Cientistas dos EUA transformam 'gordura ruim' em 'gordura boa'

Cientistas norte-americanos dizem ter encontrado uma maneira de transformar gordura corporal em um tipo de gordura que queima calorias e diminui o peso.

A informação foi publicada nesta terça-feira no site da "BBC News".

A equipe de Johns Hopkins realizou o experimento em ratos, mas acredita que o mesmo poderia ser feito em seres humanos, o que acende a esperança de uma nova ferramenta para combater a obesidade.

A modificação da expressão de uma proteína ligada ao apetite não só reduziu o consumo de calorias e o peso dos animais, como também transformou a composição de gordura corporal dos ratos.

A gordura "má" branca transformou-se em gordura "boa" marrom, segundo relatório publicado na revista "Cell Metabolism".

A gordura marrom é abundante em bebês, que a usam como fonte de energia para gerar calor corporal, gastando calorias ao mesmo tempo.

Mas à medida que as pessoas envelhecem, grande parte da gordura marrom desaparece e é substituída pela gordura branca, "ruim", que se manifesta como um pneu sobressalente em torno da cintura.

Especialistas acreditam que estimular o organismo a produzir mais gordura marrom em vez de gordura branca pode ser uma maneira útil para controlar o peso e prevenir a obesidade, além de outros problemas relacionados à saúde, como diabetes tipo 2.

EXPERIMENTO

Sheng Bi e seus colegas da Universidade Johns Hopkins School of Medicine realizaram um experimento para averiguar a supressão de uma proteína estimuladora do apetite, chamada NPY, diminuiria o peso de ratos.

Quando silenciaram a proteína no cérebro dos roedores, descobriram a diminuição do seu apetite e ingestão alimentar.

Mesmo quando os ratos foram alimentados com uma dieta muito rica em gordura, ainda conseguiram perder mais peso que os roedores que tinham pleno funcionamento da NPY.

Os cientistas compararam então a composição da gordura dos animais e encontraram uma mudança interessante.

Nos ratos com a NPY silenciada, um pouco da gordura ruim branca tinha sido substituída pela gordura boa marrom.

Os pesquisadores estão esperançosos com a possibilidade do experimento ser realizado em pessoas, injetando células-tronco de gordura marrom sob a pele para queimar a gordura branca e estimular a perda de peso.

De acordo com Bi, "se o corpo humano conseguisse transformar gordura ruim em boa, que queima calorias em vez de armazená-las, poderíamos acrescentar uma ferramenta séria para enfrentar a epidemia de obesidade. "Somente mais pesquisas nos dirão se isso é possível."

Anjo da guarda cardíaco emite alerta antes de ataque do coração

Socorro cardíaco

Quando um ataque do coração começa, um cronômetro é disparado.

A cada minuto que passa, mais tecido cardíaco é privado de sangue, o que o faz deteriorar-se ou mesmo morrer.

A fim de minimizar os danos ao coração, o fluxo de sangue deve ser restaurado o mais rapidamente possível, ou os efeitos podem ser graves, muitas vezes até fatais.

Pesquisas mostram que o período de tempo entre o início de um ataque cardíaco e o início do tratamento é fundamental para aumentar as chances de sobrevida.

Alarme de ataque cardíaco

Então, que tal se um alarme soasse no início de um ataque cardíaco, sinalizando a necessidade imediata de assistência médica, antes até que o próprio paciente possa pedir socorro?

É justamente isto que estão desenvolvendo pesquisadores da Universidade Northwestern, nos Estados Unidos.

Um sensor aciona um pager que os pacientes carregam consigo quando ocorrem alterações no coração ou quando o médico desconfia que o risco de ataque cardíaco de um paciente está elevado demais.

O objetivo dos pesquisadores é tornar a tecnologia capaz de reconhecer os primeiros sinais de ataque cardíaco, até duas horas antes que ele se manifeste clinicamente.

Assim, os pacientes poderão procurar ajuda mais rapidamente.

"Embora as taxas de sobrevivência tenham melhorado ao longo dos últimos anos, muitos pacientes ainda morrem de ataques cardíacos a cada ano," comenta Liviu Klein, um dos cardiologistas participantes da pesquisa. "Se pudermos identificar um ataque cardíaco mais cedo, poderemos ser capazes de salvar mais vidas."

Antes dos sintomas

Ao todo, são 50 centros nos Estados Unidos participando dos testes do ALERTS, um dispositivo implantável destinado a detectar um ataque cardíaco antes que ele se manifeste na forma de sintomas sentidos pelo paciente.

Do tamanho de uma moeda de um dólar, o aparelho monitora a atividade do coração 24 horas por dia, sete dias por semana, usando um fio inserido no músculo cardíaco para monitorar constantemente a sua atividade elétrica.

Quando ocorrem mudanças, como a falta de oxigênio no coração, uma antena envia um sinal para um pager que o paciente carrega, avisando que um ataque cardíaco é iminente.

"Sintomas de ataques cardíacos são frequentemente mal interpretados, fazendo com que os pacientes retardem o tratamento," diz Klein. "Este dispositivo deixa claro que a atenção médica é necessária, permitindo que o paciente procure ajuda de forma rápida e proporcionando-nos uma oportunidade de iniciar o tratamento antes que um ataque de coração resulte em danos irreversíveis."

Minimamente invasivo

O dispositivo é primariamente projetado para pacientes que já sofreram um ataque cardíaco e estão em alto risco de sofrer outro ataque cardíaco.

Ele é implantado como um marca-passo, mas através de um procedimento cirúrgico minimamente invasivo, e tem o potencial de detectar um ataque cardíaco nos seus estágios mais iniciais.

Technique Developed for Measuring Stressed Molecules in Cells

ScienceDaily (May 3, 2011) — Biophysicists at the University of Pennsylvania have helped develop a new technique for studying how proteins respond to physical stress and have applied it to better understand the stability-granting structures in normal and mutated red blood cells.

Rendering of red blood cells. Biophysicists at the University of Pennsylvania have helped develop a new technique for studying how proteins respond to physical stress and have applied it to better understand the stability-granting structures in normal and mutated red blood cells. 

The research was conducted by Dennis Discher and Christine Krieger in the Molecular and Cell Biophysics Lab in Penn's School of Engineering and Applied Science, along with researchers from the New York Blood Center and the Wistar Institute.

Discher's research was published online in the journal Proceedings of the National Academy of Sciences.

In stark contrast with much of the architecture people interact with every day, the internal architecture of the human body is predominantly soft. Other than bones, all of the organs, tissues and structures in the body are pliable and flexible and need to be that way in order to work.

The Discher lab's research aims to understand what keeps these flexible structures stable, especially when they are under constant physical stress. Discher selected red blood cells as a model for this stress, as they make a complete lap of the turbulent circulatory system every few minutes but survive for months.

"Red blood cells are disks, and they have proteins right below the membrane that give it resilience, like a car tire," Discher said. "The cells are filled with hemoglobin like the tires are filled with air, but where the rubber meets the road is the exterior."

To measure stress in that membrane on an atomic level, the Discher team needed a way to track changes to the shape of those supporting proteins. They found an ideal proxy for that stress in the amino acid cysteine.

Proteins are long chain of amino acids that are tightly folded in on themselves. The order and chemical properties of the acids determine the locations of the folds, which in turn determine the function of the protein. Cysteine is "hydrophobic"; it interacts poorly with water and so it is usually on the inside of a protein. And because stress changes the shape of these folded proteins, Discher reasoned that measuring the degree to which cysteine is exposed would in effect measure how stressed the protein and cells containing it are.

Discher's team simulated the shear forces originating from the beating heart, which forcefully pumps blood and ultimately pulls apart the folds that keep cysteine on the inside of proteins at the red blood cell membrane, allowing it to bind with a fluorescent marker dye. The team could visually confirm that more stressed cells were more fluorescent under the microscope but actually tested the levels of marked cysteine using mass spectrometry.

"Just like a polymer engineer designing a tire, we're looking at the relationship between the chemical makeup and the physical stability of the structure and how it performs," Discher said. "We can use this technique to look at the relationship between structure, flexibility and function."

Investigating the structural elements of blood cells could pave the way to breakthroughs for human health.

"How long can blood be stored? Why are there no good blood substitutes? There are a lot of things we don't understand about the forces cells can sustain before fragmenting and falling apart, especially when we consider age and mutations," he said.

The Discher team studied the mutated blood cells that result in disorders known as elliptocytosis; cells are elliptical, rather than round, and therefore have shorter functional lifespans. These elliptical cells are often missing a chemical "rivet" that anchors the support proteins to the outer membrane, which means that stress causes them to "disassociate," or disconnect, rather than unfold.

That kind of structural change is crippling to the function of anatomical structures like blood cells. The flexibility provided by unfolding is therefore key to their overall stability.

"At least for this cell, the first mechanism of response is to unfold proteins and keep the interactions between proteins the same," Discher said. "That constant back and forth with unfolding within these cells as the cells flow and distort while in the blood stream, allows their architecture to be maintained."

Discher and his colleagues plan to use their cysteine-mass-spectometry technique to investigate the role of softness and flexibility in responding to stress in other biological systems, particularly stem cells, and to better understand why those traits are intrinsic to life on this planet.

Along with Discher and Krieger, the research was conducted by Xiuli An and Narla Mohandas of the New York Blood Center and Hsin-Yao Tang and David W. Speicher of the Wistar Institute.

The research was supported by the National Institutes of Health.

Removable 'Cloak' for Nanoparticles Helps Them Target Tumors

ScienceDaily (May 3, 2011) — MIT chemical engineers have designed a new type of drug-delivery nanoparticle that exploits a trait shared by almost all tumors: They are more acidic than healthy tissues.

The outer layer of this nanoparticle (in yellow) falls off in an acidic environment.

Such particles could target nearly any type of tumor, and can be designed to carry virtually any type of drug, says Paula Hammond, a member of the David H. Koch Institute for Integrative Cancer Research at MIT and senior author of a paper describing the particles in the journal ACS Nano.

Like most other drug-delivering nanoparticles, the new MIT particles are cloaked in a polymer layer that protects them from being degraded by the bloodstream. However, the MIT team, including lead author and postdoctoral associate Zhiyong Poon, designed this outer layer to fall off after entering the slightly more acidic environment near a tumor. That reveals another layer that is able to penetrate individual tumor cells.

In the ACS Nano paper, which went online April 23, the researchers reported that, in mice, their particles can survive in the bloodstream for up to 24 hours, accumulate at tumor sites and enter tumor cells.

A new target

The new MIT approach differs from that taken by most nanoparticle designers. Typically, researchers try to target their particles to a tumor by decorating them with molecules that bind specifically to proteins found on the surface of cancer cells. The problem with that strategy is that it's difficult to find the right target -- a molecule found on all of the cancer cells in a particular tumor, but not on healthy cells. Also, a target that works for one type of cancer might not work for another.

Hammond and her colleagues decided to take advantage of tumor acidity, which is a byproduct of its revved-up metabolism. Tumor cells grow and divide much more rapidly than normal cells, and that metabolic activity uses up a lot of oxygen, which increases acidity. As the tumor grows, the tissue becomes more and more acidic.

To build their targeted particles, the researchers used a technique called "layer-by-layer assembly." This means each layer can be tailored to perform a specific function.

When the outer layer (made of polyethylene glycol, or PEG) breaks down in the tumor's acidic environment, a positively charged middle layer is revealed. That positive charge helps to overcome another obstacle to nanoparticle drug delivery: Once the particles reach a tumor, it's difficult to get them to enter the cells. Particles with a positive charge can penetrate the negatively charged cell membrane, but such particles can't be injected into the body without a "cloak" of some kind because they would also destroy healthy tissues.

The nanoparticles' innermost layer can be a polymer that carries a cancer drug, or a quantum dot that could be used for imaging, or virtually anything else that the designer might want to deliver, says Hammond, who is the Bayer Professor of Chemical Engineering at MIT.

Layer by layer

Other researchers have tried to design nanoparticles that take advantage of tumors' acidity, but Hammond's particles are the first that have been successfully tested in living animals.

Jinming Gao, professor of oncology and pharmacology at the University of Texas Southwestern Medical Center, says it is "quite clever" to use layer-by-layer assembly to create particles with a protective layer that can be shed when the particles reach their targets. "It is a nice proof of concept," says Gao, who was not part of the research team. "This could serve as a general strategy to target acidic tumor microenvironment for improved drug delivery."

The researchers are planning to further develop these particles and test their ability to deliver drugs in animals. Hammond says she expects it could take five to 10 years of development before human clinical trials could begin.

Hammond's team is also working on nanoparticles that can carry multiple payloads. For example, the outer PEG layer might carry a drug or a gene that would "prime" the tumor cells to be susceptible to another drug carried in the particle's core.

Protein Identified as Enemy of Vital Tumor Suppressor PTEN

ScienceDaily (May 3, 2011) — A protein known as WWP2 appears to play a key role in tumor survival, a research team headed by a scientist at The University of Texas MD Anderson Cancer Center reports in an advance online publication of Nature Cell Biology.

Their research suggests that the little-studied protein binds to the tumor-suppressing protein PTEN (phosphatase and tensin homologue deleted on chromosome 10), marking it for destruction by proteasomes, which degrade proteins and recycle their components.

PTEN plays a role regulating the cellular reproduction cycle and prevents rapid cell growth, a hallmark of malignant cells. Its gene is mutated or deleted in many types of cancer, the researchers noted.

The WWP2 (atrophin-1 interacting protein 2) protein was discovered in the laboratory of Junjie Chen, Ph.D., professor and chair in MD Anderson's Department of Experimental Radiation Oncology and senior author of the paper.

"We were trying to find regulators of PTEN when we isolated the protein WWP2 as a putative PTEN-associated protein," Chen said. He noted that WWP2 caught the researchers' attention because it is similar to the NEDD4-1 protein, which has been proposed as a regulator of PTEN function.

First suspect doesn't affect PTEN

WWP2 is an E3 ubiquitin ligase in the NEDD4-like protein family. Ubiquitins attach to other proteins, labeling them for degradation by proteasomes. NEDD4-like proteins play important roles regulating gene transcription, embryonic stem cells, cellular transport and activation of T cells.

"But when NEDD4-1 is deleted in mice, researchers have not seen a clear change in PTEN protein level," Chen noted. "These findings suggest that there may be other PTEN regulators.

"Because WWP2 is part of the NEDD4-like family, we decided to take a look at it to see if it's the real regulator of PTEN," Chen continued. "When you knock down WWP2, you see an increase in PTEN level, whereas with WWP2 overexpression you can see a decrease in PTEN. This finding indicates that WWP2 may be involved in PTEN's regulation."

Overall, the study results suggest that WWP2 can regulate PTEN stability, Chen said.

Possibly a cancer-driving gene

The team uncovered evidence that WWP2 is a potential oncogene -- a driver in tumor formation and growth. In one experiment, mice with normal WWP2 developed prostate cancer tumors after nine weeks that were more than three times the size of tumors in mice with WWP2 silenced.

Chen noted that more research is needed to determine whether WWP2 is functionally important in tumors or in tumor formation. "We need to look at real tumor samples to determine whether tumors with reduced PTEN expression could result from the overexpression of WWP2."

He added that some early studies suggest that WWP2 may operate in tumors, but a correlation between WWP2 overexpression and PTEN downregulation in tumors has not been established.

This work was supported in part by a grant from the Department of Biotechnology, Ministry of Science and Technology, India, a U.S. Department of Defense Era of Hope Research Scholar Award, an NIH Specialized Program of Research Excellence award to Mayo Clinic, and a National Cancer Institute grant to MD Anderson. Also, fellowship support came from the Department of Biotechnology, Council of Scientific and Industrial Research and University Grants Commission, India, and support from the Institute of Life Sciences, Hyderabad, India.

Co-authors with Chen are first author Subbareddy Maddika, Ph.D, Sridhar Kavela, Neelam Rani, and Vivek Reddy Palicharla, all of the Laboratory of Cell Death and Cell Survival, Centre for DNA Fingerprinting and Diagnostics in Nampally, Hyderabad, India; Jenny Pokorny and Jann Sarkaria, M.D., of the Mayo Clinic, Rochester, Minn.