The objectives of the present study were to examine the effects of dietary fat type and level of energy intake on hypothalamic leptin binding affinity and membrane fatty acid composition, circulating leptin levels, and body weight homeostasis in rats. Animals were fed diets containing tallow, safflower oil, or menhaden oil (20% wt/wt) for 10 wks, ad libitum or at 60% of ad libitum intakes. Specific leptin binding could not be detected in hypothalamic membrane homogenates; hypothalamic leptin levels were unaffected by diet or energy intake. Levels of tracer exceeding assay reference values were found in homogenates, suggesting intra-membrane binding. Excess tracer levels were weakly associated (p < 0.07) with the sum of hypothalamic phospholipid monounsaturates. Restriction lowered weight gain and food intakes (p < 0.0001 for both). In hypothalamic phospholipids, energy restriction lowered levels of 18:3(n-3) and increased levels of 20:1(n-9), 20:4(n-6), and 22:4(n-6) (p < 0.05, p < 0.02, p < 0.05, and p < 0.04, respectively). Fat type and energy level interactively affected hypothalamic levels of 20:4(n-6), 22:5(n-3) and 22:6(n-3) (p < 0.05, p < 0.006, and p < 0.05, respectively). Restriction lowered circulating leptin levels (p < 0.0001); overall plasma leptin levels were marginally associated (p < 0.07) with hypothalamic 16:0 concentrations. The results of the study support previous findings suggesting that leptin binding at the level of the hypothalamic membrane may not be detectable. The results also support the lack of a dietary fat effect on plasma leptin levels and levels of certain hypothalamic fatty acids, such as 20:4(n-6), 22:4(n-6), and 22:5(n-3), with energy restriction. The findings of the study suggest a link between increased membrane fluidity, increased binding affinity, and lower circulating leptin levels, promoting the possibility that the biological actions of leptin can be controlled through dietary effects on

Thesis (M.S.)--Auburn University, 2007. / Abstract. Vita. Includes bibliographic references (ℓ. 46-53)

Thesis (M.Sc.). / Written for the Dept. of Neurology and Neurosurgery. Title from title page of PDF (viewed 2008/12/07). Includes bibliographical references.

Thesis (MS)--Montana State University--Bozeman, 2009. / Typescript. Chairperson, Graduate Committee: James G. Berardinelli. Includes bibliographical references (leaves 72-87).

Thesis (M.S.)--University of Texas at El Paso, 2009. / Title from title screen. Vita. CD-ROM. Includes bibliographical references. Also available online.

Thesis (M.S.)--The University of North Carolina at Greensboro, 2008. / Title from PDF t.p. (viewed Jun. 4, 2009). Advisor: John Lepri; submitted to the Dept. of Biology. Includes bibliographical references (p. 55-59).

The aim of this thesis was to perform association analysis of UASMS1 polymor-phism in leptin gene with parameters of beef quality, studied on a group of Czech Fleckvieh bulls. The group of 236 bulls was genotyped by direct sequencing of the PCR product. Individual genotypes were processed into a database and statistical evaluation of association was performed by using SAS software. The UASMS1 polymorphism had a highly significant effect on palmitoleic acid content (p = 0.00006) and stearic acid content (p = 0.0005) between CT and TT genotypes. There was a significant value in myristoleic acid content (p = 0.0117) between genotypes CT and TT and in linolelaidic acid content between both genotypes CC and CT (p = 0.0340) and CC and TT (p = 0.0417). Values relating to the effect on dry matter content (p = 0.0746) and colour of meat (p = 0.0541) had only approaching evidentiary values. The influence of genotype on intramuscular fat content or other parameters of beef quality has not been demon-strated in this study.

Orientador: Licio Augusto Velloso / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas. / Made available in DSpace on 2018-08-17T07:03:20Z (GMT). No. of bitstreams: 1 Mansur_Eli_D.pdf: 1693041 bytes, checksum: a5b3d9f350100a50b16d835341ff4bc9 (MD5) Previous issue date: 2007 / Resumo: A leptina, hormônio com semelhança funcional e estrutural às citocinas, é conhecida por exercer, além das ações clássicas de controle da ingestão alimentar e termogênese, importantes funções na modulação das respostas do sistema imune. Alguns destes efeitos são dependentes da propriedade da leptina em modular a apoptose das células tímicas. Neste trabalho, utilizamos ratos Wistar para investigar os mecanismos moleculares envolvidos no controle, dependente da leptina, da apoptose no timo. A apoptose foi avaliada por citometria de fluxo e ELISA para determinação de nucleossomos, enquanto que a transdução do sinal foi avaliada por imunoprecipitação, imunoblot e microscopia confocal. O ObR estava expresso na maioria das células tímicas e a sua quantidade relativa reduziu-se progressivamente durante a maturação dos timócitos. A expressão do ObR estava co-localizada com JAK-2 e STAT-3, e a injeção aguda, in vivo , de leptina promoveu a fosforilação em tirosina de JAK-2 e o engajamento de STAT-3. O tratamento com leptina, também, levou à fosforilação em tirosina de IRS1 e fosforilação em serina de Akt. O tratamento crônico com leptina reduziu a apoptose tímica, e este efeito não foi inibido pelo AG490, um inibidor de JAK, mas foi significativamente inibido por LY294002, um inibidor de PI3-Quinase, e por um oligonucleotídeo antisense para IRS1. Portanto, a leptina inibe a apoptose em células tímicas via um mecanismo independente da ativação de JAK-2 mas dependente do engajamento da via IRS1/PI3-Quinase / Abstract: The cytokine-like hormone leptin is known to exert important functions on the modulation of immune responses. Some of these effects are dependent on the property of leptin to modulate the apoptosis of thymic cells. In the present study, we employed Wistar rats to investigate the molecular mechanisms involved in leptin-dependent control of apoptosis in thymus. Apoptosis was evaluated by flow cytometry and ELISA for nucleosome determination, while signal transduction was evaluated by immunoprecipitation, immunoblot and confocal microscopy. The ObR was expressed in most thymic cells and its relative amount reduced progressively during thymocyte maturation. ObR expression was co-localized with JAK-2 and STAT-3, and an acute, in vivo , injection of leptin promoted the tyrosine phosphorylation of JAK-2 and the engagement of STAT-3. The treatment with leptin also led to the tyrosine phosphorylation of IRS1 and serine phosphorylation of Akt. Chronic treatment with leptin reduced thymic apoptosis, an effect that was not inhibited by the JAK inhibitor AG490 but was significantly inhibited by the PI3-kinase inhibitor LY294002 and by an antisense oligonucleotide to IRS1. Thus, leptin inhibits the apoptosis of thymic cells through a mechanism that is independent of the activation of JAK-2 but depends on the engagement of the IRS1/PI3-kinase pathway / Doutorado / Medicina Experimental

No description available.

Vor dem Hintergrund der zunehmenden Prävalenz von Adipositas ist die Erforschung der zugrunde liegenden Pathomechanismen, unter anderem der Leptinresistenz, von großer Bedeutung. Der Schwerpunkt der vorliegenden Arbeit lag in der Etablierung und Validierung einer Methode zur Bestimmung der Bioaktivität von Leptin in Serum. Aufgrund des Vorhandenseins von Leptinbindungsproteinen erscheint nur der Teil des Serumleptins funktionell entscheiden, der tatsächlich den Leptinrezeptor erreicht und eine Bioantwort im Sinne einer Gewichtsreduktion auszulösen vermag. Der Bioassay basiert auf der Nutzung von Luciferase als Reportergen im HEK-293-Zellkulturmodell. Während der Validierung konnte gezeigt werden, dass der Test ein sensitives und spezifisches Verfahren zur Messung von Leptin im Serum darstellt. Problematisch blieb die Reproduzierbarkeit der Messergebnisse, so dass deren Interpretation im Vergleich mit Ergebnissen anderer Verfahren zum Nachweis von Leptin (Radioimmunoassay) sinnvoll erscheint. Der Luciferase-Bioassay wurde zur Bestimmung des Leptins im Serum adipöser Kinder eingesetzt, wobei eine statistisch signifikante Korrelation zwischen deren Bioaktivität und klinischen Markern der Adipositas gefunden wurde.