvocellular Neurons ◽  
Response To Stress ◽  
Inhibitory Signaling

Corticotropin-releasing factor (CRF) plays a central role in regulating stress responses. In the hypothalamic paraventricular nucleus (PVN), CRF, produced in response to stress, stimulates the release of ACTH from the anterior pituitary. ACTH then stimulates the release of glucocorticoids from the adrenal glands; circulating glucocorticoids are critical for recovery from stress conditions. Cytokines are also implicated in the regulation of CRF expression. Among them, interleukin (IL)-6 plays a role in the regulation of CRF. Factors other than glucocorticoids are likely to be involved in limiting the stimulation of CRF during stress. Suppressor of cytokine signaling (SOCS)-3 acts as a potent negative regulator of cytokine signaling. Little is known about the ability of the inhibitory signaling pathways to limit activation of the CRF gene in parvocellular PVN neurons. Hypothalamic 4B cells are useful for exploring the mechanisms, because these cells show characteristics of the parvocellular neurons of the PVN. In the present study, we examined whether SOCS-3 is regulated by IL-6 and cAMP in hypothalamic 4B cells. We also explored the involvement of SOCS-3 in the regulation of CRF gene expression. SOCS-3 was found to be regulated by IL-6 and via the cAMP/protein kinase A pathway in the hypothalamic cells. SOCS-3 knockdown increased IL-6- or forskolin-induced CRF gene transcription and mRNA levels. Therefore, SOCS-3, induced by a cAMP stimulant and IL-6, would be involved in the negative regulation of CRF gene expression in hypothalamic cells.

Suppressor of cytokine signaling 2 (SOCS2) deletion protects against multiple low dose streptozotocin-induced type 1 diabetes in adult male mice

2016 ◽  
Vol 26 (1) ◽  
Author(s):  
Amira Alkharusi ◽  
Mercedes Mirecki-Garrido ◽  
Zuheng Ma ◽  
Fahad Zadjali ◽  
Amilcar Flores-Morales ◽  
...  
Keyword(s):  
Type I Diabetes ◽  
Janus Kinase ◽  
Cytokine Signaling ◽  
Type I ◽  
Suppressor Of Cytokine Signaling ◽  
Β Cell ◽  
Diabetes In Mice ◽  
Socs Proteins ◽  
Stat Pathway

AbstractDiabetes type 1 is characterized by the failure of beta cells to produce insulin. Suppressor of cytokine signaling (SOCS) proteins are important regulators of the Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway. Previous studies have shown that GH can prevent the development of type I diabetes in mice and that SOCS2 deficiency mimics a state of increased GH sensitivity.The elevated sensitivity of SOCS2We show that 6-month-old SOCS2Knockdown of SOCS2 makes mice less sensitive to MLDSTZ. These results are consistent with the proposal that elimination of SOCS2 in pancreatic islets creates a state of β-cell hypersensitivity to GH/PRL that mimics events in pregnancy, and which is protective against MLDSTZ-induced type I diabetes in mice. SOCS2-dependent control of β-cell survival may be of relevance to islet regeneration and survival in transplantation.

scholarly journals Anti-inflammatory, antioxidant and renoprotective effects of SOCS1 mimetic peptide in the BTBR ob/ob mouse model of type 2 diabetes

2020 ◽  
Vol 8 (1) ◽  
pp. e001242 ◽  
Author(s):  
Lucas Opazo-Ríos ◽  
Yenniffer Sanchez Matus ◽  
Raúl R Rodrigues-Díez ◽  
Daniel Carpio ◽  
Alejandra Droguett ◽  
...  
Keyword(s):  
Gene Expression ◽  
Type 2 Diabetes ◽  
Kidney Disease ◽  
Mouse Model ◽  
Janus Kinase ◽  
Cytokine Signaling ◽  
Mimetic Peptide ◽  
Active Peptide ◽  
Socs Proteins

IntroductionDiabetic nephropathy (DN) is the leading cause of chronic kidney disease worldwide. The Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway participates in the development and progression of DN. Among the different mechanisms involved in JAK/STAT negative regulation, the family of suppressor of cytokine signaling (SOCS) proteins has been proposed as a new target for DN. Our aim was to evaluate the effect of SOCS1 mimetic peptide in a mouse model of obesity and type 2 diabetes (T2D) with progressive DN.Research design and methodsSix-week-old BTBR (black and tan brachyuric) mice with the ob/ob (obese/obese) leptin-deficiency mutation were treated for 7 weeks with two different doses of active SOCS1 peptide (MiS1 2 and 4 µg/g body weight), using inactive mutant peptide (Mut 4 µg) and vehicle as control groups. At the end of the study, the animals were sacrificed to obtain blood, urine and kidney tissue for further analysis.ResultsTreatment of diabetic mice with active peptide significantly decreased urine albumin to creatinine ratio by up to 50%, reduced renal weight, glomerular and tubulointerstitial damage, and restored podocyte numbers. Kidneys from treated mice exhibited lower inflammatory infiltrate, proinflammatory gene expression and STAT activation. Concomitantly, active peptide administration modulated redox balance markers and reduced lipid peroxidation and cholesterol transporter gene expression in diabetic kidneys.ConclusionTargeting SOCS proteins by mimetic peptides to control JAK/STAT signaling pathway ameliorates albuminuria, morphological renal lesions, inflammation, oxidative stress and lipotoxicity, and could be a therapeutic approach to T2D kidney disease.

Endothelin-1 stimulates suppressor of cytokine signaling-3 gene expression in adipocytes

2012 ◽  
Vol 178 (3) ◽  
pp. 450-458 ◽  
Author(s):  
Hsin-Huei Chang ◽  
Yao-Ming Huang ◽  
Chi-Peng Wu ◽  
Ya-Chu Tang ◽  
Chi-Wei Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
Endothelin 1

scholarly journals Seasonal effects of central leptin infusion on secretion of melatonin and prolactin and on SOCS-3 gene expression in ewes

2008 ◽  
Vol 198 (1) ◽  
pp. 147-155 ◽  
Author(s):  
D A Zieba ◽  
M Szczesna ◽  
B Klocek-Gorka ◽  
E Molik ◽  
T Misztal ◽  
...  
Keyword(s):  
Third Ventricle ◽  
Plasma Concentrations ◽  
Seasonal Effects ◽  
Cytokine Signaling ◽  
Dependent Manner ◽  
Suppressor Of Cytokine Signaling ◽  
Medial Basal Hypothalamus ◽  
Leptin Sensitivity ◽  
Dose Dependent ◽  
Short Days

Recent studies have demonstrated photoperiodic changes in leptin sensitivity of seasonal mammals. Herein, we examined the interaction of season (long days (LD) versus short days (SD)) and recombinant ovine leptin (roleptin) on secretion of melatonin and prolactin (PRL) and on mRNA expression of suppressor of cytokine signaling-3 (SOCS-3) in the medial basal hypothalamus (MBH) in sheep. Twenty-four Polish Longwool ewes, surgically fitted with third ventricle (IIIV) cannulas, were utilized in a replicated switchback design involving 12 ewes per season. Within-season and replicate ewes were assigned randomly to one of three treatments (four ewes/treatment) and infused centrally three times at 0, 1 and 2 h beginning at sunset. Treatments were 1) control, Ringer–Locke buffer; 2) L1, roleptin, 0.5 μg/kg BW; and 3) L2, roleptin, 1.0 μg/kg BW. Jugular blood samples were collected at 15-min intervals beginning immediately before the start of infusions and continued for 6 h. At the end of blood sampling, a washout period of at least 3 days elapsed before ewes were re-randomized and treated with one of the treatments described above (four ewes/treatment). Ewes were then killed and brains were collected for MBH processing. Leptin treatments increased (P<0.001) circulating leptin concentrations compared with controls during both seasons in a dose-dependent manner. Overall, mean plasma concentrations of melatonin were greater (P<0.001) during LD than SD. However, leptin treatments increased melatonin concentrations during SD in a dose-dependent manner and decreased it during LD. Similarly, plasma concentrations of PRL were greater (P<0.001) during LD than SD. However, unlike changes in melatonin, circulating PRL decreased (P<0.001) in response to leptin during LD. Semi-quantitative PCR revealed that leptin increased (P<0.001) SOCS-3 expression in the MBH region during LD in a dose-dependent manner. Data provide evidence that secretion of photoperiodic hormones such as melatonin and PRL are inversely regulated by leptin during SD and LD. However, the increase in expression of SOCS-3 in the MBH during LD compared with SD fails to fully explain these effects.

scholarly journals Suppressor of Cytokine Signaling 3 Is Induced by Angiotensin II in Heart and Isolated Cardiomyocytes, and Participates in Desensitization

Endocrinology ◽  
2003 ◽  
Vol 144 (10) ◽  
pp. 4586-4596 ◽  
Author(s):  
Vivian C. Calegari ◽  
Rosangela M. N. Bezerra ◽  
Márcio A. Torsoni ◽  
Adriana S. Torsoni ◽  
Kleber G. Franchini ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Rat Heart ◽  
Ventricular Myocytes ◽  
Janus Kinase ◽  
Neonatal Rat ◽  
Cytokine Signaling ◽  
Ang Ii ◽  
Suppressor Of Cytokine Signaling ◽  
Rat Ventricular Myocytes ◽  
Neonatal Rat Ventricular Myocytes

Angiotensin II (Ang II) exerts a potent growth stimulus on the heart and vascular wall. Activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) intracellular signaling pathway by Ang II mediates at least some of the mitogenic responses to this hormone. In other signaling systems that use the JAK/STAT pathway, proteins of the suppressor of cytokine signaling (SOCS) family participate in signal regulation. In the present study it is demonstrated that SOCS3 is constitutively expressed at a low level in rat heart and neonatal rat ventricular myocytes. Ang II at a physiological concentration enhances the expression of SOCS3 mRNA and protein, mainly via AT1 receptors. After induction, SOCS3 associates with JAK2 and impairs further activation of the JAK2/STAT1 pathway. Pretreatment of rats with a specific phosphorthioate antisense oligonucleotide to SOCS3, reverses the desensitization to angiotensin signaling, as detected by a fall in c-Jun expression after repetitive infusions of the hormone. Thus, SOCS3 is induced by Ang II in rat heart and neonatal rat ventricular myocytes and participates in the modulation of the signal generated by this hormone.

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