Liver, diabetes and obesity
A new approach to the treatment of obesity and type II diabetes has been found
American scientists have found a link between obesity, fatty liver disease and diabetes. Researchers have determined how the liver interacts with the brain and affects the metabolic changes observed in obesity and diabetes. The authors believe that by acting on fat in the liver, it is possible to change insulin sensitivity. The results of the study are published in the journal Cell Reports (Geisler et al., A critical role of hepatic GABA in the metabolic dysfunction and hyperphagia of obesity).
Researchers from the University of Arizona, along with colleagues from Washington University School of Medicine in St. Louis, have been working for nine years to better understand the relationship between obesity, fatty liver disease and diabetes, in particular - how the liver affects insulin sensitivity.
"All modern therapeutic agents for the treatment of type 2 diabetes are primarily aimed at reducing blood glucose levels. So they treat the symptom. This is the same as treating the flu by lowering the temperature," the press release says. The words of the head of the study Dr. Benjamin Renquist (Benjamin Renquist), associate professor of the College of Agriculture and Life Sciences of the University.
It is known that obesity is one of the causes of type 2 diabetes, but with obesity, the amount of fat in the liver also increases.
"That is, as the amount of fat in the liver increases, the incidence of diabetes increases," Rehnquist notes. "But how fat in the liver causes insulin resistance or excessive insulin secretion by the pancreas remained a mystery."
To better understand how the liver interacts with the brain, the authors measured the levels of neurotransmitters secreted by obese laboratory mice and found that fat in the liver increases the release of the inhibitory neurotransmitter gamma-aminobutyric acid, or GABA.
"Then we identified the pathway by which the synthesis of GABA and the key enzyme responsible for the production of GABA in the liver – GABA transaminase - occurs," the scientist continues.
GABA is the main inhibitory neurotransmitter of the central nervous system of humans and other mammals, an amino acid that reduces nervous activity going from the brain to tissues and back, from tissues to the brain.
"GABA, which is produced by the liver, reduces the activity of nerves going from the liver to the brain. Thus, the fatty liver, producing GABA, reduces the active work of the brain. This decrease in arousal is felt by the central nervous system, which changes outgoing signals affecting glucose homeostasis," explains Dr. Rehnquist.
To determine whether increased GABA synthesis in the liver causes insulin resistance, scientists medicinally suppressed the production of GABA in the liver of mice with type 2 diabetes. This restored the sensitivity of the model animals to insulin within a few days. Longer-term inhibition of GABA transaminase resulted in reduced food intake and weight loss.
Additional studies have shown that in people with insulin resistance, the liver is more actively expressing genes involved in the production and release of GABA.
In the near future, the authors plan to start clinical trials, during which the use of a commercially available GABA transaminase inhibitor to improve insulin sensitivity in obese people will be studied.
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