New study links a protein to diabetes, obesity and cancer

July 9, 2013 | by

A gene may play as large a role in the cause of obesity as the foods we eat, according to new research from City of Hope.

City of Hope research has found that the protein RLIP76, modeled in above graphic, plays a significant role in weight gain, as well as controlling blood sugar, triglyceride and cholesterol levels.


The study, published in the Journal of Biological Chemistry, found that a protein, called RLIP76, produced by a specific gene, plays a significant role in obesity. Mice lacking the protein were resistant to gaining weight on a high-fat diet and had reduced blood sugar, cholesterol and triglyceride levels. In fact, they gained 40 percent less weight than mice that produced the protein after 12 weeks on a high-fat diet.

Sanjay Awasthi, M.D., a professor of Division of Molecular Diabetes Research and of medical oncology at City of Hope, is one of the study’s lead authors. “The American Medical Association recently defined obesity as a disease, but it’s long been viewed as a syndrome with many contributing factors and no single gene we can pin down — until now. This is conclusive evidence that a single protein dramatically affects development of obesity.”

Of course, such observations are based on animal data, which may or may not apply to humans, but they are undeniably provocative.

With about two-thirds of the U.S. population weighing in as overweight or obese, obesity is one of the nation’s most serious health problems and a global epidemic affecting 300 million people worldwide. Pinpointing this gene’s potential role offers new insights into the mechanism behind obesity — and why it’s so tough to fight, said Sharad Singhal, Ph.D., a research professor in the Division of Diabetes, Endocrinology & Metabolism at City of Hope.

In addition to being thinner after the high-fat diet regimen, the mice without the protein had lower levels of cholesterol and insulin in their blood streams.

“This suggests that a high-fat diet alone is not enough to cause high cholesterol, insulin resistance, obesity, metabolic syndrome or type 2 diabetes,” Singhal said. The protein appears to be an essential factor.

The study is the most recent the team has published examining RLIP76 and its role in disease. The protein is found on the surface of cells and acts as a pump to remove toxic agents that might come in contact with the cell.

Previous studies by Singhal and Awasthi found that cancer cells produce excessive amounts of RLIP76, which makes cancerous cells resistant to radiation and chemotherapy. The protein also plays a role in diabetes, and now obesity. Much study of cancer and other disease focuses on mutated genes leading to a loss of function that causes cancer. Awasthi says maybe researchers have been asking the wrong question.

“Instead, maybe we need to look for the genes that are never mutated in cancer, and this is one of them,” he said. “It’s always present in every type of cancer, and it’s increased in multiple diseases, including diabetes and obesity. Cancer, diabetes and obesity are linked to about 80 percent of all adult mortalities." This protein may play a role in all three.

City of Hope researchers are already working on the next step: identifying a drug that will effectively target the protein.

  • Sophia Ann-Marie McFoy

    Go science! Thanks City of Hope for being on the forefront of scientific discoveries :-) I was curious about how Lectins come into play and was wondering if you could provide the full title of the JOBC article?

  • Melissa

    So, SO excited about this! Where do we find the trial qualifications?

  • jessie dirickson

    how can i obtain the tablets protain RLIP76

    • Sethu Subramanian

      It is not lectin but LEPTIN. The former is a glycoprotein while the latter is a hormone involved in controlling the appetite. When the body is resistant to leptin, weight gain occurs similar to insulin resistance makes diabetes worse.

    • Sethu Subramanian

      You don't ingest this protein, even if available. This protein is reported to cause obesity. If your body makes it you need to counter it with drugs when they become available.

  • indzine

    How can we avoid this protein?

    • Sethu Subramanian

      Either you have that gene which makes this protein in your body or you don't. Pharma companies won't make money from those who don't have this gene innate. They will try to make drugs which will inhibit this protein which if effective will control weight gain. That is where the money is.

  • Jean

    Fascinating. I'm anxious to hear more results from your very important studies. As the child of two Diabetics, I've felt genetically doomed to become Diabetic myself. So, my feelings weren't too far off! My question is what do you think is causing more people to become obese now versus the past? It seems there are significant increases in so many diseases/conditions, from Autism to Alzheimer's. While it's obviously important to find treatments and cures for these, I think it's more essential we explore WHY this is all happening. Is it possible there are negative long term effects from things we use today and take for granted; things like artificial sweeteners, the use of more complicated medications, or even something as obscure as microwaves?

    • Dr, Subramanian

      There are two factors for health and illness. Nature and nurture. Nature has not changed in the last few hundred years. So the genes that you get from your ancestors are fairly constant. If your great-grandmother had diabetes you have a chance to get it too. Secondly how you live your life–eating, exercise, stress, other lifestyle habits–such as smoking, drinking, recreational drug use and several others— also affect your chances of getting diseases. Compared to earlier times genetic diseases have not increased. However, the population has increased— compared to 50 years ago it has perhaps doubled—and hence there are more people with the diseases. In addition, people live longer and ageing comes into picture too. Finally in earlier times people just died without being diagnosed or treated. Now science has advanced enough to detect all kinds of diseases–whether able to treat/cure or not.

  • Shirley A. Stegner

    My name is Shirley Stegner. I am a former cer patient there at City od Hope. I also have type 2 Diabetes and am a 100 pounds overweight. I was very interested to read the above article. Could it some day if not now help me. My sugar numbers are quite low, but I seem to get all the side effects of Diabetes anyway.I have quite a lot of neuropathy. I know everyone there is very busy, but may just a couple of words. My email is:
    shirley_stegner @ Thank you very much.

  • Shirley A. Stegner

    Breast cancer patient, that is.

  • Yolande Howard

    My question is if the protein RLIP76 typically removes toxins from a cell would that mean you would have to be very careful in removing it from the body and would removing the protein cause other more serious issues as well?
    I'm very interested in this clinical trial.

    • Dr, Subramanian

      This RLIP76 does not help a normal cell get rid of any toxins within the cell. The authors of the article contend that it helps to pump out any effects of radiation and chemotherapy that is administered to treat cancer patients which is why radiation and chemo treatment are not working well to treat cancer. What they are attempting to do now (they have taken a patent to that effect) is to inactivate that protein so that radiation and chemotherapy can do their job without interference from RLIP76. Removing the gene or the protein from the human body is impossible. What the authors have done is to create new mice by knocking out that gene when they create new mice from the sperm and egg.That strategy won't work for humans.

  • Rose Marie

    very interested as well, on more information on the protein RLIP76. I struggle losing weight and 75lbs overweight. I do not eat pork, beef, white flour, limit my intake on sweets to only Christmas holiday but never over eat sweets. Do not consume soda's, do not smoke or drink alcohol or use drugs. I eat leafy green vegetables daily. I was diagnosed with TIA (systems) August 31, 2012 and was placed on preventive medications. I was diagnosed with low thyroid as well. My biggest worry is my weight. Before my TIA episode I was walking 5 miles daily now I walk 1 or 2 miles every other day. It seem what I have experienced has slowed me down tremendously. My grandmother at age 70 did have diabetes. I am wondering since you mentioned "Ancestors Genes" that my TIA is due to genes.

    • Sethu Subramanian

      Rose Marie:
      The study mentioned here is quite preliminary and even if the conclusions prove right, it may take years and years before a drug can be synthesized, subjected to clinical trial and due processing. Even then it is not certain a drug will pan out. Remember leptin was supposed to be a wonder drug to cure obesity. It did not turn out to be so. Yes, your inherited genes do play a role in what kinds of diseases are in store for you. But that is not fate. You can counter it by taking appropriate measures. You can definitely delay the ill effects by eating right and walking 2 to 3 miles everyday briskly. Also at home spend the time walking around, standing, and spending energy that accumulates from eating. I suppose you mean transient ischemic attack by TIA. I would suggest drinking lots of water everyday to counter another stroke attack. When the blood thickens it can promote clot formation. What I am suggesting is all common sense and some research. Keep visiting your physician at the required times. Ask questions like "what if …". Your doctor should either give you the answers or he should say, "I don't know". If he shuts you up find another doctor. Eat a variety of vegetables, not just leafy ones alone. Also don;t eat too much spinach, rhubarb etc., which might produce kidney stones. Talk to a nutritionist about the kind of diet you should consume.

      • california2014

        Yes, I did mean Transient ischemic attack by TIA. So this protein is not something that one cannot just wash away with changing eating habits and drinking plenty of water?

        I enjoy gardening, digging up the ground planting vegetables, flowers in my garden, and keeping up with housework responsibilities as well. I do try to keep as active a possible; however, you are correct I must eat wider variety of vegetables, and increase my water intake is vital. Thank you for the information…I was not aware about spinach or rhubarb effects.

        Rose Marie

        • Sethu Subramanian

          Rose Marie:
          I am afraid certain genetic traits are hard to ward off. I think TIA has no correlation to RLIP76. I may be wrong. If you have the gene for RLIP76 and if the connection to obesity, cancer, and diabetes with RLIP76 is strong, then as the authors suggest, this protein has to be inhibited with drugs just like statins help to mitigate the synthesis of cholesterol in the body. Until such a drug comes to reality all bets are off. The wise thing to do is to eat lots of vegetables, fruits, and fiber besides regular walking everyday for 2 or 3 miles (if you can afford that in terms of time available) or bike 7 or 8 miles. Water drinking helps in several ways (no soda or beer) such as toxin removal from the body, and prevent dehydration (which is a forerunner for causing strokes)

  • Rose Marie

    Moreover, How can I avoid this protein?

  • Cristy

    Great..that's awesome information for people that are fat and on high-fat diets as opposed to high-carb diets. However, what percentage of fat Americans do you think are on high-fat diets rather than high-carb diets? Very, very few. Would this information still apply with a completely different diet? I don't think that it would be very scientific to say that these findings can be used no matter what the diet.

    So, my question is, why bother doing a study that's based on a diet that isn't the cause of most obesity in the USA (or probably any country)?

  • Elizabeth Glenn

    Is there any way to be part of the case study? I would be willing to be a participant. I have tried everything to lose weight except for the surgery but that's only because it is an exclusion of benefits with my insurance.
