Evaluation of new leptin fragments on food intake and body weight of normal rats

Martins, Marta N. C.; Telles, Mônica Marques; Zemdegs, Juliane Costa Silva; Andrade, Iracema Senna de; Ribeiro, Eliane; Miranda, Antônio

doi:10.1016/j.regpep.2008.11.013

Cited by 13 publications

(10 citation statements)

References 44 publications

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“…On-going efforts in the design, development, and preclinical application of lepin-related synthetic peptide agonists and antagonists [4][5][6][7][8][9][10][12][13][14][15][16][17][18][19][20][21][22][23] indicates that the apparent failure of leptin in the clinic to satisfy the therapeutic needs of the majority of obese humans has acted as a catalyst in efforts to develop novel peptide therapeutics targeted at reducing the pandemic proportions of this disease and its associated metabolic dysfunctions. In this regard, small-molecule peptide therapeutics have the potential to overcome the limitations of recombinant leptin, since their uptake into the central nervous system (CNS) is not dependent on saturable transport across the blood-brain barrier (BBB).…”

Section: Discussionmentioning

confidence: 99%

“…Reports from our laboratory [5][6][7][8]19,23], and a growing number of other laboratories [4,[12][13][14][15][16][17]21,22,24], have consistently shown that the entire leptin molecule is not required for the expression of its biological activity. Utilizing in vitro and in vivo approaches, peripheral and intracerebroventricular (ICV) delivery systems, different physiological endpoints and animal models, these studies provide convincing evidence that synthetic peptide analogs that encompass the functional epitope of leptin contain sufficient information to influence leptin-modulated physiologies by pathways that complement, augment, or diverge from those of endogenous leptin.…”

Section: Introductionmentioning

confidence: 99%

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Myristic acid conjugation of [D-Leu-4]-OB3, a biologically active leptin-related synthetic peptide amide, significantly improves its pharmacokinetic profile and efficacy

2014

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Myristic acid conjugation of [D-Leu-4]-OB3, a biologically active leptin-related synthetic peptide amide, significantly improves its pharmacokinetic profile and efficacy

2014

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“…Studies on synthetic peptides demonstrated that the entire leptin molecule is not required for biological activity (Samson et al 1996, Grasso et al 1997, de Oliveira et al 2008, Barrett et al 2009, 2011, Martins et al 2009) and leptin fragments have been detected in human serum (Stamatiadis et al 2004). However, leptin proteolytic processing and identification of its derived active sequences in circulation have not been extensively studied.…”

Section: Discussionmentioning

confidence: 99%

Cysteine cathepsin S processes leptin, inactivating its biological activity

Oliveira

Assis²,

Paschoalin³

et al. 2012

Journal of Endocrinology

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Leptin is a 16 kDa hormone mainly produced by adipocytes that plays an important role in many biological events including the regulation of appetite and energy balance, atherosclerosis, osteogenesis, angiogenesis, the immune response, and inflammation. The search for proteolytic enzymes capable of processing leptin prompted us to investigate the action of cysteine cathepsins on human leptin degradation. In this study, we observed high cysteine peptidase expression and hydrolytic activity in white adipose tissue (WAT), which was capable of degrading leptin. Considering these results, we investigated whether recombinant human cysteine cathepsins B, K, L, and S were able to degrade human leptin. Mass spectrometry analysis revealed that among the tested enzymes, cathepsin S exhibited the highest catalytic activity on leptin. Furthermore, using a Matrigel assay, we observed that the leptin fragments generated by cathepsin S digestion did not exhibit angiogenic action on endothelial cells and were unable to inhibit food intake in Wistar rats after intracerebroventricular administration. Taken together, these results suggest that cysteine cathepsins may be putative leptin activity regulators in WAT.

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“…Todos atuam nos centros hipotalâmicos, que são os grandes responsáveis pela sensação da fome, pelo estímulo à ingestão alimentar e pelo gasto energético 29,30 .…”

Section: Fisiologia Da Oxintomodulinaunclassified

Oxintomodulina e obesidade

2009

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Desde o descobrimento da leptina, avanços consideráveis foram obtidos na caracterização dos mecanismos hipotalâmicos do controle da ingestão alimentar e, atualmente, a oxintomodulina é reconhecida como um regulador da homeostase energética. O presente artigo de revisão enfoca algumas das mais relevantes inter--relações do hormônio oxintomodulina com o apetite, a homeostase energética e aspectos de seu papel na bioquímica e fisiologia nutricional. A oxintomodulina é um peptídeo intestinal anorexígeno produzido pelas células L do intestino. Recentes estudos têm demonstrado que em longo prazo a administração de oxintomodulina reduz a ingestão alimentar e o ganho de peso. Pesquisas em humanos têm verificado que o seu uso reduz o consumo energértico em 25%. Portanto, a oxintomodulina representa uma potente terapia anti-obesidade. Entretanto, o mecanismo de ação da oxintomodulina ainda é desconhecido. Atuais evidências sugerem que tem ação via receptor do peptídeo semelhante ao glucagon 1. Além disso, a literatura mostra que, juntamente com a adoção de hábitos saudáveis e a mudança do estilo de vida, a oxintomodulina pode proporcionar menor avanço da obesidade. Termos de indexação:Agentes anti-obesidade. Gastrointestinais. Hormônios. Obesidade. Peptídeos. Perda de peso. A B S T R A C T Since the discovery of leptin, great advances occurred in the characterization of hypothalamic mechanisms involved in the control of food intake and oxyntomodulin is currently recognized as a homeostasis energy regulator. This review discusses the most important interrelationships between the hormone oxyntomodulin and appetite, energy homeostasis and aspects of its role in nutritional biochemistry

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Evaluation of new leptin fragments on food intake and body weight of normal rats

Cited by 13 publications

References 44 publications

Myristic acid conjugation of [D-Leu-4]-OB3, a biologically active leptin-related synthetic peptide amide, significantly improves its pharmacokinetic profile and efficacy

Myristic acid conjugation of [D-Leu-4]-OB3, a biologically active leptin-related synthetic peptide amide, significantly improves its pharmacokinetic profile and efficacy

Cysteine cathepsin S processes leptin, inactivating its biological activity

Oxintomodulina e obesidade

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