Insulin Signaling in the Brain Controls Fat Metabolism

By: Almas Eftekhari

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One of the hallmark defects of type 2 diabetes is resistance to insulin produced in the pancreas. Yet, scientists at the Mount Sinai School of Medicine have made a novel discovery that another organ – the brain – plays a more pivotal role in the disease than formerly realized. They found that insulin inside the hypothalamus region of the brain is involved in controlling the function of fat tissue – a key component in energy and metabolic pathways relevant to type 2 diabetes.

During conditions of demanding energy needs, like starvation or exercise, fat tissue breaks down and releases fatty acids for the body to use.  In type 2 diabetes, this process (called lipolysis) is unrestrained and occurs at times when additional energy is not needed, such as after eating. The excessive level of fatty acids circulates in the body and creates a harmful saturation of fat in vital organs and tissues. This contributes to insulin resistance and can accelerate diabetes.

The research team, led by American Diabetes Association-funded researcher Christoph Buettner, MD., PhD., is the first to show that brain insulin signaling is a major regulator of fat metabolism, and that impairment of brain insulin can lead to the uncontrolled breakdown of fat tissue. After infusing insulin into the brains of rats, the scientists observed lipolysis-control and normal fat and sugar metabolism. Conversely, rodents with deficient brain insulin activity exhibited unrestrained lipolysis. 

 “When brain insulin function is impaired, the release of fatty acids is increased. This induces inflammation, which can further worsen insulin resistance, the core defect in type 2 diabetes. Therefore, impaired brain insulin signaling can start a vicious cycle since inflammation can impair brain insulin signaling,” said Dr. Buettner.  Results of the study are published in the February 2011 issue of Cell Metabolism

Furthermore, Dr. Buettner’s Research Award from the ADA has enabled him to explore factors that may hinder brain insulin function. In a separate study published in the April 2011 issue of Diabetes, his team observed that overfeeding rats causes insulin resistance in the brain and thus impairs the ability of brain insulin to suppress lipolysis.

“Overeating, a major sin of our time, leads to the loss of adequate control of metabolism by the brain. The overabundance of nutrients leaves the brain in a state of paralysis where hormones like insulin lose their regulatory function. I believe that in coming years, we will elucidate the defects that make the brain unresponsive to the regulatory action of hormones and nutrients,” he concluded.

Scherer T, O'Hare J, Diggs-Andrews K, Schweiger M, Cheng B, Lindtner C, Zielinski E, Su K, Dighe S, Milsom T, Puchowicz M, Scheja L, Zechner R, Fisher S, Previs S, Buettner C. Brain insulin controls adipose tissue function. Cell Metabolism; 2011 February; 13(2): 183-194.

O'Hare J, Zielinski E, Cheng B, Scherer T, Buettner C. Central endocannabinoid signaling regulates hepatic glucose production and systemic lipolysis. Diabetes; 2011 April; 60(4):1055-62.