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Targeting mitochondria to combat obesity

by Heather Buschman, Ph.D. on September 3, 2010 at 11:53 am | 4 Comments

How is fat tissue from an obese person different from a thin person’s fat tissue? Dr. Sheila Collins and her colleagues at Sanford-Burnham’s Diabetes and Obesity Research Centerrecently discovered one major distinguishing feature – fat tissue from obese people doesn’t oxidize fatty acids as well as that from thinner people.Fat cells use fatty acids for energy. But in response to adrenaline, fat tissue can also release fatty acids into the bloodstream for use by other tissues, such as heart and muscle. This latest study, published in the journal Diabetes, revealed that obese fat tissue was not as good as non-obese fat tissue at consuming fatty acids for energy. This might be one of the reasons why obese fat tissue releases more fatty acids into the bloodstream.  And although fatty acids are an important source of energy for other tissues, too much of it in the blood – a condition frequently seen in obesity – is believed to lead to type 2 diabetes and cause detrimental heart problems.

Now the trick is to figure out how to increase fatty acid oxidation in obesity. Not only would this reduce organ damage, but it would increase energy expenditure and – theoretically – reduce body weight. Dr. Collins is trying to do just that. In this latest study, she and her colleagues provide new clues to the role mitochondria (the ‘powerhouse’ of the cell) plays in oxidizing fatty acids in one type of fat tissue called white fat.

“The main job of the mitochondria is to use oxygen, burn carbon substrates like fatty acids, and make energy in the form of a chemical known as ATP,” Dr. Collins explained. “ATP is the currency of the cell. Like money, you have to have it in order to do things. In this case, cells need ATP to divide, make new proteins, store fat or do anything else a cell needs to survive.”

One way that fatty acid oxidation can be increased is by uncoupling the mitochondria, or increasing the ‘leakiness’ of its inner membrane. Since the inner membrane is where most of the electrochemical reactions occur, uncoupled mitochondria have to work harder to oxidize more fatty acids in order to produce ATP. The result is more energy burned. This uncoupling process is extremely active in a type of fat called brown fat. But since adults have a lot more white fat than brown fat, increasing a little bit of uncoupling in a lot of white fat just might lead us to new ways of burning it.

Many years ago, people tried to treat obesity with a drug that globally uncouples mitochondria, but the negative side effects (including death) halted this approach. The knowledge provided by this new study provides more hope that smarter anti-obesity therapies can be designed that more carefully balance mitochondria uncoupling and fatty oxidation without serious consequences.

Tags: fat, Lake Nona, metabolism, mitochondria, research publications, Sheila Collins

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4 Comments

  1. Heather Buschman says:
    June 13, 2011 at 8:40 am

    Dear David,

    Dr. Collins suggests you contact Drs. Steve O’Rahilly and Sadaf Farooqi at the University of Cambridge, UK – they work on the genetics of obesity.

    Hope that helps!

    Best,
    Heather

    Reply
  2. Heather Buschman says:
    October 5, 2010 at 12:06 pm

    Hi David –

    At this stage, these studies are focused only on the fundamental mechanisms guiding cellular function, meaning Dr. Collins and her colleagues mostly work with cells and proteins in the laboratory, rather than with patients. But thank you very much for your offer and your interest in this research!

    Cheers,
    Heather

    Reply
  3. David Byrne says:
    October 4, 2010 at 10:32 am

    I don’t Know if this would be of any assistance to you in your research, but I come from a family of five boys, all brought up together on the same diet, yet despite being the most active,fittest and strongest I alone have struggled against obesity all my life. At times I have been as heavy as 31 stones, currently around 26 stones, at 5’7″ not good. Diets do work, but after years you do get fed up never being able to relax and not worry about what you eat, even when in my 20s and a very able weightlifter, one of the top in southern England, when all my freinds were trying to eat as much as possible, To the point, as three of my younger brothers are still here,would you perhaps like to do comparison tests ?. If this would help you in your research I would be more than willing to assist.

    Yours sincerely

    David Byrne

    Reply

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