Protein tyrosine phosphatase 1B negatively regulates leptin signaling in a hypothalamic cell line

Kaszubska, Wiweka; Falls, Hugh D.; Schaefer, Verlyn G.; Haasch, Deanna L.; Frost, Leigh; Hessler, Paul; Kroeger, Paul E.; White, David W.; Jirousek, Michael R.; Trevillyan, James M.

doi:10.1016/s0303-7207(02)00178-8

Cited by 163 publications

(109 citation statements)

References 36 publications

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“…PTP1B antagonizes the action of the adipocyte-secreted hormone leptin by directly dephosphorylating the leptin receptorassociated Janus kinase 2 (5)(6)(7)(8). Leptin acts within the brain to regulate energy homeostasis by suppressing food intake and elevating energy expenditure, and the metabolic effects of central PTP1B deficiency have been attributed to improved leptin sensitivity (9 -13).…”

mentioning

confidence: 99%

Protein-tyrosine Phosphatase 1B (PTP1B) Is a Novel Regulator of Central Brain-derived Neurotrophic Factor and Tropomyosin Receptor Kinase B (TrkB) Signaling

Ozek

Kanoski

Zhang

et al. 2014

Journal of Biological Chemistry

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Background:The tropomyosin receptor kinase B (TrkB) is a potential novel substrate of protein-tyrosine phosphatase 1B (PTP1B). Results: PTP1B associates with and plays a modulatory role in BDNF-induced TrkB signaling. Conclusion: PTP1B is a novel negative regulator of central BDNF/TrkB signaling. Significance: This is the first evidence that PTP1B deficiency enhances central TrkB signaling and alters BDNF-induced thermogenesis in vivo.

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mentioning

confidence: 99%

Protein-tyrosine Phosphatase 1B (PTP1B) Is a Novel Regulator of Central Brain-derived Neurotrophic Factor and Tropomyosin Receptor Kinase B (TrkB) Signaling

Ozek

Kanoski

Zhang

et al. 2014

Journal of Biological Chemistry

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“…Likewise, several research groups have investigated blocking those negative regulators of leptin signalling such as SOCS3 and the phosphor-tyrosine protein phosphatase PTP 1B to improve the leptin response in obese persons (Kaszubska et al, 2002;Reed et al, 2010;Roujeau et al, 2014). Furthermore, co-administration of leptin with either exendin-4 or FGF21 has been shown to restore leptin responsiveness in diet-induced obese mice (Kim et al, 2006;Müller et al;.…”

Section: Multi-therapy Of Leptinmentioning

confidence: 99%

Critically Discuss the Revival of Leptin for Obesity Therapy

Lo¹

2018

PSYCH

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Obesity has created a very serious public health problem, and World Health Organisation has actually warned that there is an urgent need for multinational cooperation to stem the rise of obesity. More than 20 years ago the discovery of Leptin, which is an adipocyte-secreted hormone and primarily acts on the hypothalamic neurons to activate the regulation of energy homeostasis, created much interest in its potential use for the treatment of obesity, but the hope was soon lost after leptin failed to counteract common diet-induced obesity. In recent years some preclinical studies have surprisingly demonstrated that resistance to leptin can be reversed and the effects of leptin therapy can be amplified by several leptin sensitisers. This paper will critically discuss the plausible revival of leptin for obesity therapy with reference to research findings on various influencing factors contributing to the level of expression and secretion of leptin.

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“…Interaction of Sos with Ras activates a serine signalling cascade whereby Ras-Raf-MEK and mitogen-activated protein kinase (MAPK) are activated, as part of the ERK signalling cascade [14,15]. In addition cytokine signalling inhibitors, including cytokine inducible sequence (CIS), suppressor of cytokine signalling (SOCS3) and protein tyrosine phosphatase 1B (PTP1B), inhibit leptin signalling by binding to phosphorylated JAK2 [16,17].…”

Section: Leptin Receptor Signallingmentioning

confidence: 99%

Leptin Regulation of Synaptic Function at Hippocampal TA-CA1 and SC-CA1 Synapses: Implications for Health and Disease

McGregor

Harvey

2017

Neurochem Res

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Discovery of the obese (ob) gene in 1994 via positional cloning techniques enabled insight into the physiological system that controls body weight and energy expenditure [1]. Subsequent investigations identified the ob gene product as a 16 kDa protein that reduced food intake and increased energy expenditure in genetically obese (ob/ob) rodent models, indicating a pivotal role in regulating energy homeostasis. This protein was termed leptin [2,3].Leptin is primarily produced and secreted by white adipose tissue and circulates in proportion to adipose mass [3]. The leptin receptor (Ob-R) is encoded by the diabetes (db) gene [4]. Leptin gains access to the hypothalamus to regulate energy homeostasis via a saturable transport mechanism or by binding to receptors at the blood-brain barrier interface [5]. However recent evidence suggests that leptin can also be made locally within the CNS as leptin mRNA and protein has been detected within the brain [6].At least six different isoforms (Ob-R a-f ) of Ob-R exist (Fig. 1) as a result of alternative splicing of the db gene [7,8]. Each isoform has an identical N-terminal ligand-binding domain but a differential C-terminal region required for signalling. Each isoform gives rise to a single membranespanning receptor with the exception of Ob-R e which is thought to circulate as a soluble leptin binding protein. The remaining Ob-R isoforms have either a short intracellular domain containing 30-40 cytoplasmic residues (Ob-R a,c,d,f ) or a large intracellular domain consisting of 302 residues (known as the long form of the receptor (Ob-R b ), which is the most signalling competent form of the receptor [9].Abstract Growing evidence indicates that the endocrine hormone leptin regulates hippocampal synaptic function in addition to its established role as a hypothalamic satiety signal. Indeed, numerous studies show that leptin facilitates the cellular events that underlie hippocampal learning and memory including activity-dependent synaptic plasticity and glutamate receptor trafficking, indicating that leptin may be a potential cognitive enhancer. Although there has been extensive investigation into the modulatory role of leptin at hippocampal Schaffer collateral (SC)-CA1 synapses, recent evidence indicates that leptin also potently regulates excitatory synaptic transmission at the anatomically distinct temporoammonic (TA) input to hippocampal CA1 neurons. The cellular mechanisms underlying activity-dependent synaptic plasticity at TA-CA1 synapses differ from those at SC-CA1 synapses and the TA input is implicated in spatial and episodic memory formation. Furthermore, the TA input is an early target for neurodegeneration in Alzheimer's disease (AD) and aberrant leptin function is linked to AD. Here, we review the evidence that leptin regulates hippocampal synaptic function at both SC-and TA-CA1 synapses and discuss the consequences for neurodegenerative disorders like AD.

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Protein tyrosine phosphatase 1B negatively regulates leptin signaling in a hypothalamic cell line

Cited by 163 publications

References 36 publications

Protein-tyrosine Phosphatase 1B (PTP1B) Is a Novel Regulator of Central Brain-derived Neurotrophic Factor and Tropomyosin Receptor Kinase B (TrkB) Signaling

Protein-tyrosine Phosphatase 1B (PTP1B) Is a Novel Regulator of Central Brain-derived Neurotrophic Factor and Tropomyosin Receptor Kinase B (TrkB) Signaling

Critically Discuss the Revival of Leptin for Obesity Therapy

Leptin Regulation of Synaptic Function at Hippocampal TA-CA1 and SC-CA1 Synapses: Implications for Health and Disease

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