Specific protein the answer to rising obesity?
8/19/2005- One protein could be the answer to rising levels of obesity, say US researchers investigating why some mice, like many obese consumers, cannot stop eating.



Scientists at the University of Michigan Medical School studied mice to find out what causes their over-eating and morbid obesity.

Science is dedicating increasing time and resources to improve our knowledge of the growing phenomenon of obesity. Defined as a Body Mass Index over 30, obesity is a risk factor for a host of illnesses including heart disease, hypertension, diabetes and respiratory disease.

But fresh figures released recently show numbers are far from leveling off, with more than 200 million adults across the EU overweight or obese.

And far from being an adult problem, the number of European kids overweight is rising by a hefty 400,000 a year, according to the data from the International Obesity Task Force (IOFT).

Adding salt into the wounds, costs are high. Estimates claim obesity consumes about 5 per cent of total health care budgets in the EU.

But the latest research from the US could shed further light on why consumers overeat. Liangyou Rui, an assistant professor of molecular and integrative physiology in the U-M Medical School, claims the answer is SH2-B – a protein he discovered eight years ago while a U-M graduate student.

“SH2-B is an intracellular signaling molecule that increases the body’s sensitivity to leptin, a hormone which regulates energy balance and body weight in humans and animals,” says Rui.

SH2-B interacts with JAK2 – a key signalling protein that mediates how cells respond to a variety of hormones, including leptin.

One of several hormones produced by fat tissue, leptin’s role is to keep the brain informed about the amount and availability of nutrients stored in body fat.

“Leptin sends a powerful signal to the brain saying: we have a surplus, reduce feeding and increase energy expenditures,” says Rui.

Leptin sensitivity is determined by a balance between positive and negative regulators, he adds. But previously scientists only knew the negative regulators.

“Now we’ve demonstrated that SH2-B is the first example of an intracellular signalling protein with a positive, rather than negative, effect on leptin signal transduction, he adds.

His research with mice that lack the SH2-B gene, and so can not make SH2-B protein, indicates that its presence is required to maintain normal energy metabolism and body weight in mice.

When leptin travels through the bloodstream and reaches the hypothalamus, two types of neurons respond to its signal. Orexigenic neurons produce neuropeptides that promote eating. Neuropeptides produced by anorexigenic neurons, on the other hand, inhibit eating.

In order to send its “stop eating” signal, leptin increases production of anorexigenic neuropeptides, while it inhibits production of orexigenic neuropeptides.

When Rui’s research team measured neuropeptides produced by hypothalamic neurons in mice without SH2-B and compared results to those from normal mice, they found major differences. “Even though blood levels of leptin in SH2-B null mice were dramatically higher than in normal littermate controls, orexigenic neuropeptide levels were twice as high as in normal mice,” says Decheng Ren, U-M research fellow and first author of the study. Deleting SH2-B impairs the sensitivity of these hypothalamic neurons to leptin, and may contribute to over-eating and obesity in SH2-B null mice, he adds. Full findings for the results on SH2-B and how it regulates the brain’s sensitivity to leptin are published in the August 2005 issue of Cell Metabolism.





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If the mice were humans, the standard answer would be that they just need to control their food portions, limit their fat intake and exercise!

5 bucks says that this protein is controlled by insulin, more specifically when insulin is high it is suppressed. How else do you explain the fact that many "ravenous obese" find themselves able to control their "gluttony" the moment they get insulin levels down (LC diet)?

You know they keep looking for these hormones that affect metabolism to try to make drugs. As far as weight is concerned, insulin is the the conductor of an orchestra. Trying to change metabolism ignoring it and focusing on the things ultimately controlled by it is a mistake.

Once again, we see scientific research distorted by the search for the designer molecule. SH2-B does whatever it does because it interacts with a bunch of other proteins, enzymes, and hormones in a metabolic pathway. When this metabolic pathway is out of kilter, one result can be obesity. The point of medical research should be to answer the question: How do we make this metabolic pathway whole again so it doesn't lead to obesity.

But that's not what has happened. These researchers ascribe to the disease management model of healthcare in which obesity is a disease requiring a treatment. The only point of isolating one element of a metabolic pathway as the cause of a disease is to create a designer molecule that would impede or stimulate that element, since that's what designer molecules do. That designer molecule is worth billions to whatever drug company first patents it. The corporate shils at the NIH will ram through approval and take their consulting fees. And years later, there will be a bunch of law suits over the secondary effects of deforming this metabolic pathway.

They could have isolated almost any other element of that metabolic pathway that they could bioengineer some mouse not to have and have gotten similar results.

I suspect that Wooo is right and that insulin control is the key to making this pathway whole again. I like her metaphor about the orchestra. What she's calling the orchestra, I'm identifying as the metabolic pathway.

The point is that there are two competing narratives: the disease management/ lipid hypothesis story, supported by the medical-pharmaceutical-health insurance complex and the mainstream scientific and popular media, and the metabolic pathway management/insulin control story, supported by Wooo, myself, and everyone else on this board. Guess which narrative is currently winning?