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Why obese bodies resist leptin

MONASH (AUS) — Researchers have discovered how a key causal component of obesity—resistance to the hormone leptin—develops.

Tony Tiganis, lead author of a study published in the journal Cell Metabolism, says our bodies produce leptin in response to increasing fat deposits.

“Acting on a part of the brain called the hypothalamus, leptin instructs the body to increase energy expenditure and decrease food intake, and so helps us maintain a healthy body weight,” says Tiganis, a professor in the biochemistry and molecular biology department at Monash University.


Tony Tiganis (right) with research team member Kim Loh. (Credit: Monash University)

“The body’s response to leptin is diminished in overweight and obese individuals, giving rise to the concept of ‘leptin-resistance’. We’ve discovered more about how ‘leptin-resistance’ develops, providing new directions for research into possible treatments.”

Two proteins are already known to inhibit leptin in the brain and Tiganis’ team have discovered a third. In mice, this third protein becomes more abundant with weight-gain, exacerbating leptin-resistance and hastening progression to morbid obesity.

The study showed that the three negative regulators of leptin take effect at different stages, shedding light on how obesity progresses.

“Drugs targeting one of the negative regulators are already in clinical trials for Type 2 Diabetes, however, our research shows that in terms of increasing leptin-sensitivity in obesity, targeting only one of these won’t be enough. All three regulators might need to be switched off,” says Tiganis.

The study showed that high fat diet-induced weight gain is largely prevented in genetically modified mice when two of the negative regulators are deleted in the brain.

“We now have to determine what happens when all three negative regulators are neutralized. Do we prevent high fat diet-induced obesity?”

Tiganis says the more that is known about obesity, the better equipped scientists are to develop drugs to support good diet and exercise choices.

“Humans have a deep-seated attraction to overeating and nutrient-rich food, inherited from our hunter-gatherer ancestors. Now that food is more readily available and our lifestyles are less active, our evolutionary drive to overeat is becoming problematic.”

More than four million Australians are obese and if current trends continue, by 2020, more than 80 percent of adults and almost one third of children will be overweight or obese. Studies indicate that obesity and related health issues cost Australians more than $56 billion a year.

“Simply telling people to eat less and exercise more is not going to be sufficient to reverse the obesity trend. There is a pressing need to develop novel drugs that complement diet and exercise to both prevent and treat this disease,” says Tiganis.

More news from Monash University: www.monash.edu.au/news/

chat6 Comments

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6 Comments

  1. Kloooo

    I’ve never seen such blatant bullshit by a researcher. But, what else do you expect from a bunch of half-wits who hide from real life in their labs, then go home and jerk off to the cute girls they saw around campus. That is, if they grew tired of their stash of kiddie porn.

    People are fat because they lack the ability to say no to a piece of chocolate cake. Why do you think all these fat people who have stomach reduction surgeries lose weight? Is it magic? Fuck no, it’s because they are physically restricting the amount of calories they can eat.

    If these “researchers” wanted real change, they could get off their ass and go march down the leaders who are allowing the food industry and government to fuck over people’s minds with propaganda.

    Oh wait, that’s right. Researchers would never actually get involved with something that requires real work and risk.

  2. Edward Kerr

    “Humans have a deep-seated attraction to overeating and nutrient-rich food, inherited from our hunter-gatherer ancestors”

    To blame the present epidemic of obesity on our evolutionary development is, as kloooo says, BS.
    It is related to what we eat as much as to the amount that we eat.

    The drive for shelf life and cheap ingredients to increase profits is at the core of the problem, not evolution.

    It;s true that eating too much of anything is not a good idea, simple gluttony cannot account for the scope of the obesity problem that is destroying so many lives and taxing our ability to pay for “sick care”

    Ed

  3. Sammi

    I used to think like Klooo that fat people ‘had it coming’ because of their gluttonous ways…that is until I became one. Over the years I watched my weight climb drastically even with a very healthy lifestyle, avoiding the GMO stuff, no MSG, grass-fed meat, organic veggies, no soft drinks, I’m even experimenting with going raw at least 80% now. I have always felt great, just looked horrible. Now that I have been tested and found I have hypothyroidism and am critically vitamin D deficient, I hope to turn this all around. Let’s not judge others until we have walked in their shoes. Mr. Kerr is correct that simple gluttony is not always the answer to obesity. Yes, in the past I have been guilty of overeating, but now people are amazed at how little I eat. I am enjoying going raw. I have much more energy and no carb cravings! I am learning to make myself get up from the computer periodically and MOVE! I’ll never be a vegan, but I have a little more respect for the vegetarian life-style than I used to have. Our biggest problems with food appear to be from a government that wants us all to die, judging from the way they push vaccines and GMO crap on us and outlaw the healthy stuff.

  4. Muriel

    One of the largest contributing factors to this obesity epidemic seems to actually be the bad dietary advice being given. I doubt that I can put it is as elegantly as Dr. Eenfeldt when he spoke at the Ancestral Health Symposium 2011, but the basic message was the obesity epidemic started when we were told fat is bad. Evidence which is outlined in his lecture The Food Revolution” (http://www.youtube.com/watch?v=FSeSTq-N4U4) suggests that all the low fat products we consume containing increased amounts of sugar are actually fuelling the obesity epidemic. Please take the time to watch the lecture as it is likely to completely change your dietary decisions.

    Also, Kloo I think you were quite harsh in your narrow minded comments. These researchers are obviously taking action and dedicating themselves to help others who cannot help themselves. Not all people who are obese have the inability to say no to a piece of chocolate cake.

  5. steve

    Klooooo…
    stop barking like a dog….

  6. zeezee

    Klooo, it is narrow minded people like you who are making the problem worse. Weight gain and inactivity are SIDE effects of obesity (itself a metabolic issue), not the CAUSE.
    When someone grows fat in certain areas (like women growing breasts) or is a certain height, what do we pin it on? Genes and hormones. Well guess what – the same is true for how outward we grow. There are a myriad of factors involved in obesity. Namely, the role of insulin prohibiting mobilisation of fat stores, resulting in cells that think they’re starving and drive the body to find more fuel or decrease activity. Insulin is spiked primarily through carbohydrate rich foods. And yes, in that instance, the supermarket shelves stocked with crap certainly aren’t helping. However, the issue is not nearly as simple as you think it is. If overweight people try to lose weight by sticking to the conventional wisdom, they end up trying to restrict their calories (the body’s homeostatic mechanisms don’t allow this long term), whilst eating foods like oats, wholegrain toast, fruit, ‘fat free’ yoghurt etc… All incredibly carb rich and not conducive to weight loss.

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