Retrospectacle: A Neuroscience Blog

In the February issue of the Journal of Clinical Investigation, U-M researcher Liangyou Rui, Ph.D. and his team report their findings on a protein called SH2B1, a protein in brain cells may act as a linchpin in the body’s weight-regulating system. It seems to play a key role in signaling in regards to fat storage, sugar use, energy balance and weight.

The experiments were performed in two types of mice that the team altered genetically so that they only expressed a unique form of the SH2B1 protein in their brain cells. They zeroed in on SH2B1’s activity in the hypothalamus: the area of the brain that coordinates signals from the brain and body relating to food, hunger, and the balance of energy and nutrients in the body.

Rui and his team have already shown that mice that lack the gene for SH2B1 become obese and diabetic. [Unrelated side note: a friend pointed out to me that obese mice are used as models when studying diabetes. There’s that much of a strong correlation.] These mice are unable to respond to signals sent to the brain by leptin and insulin which would normally result in a decrease in appetite, food intake, and fat storage. In a nutshell, mice that don’t have this gene get really fat, as their brain can’t communicate to stop eating.

Rui also developed mice that made an excessive amount of SH2B1. These mice did not become obese or diabetic even after being fed a high-fat diet that would have resulted in obesity in normal mice. This suggests that an over-active signaling system mediated by SH2B1 might protect the body from excessive fat storage and from diabetes.

“Obesity, whether in mice or humans, is the product of an altered balance between energy intake and energy use. The imbalance is linked to alterations in leptin and insulin signaling that lead to excess weight gain and Type 2 diabetes, respectively,” says Rui, an assistant professor of molecular and integrative physiology at U-M. “SH2B1 appears to play a key regulatory role in this system, through its direct influence on the processing of leptin and insulin signals in cells of the brain’s hypothalamus.”

Get the free full-text paper here.


  1. #1 J-Dog
    February 2, 2007

    IMO the BEST result will not having to be subjected to weight-loss advertising anymore! Hopefully these brave, cutting-edge mice will be given a trip to DisneyWorld, if not Stolkholm, as a reward.

  2. #2 Shelley Batts
    February 2, 2007

    I’m with ya on that one. If I never again have to hear…”When is a diet pill worth $150 a bottle?”…it’ll be too soon.

  3. #3 steve
    February 2, 2007

    so when will there be no more fat people?

  4. #4 Shelley Batts
    February 2, 2007

    Steve, stop that! Are you trying to goad the hoards? 😛

  5. #5 Charlie (Colorado)
    February 2, 2007

    Hmmm. Did you mean “hordes” or are you making a pun?

    Anyway, seriously, as one of the adipose-enhanced since childhood, this is something that fascinated me, especially after I got into medical school classes and started really learning something about the various homeostatic mechanisms in the body … not to mention getting interested in social mechanisms in science. The evidence that there is some kind of real physiological difference between heavy people and skinny people has been building up for twenty years — but an amazing number of otherwise sophisticated people will still say that there is no difference between fat people and skinny people except that fat people have no self-control, or something similar.

  6. #6 steve
    February 3, 2007

    sorry 😉 I can’t help myself sometimes. haha..

  7. #7 mindlesley
    November 14, 2008

    Charlie couldn’t agree more. Am an Aussie, type 1 1/2, diabetic, Med school dropout. Good luck with your Phd and any sanity issues, Shelley. I found myself facing medical rejection of kidney transplantation because of 115 kgs of unwanted avoirdupois. Am on insulin and home Hemodial. I was findin’ it hard to lose said weight. Read in journal Obesity of links between insomnia and obesity. Decided to take melatonin 3mg each evening. Wacko! weight started to roll off. Now on list. Now am 95 kgs and still losong weight only more slowly. My endocrinologist reckons I’m on to somethin’. Maybe a chemical cascade or a serial turning on (or off) of genes that either my early environment, epigenetics or later lifestyle left in a obeseogenic state. I didn’t lose my appetite, but for first time in life knew when I was “full”. I also woke with light in mornings, slept thru’ night, had more energy and didn’t “night eat”. Also my restless leg syndrome improved markedly. I realise one experience is only an interesting anecdote, so don’t advise others to try my approach without specialist advice. PS. Scientists are trialing melatonin for Dialysis patients in Holland and other places. Your newbie and already devoted admirer, Mindlesley

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