Cientistas descobrem nova proteína que contribui para a obesidade
Autor: Rubens Fernando Júnior | Publicado: 2011-10-17T13:37:00-07:00

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Uma pesquisa da
Universidade de Monash, na Austrália, realizada com auxílio de colaboradores
dos Estados Unidos, pode explicar mais um mecanismo que faz com que as pessoas
se tornem obesas. O estudo identificou uma nova proteína que inibe o hormônio
leptina no cérebro, um dos fatores que contribuem para a progressão da
obesidade mórbida. O estudo foi publicado nesta sexta-feira, 14 de outubro de
2011, no periódico americano Cell Metabolism, e é uma importante contribuição para
o desenvolvimento de novos tratamentos da doença.





A leptina (grego leptos = magro) foi identificada em 1994
como um produto do gene ob descrito
em camundongos. É um peptídeo formado por 167 aminoácidos, entretanto, circula
no sangue com apenas 146 aminoácidos ligados a uma proteína carregadora e sua
síntese pode ocorrer no tecido adiposo (adipócitos), placenta, músculo
esquelético, glândula mamária, epitélio gastrointestinal e no cérebro. Ela e
inúmeros outros hormônios – grelina, adiponectina e insulina – estão
correlacionados com a enfermidade do século.

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; A leptina, produzida
no tecido adiposo, age no hipotálamo que redistribui a sua ação. A sinalização
(complexo sistema de comunicação celular) na glândula pituitária (hipófise)
estimula as gônadas indicando o início da puberdade e da reprodução (Hormônio
Folículo Estimulante - FSH e Hormônio Luteinizante - LH ); as adrenais (Hormônio
Estimulante do Córtex das Adrenais – ACTH) regulando os estímulos adrenérgicos.
Porém, sua ação mais importante é no controle da ingestão alimentar e na
manutenção da homeostase corporal com o metabolismo de açúcares e lipídeos no
hipotálamo (ver imagem abaixo).

&nbsp;

&nbsp;



&nbsp; 

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No controle da
temperatura corporal, a leptina atuará no sistema nervoso simpática estimulando
a liberação de noraepinefrina na corrente sanguínea desencadeando uma cascata
enzimática, levando a formação das UCPs (Proteínas Desaclopadoras da
Fosforilação Oxidativa), a qual afetará diretamente o metabolismo de açúcares e
lipídeos, pois agem na última etapa da via da respiração celular, ou seja, toda
a energia contida em açúcares e lipídeos será transformada em calor sem a
formação da molécula de ATP.



Essa termogênese ocorre
exclusivamente no tecido adiposo marrom ou multilocular (assim denominado por
apresentar inúmeros citocromos em suas mitocôndrias), pois somente esse tecido
apresenta o gene para transcrição das UCPs. E como consequência desse processo,
o tecido adiposo branco ou unilocular (assim denominado por apresentar diversos
carotenoides dissolvidos na gordura) será responsável por aumentar a lipólise e
reduzir, logicamente, a lipogênese. Dessa forma, a ação regulada da leptina
pode controlar a quantidade de gordura corpórea e, portanto, a obesidade.



Esse mecanismo está
acoplado com a regulação da ingestão alimentar, pois ambos dependem do estímulo
que a leptina tem sobre a secreção de neuropeptídeos anorexígenos, os quais são
responsáveis por reduzir a ingestão de alimentos promovendo a sensação de
saciedade. Esses neuropeptídeos Y e neuropeptídios anorexígenos atuam em
conjunto com certos moduladores hipotalâmicos (POMC – Pró-Ópio-Melanocortina,
CART – Fator de Transcrição Cocaína-Anfetamina Dependente) de forma a inibir os
demais peptídeos responsáveis por um aumento na ingestão de alimentos
(neuropeptídeos orexígenos), quando esse mecanismo falha, por exemplo, devido a
um problema nos receptores do hormônio, a consequência é a obesidade (ver
imagem abaixo).







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"A resposta do
corpo à leptina diminui em pessoas obesas ou com sobrepeso, como se elas se
tornassem resistentes ao hormônio", explica Tony Tiganis, principal autor
da pesquisa e professor do Instituto de Obesidade e Diabetes da Universidade de
Monash.



Antes de o grupo
identificar uma nova proteína inibidora de leptina no cérebro, duas outras já
eram conhecidas. Testes em camundongos revelaram que essa terceira proteína se
tornou mais abundante com o ganho de peso, aumentando a resistência à leptina e
apressando a progressão da obesidade mórbida. É como se fosse um círculo
vicioso: à medida que a pessoa fica obesa, a resistência à leptina torna o
processo de perder peso mais difícil. O estudo também mostrou que esses três
reguladores negativos do hormônio produzem efeitos em diferentes estágios, dado
que pode ser fundamental para o desenvolvimento de novos remédios.



"Drogas que visam
um desses reguladores negativos já são conhecidas em testes clínicos para
diabetes tipo 2. Porém, nossa pesquisa mostra que, em termos de sensibilidade à
leptina em obesos, focar em apenas uma dessas proteínas não é o suficiente.
Todos os três reguladores devem ser desligados", explica Tiganis.



O estudo ainda mostrou
que o ganho de peso foi amplamente evitado em camundongos geneticamente
modificados que tiveram dois dos reguladores negativos eliminados do cérebro. A
partir daí, os pesquisadores passarão a realizar outros testes para determinar
o que acontece quando as três proteínas são neutralizadas, e descobrir se isso
é o suficiente para evitar a progressão da obesidade.



"Simplesmente
dizer às pessoas para comerem menos e se exercitarem mais não será o suficiente
para reverter essa tendência à obesidade. Há uma necessidade de desenvolvermos
novas drogas que auxiliem na escolha da melhor dieta e exercícios físicos, para
que todos esses fatores previnam e tratem juntos essa doença", diz
Tiganis.
&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;

Veja o quadro abaixo comparando os níveis de leptina quando está sob
efeitos orgânicos e ambientais.

&nbsp;



&nbsp;

&nbsp;Fonte: Exame - Adaptado.