14 DAY TRIAL // You can blame it on appetite, on depression, on addiction, but a team at the University of Michigan Medical School says that behind obesity there's just a protein in the brain's cells which plays a key role in the body's weight-regulating system, fat storage, sugar use and energy balance.
The research team showed that the SH2B1 protein regulates the activity of the metabolic signaling molecules leptin and insulin, and the way the organism metabolizes the energy from food.
The researchers even altered genetically the mice that presented a unique form of the SH2B1 protein in their brain cells. The investigators stopped the activity of this protein in the hypothalamus, the brain area used for eating, hunger, and energy balance.
The same team had already shown that mice lacking the gene for SH2B1 become obese, diabetic, and unable to stop eating: their brains cannot receive the signals sent by leptin and insulin that command to decrease of food intake and fat storage.
The team also investigated mice with SH2B1 only in brain cells, in normal or larger-than-normal quantities.
When restoring SH2B1 just in the brain, the metabolic disorders were completely gone, as the brain could receive leptin signals and continue the cycle that regulates eating. Moreover, the mice genetically engineered to make extra SH2B1 didn't develop obesity even after eating a high-fat diet. "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 Dr. Liangyou 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."
SH2B1 is located in the area just beneath the cell membrane and the nucleus, being able to bind to a variety of molecules called tyrosine kinases, including the ones that function as receptors for insulin and growth factors and JAK2, turned on each time a leptin molecule binds to a cell. Leptin is the messenger molecule which sends signals to the brain, such as "stop eating, that's enough", thus JAK2-SH2B1 link is important in stopping overeating.
Previously, the team had showed that SH2B1 stimulates the action and production of JAK2. SH2B1 was found in four different forms in adipose (fat) tissue, liver, heart, pancreas and muscle.
In fat cells, the lack of SH2B1 gene highly increased the fat storage, and the much larger fat cells led to a 2.5 times more body fat content than normal mice had. The mice that had their SH2B1 restored only in their brains did not present this and possessed in fact less body fat than normal mice. As these mice lacked SH2B1 in their fat cells, the researchers wanted to see why this happened. They discovered that SH2B1 provokes adipogenesis (turning embryonic cells into fat cells).
Through its research, the team wants to find better tactics for understanding what causes obesity and its consequences, including Type 2 diabetes, as well as useful knowledge on how to treat these conditions.