The research, which appears in the journal Diabetes, was led by Otago endocrinologist Dr Alex Tups, and concludes that more investigation is needed into some natural compounds that can block inflammation of the brain.
Tups led an international team of scientists to study if stopping inflammatory processes in the brain’s hypothalamus directly could help lower blood sugar levels and reduce insulin resistance.
Derived from traditional Chinese medicine
The team blocked a particular inflammatory signalling pathway (IKKβ/NF-κB) in the brains of obese mice. The obese mice either had a satiety hormone deficiency, or were being fed a high-fat.
Butein, a flavonoid derived from plants traditionally used in Chinese herbal medicine, can block the signalling pathway that triggers the body’s inflammatory immune response.
Tups said the team found that administering butein, which can be given orally or directly in the brain, greatly improved glucose tolerance and brain insulin signalling in both groups of obese mice.
“We also showed that this profound effect was dose-dependent with better glucose tolerance achieved through higher doses of butein,” said Tups.
The mice on a high-fat diet showed improved glucose tolerance such that no difference was noticeable between them and low fat-diet mice that had not received butein.
To confirm that activation of the IKKβ/NF-κB pathway plays a central role in metabolic obesity symptoms, the researchers also used a gene therapy technique to inhibit it in neurons in the hypothalamus.
Reversing inflammation is the key
This gene therapy resulted in mice with the high-fat diet having a reduced body weight, building up less fat, expending more energy, and showing evidence of improved leptin-signalling.
Tups said the study added to a growing body of evidence that a diet high in saturated fats could activate a cascade of inflammatory processes in the brain which impair leptin and insulin signalling, leading to obesity and type II diabetes.
“Our findings strongly support this idea and we also show that reversing this inflammation promotes a return towards normal metabolic functioning,” he said.
The research suggests that butein and other natural compounds that block inflammation in the brain should be vigorously investigated as novel anti-diabetic treatments, he said.