Liver fat could cause insulin resistance

Scientists believe that the liver could hold the key to preventing and treating type 2 diabetes. With 95 percent of diabetics diagnosed with type 2, it’s a lot more prevalent than type 1. All current therapies for type 2 diabetes primarily aim to decrease blood glucose. It’s treating a symptom, much like decreasing the fever in a case of the flu. According to Benjamin Renquist, associate professor of Arizona College of Agriculture and Life Sciences, we need another breakthrough.

Renquist, along with other researchers, is the author of two newly published papers in Cell Reports that outline a new target for type 2 diabetes treatment. He’s spent the past nine years studying the correlation between obesity, fatty liver disease, and diabetes, with focus on how the liver affects insulin sensitivity.

Fat in the liver increased with obesity, and so did the incidence of type 2 diabetes. It suggested that the fat in the liver might be causing type 2 diabetes, but how liver fat could increase insulin resistance or cause oversecretion of insulin in the pancreas remained a mystery.

The scientists concentrated on how the fatty liver released neurotransmitters to communicate with the brain and influence the metabolic changes seen in obesity and diabetes. They found that fat in the liver increased the secretion of inhibitory GABA (gamma-aminobutyric acid). It decreases nerve activity and firing to the brain. To determine if the increased GABA synthesis was causing insulin resistance, it was pharmacologically inhibited in animals. Insulin sensitivity was restored within days, and over a longer time, food intake decreased, and weight loss occurred.

Researchers translated the findings to humans by showing that in people with insulin resistance, the liver more highly expressed genes involved in GABA production and release. The findings make up the foundation for a clinical trial of an FDA-approved inhibitor of GABA transaminase that lowers GABA levels. The hope is that it will improve insulin sensitivity in people with obesity.

While we’re still years away from a pharmacological solution, the magnitude of the obesity crisis makes these promising findings a first step that could affect health outcomes in the future.