Otago University. New-Zealand: Using an antioxidant to reverse inflammation in the brain caused by a
high-fat diet greatly improves symptoms related to obesity and type II
diabetes, a new University of Otago-led study suggests.
The research, which appears in the leading international journal Diabetes, was led by Dr Alex Tups of the University’s Centre for Neuroendocrinology and Department of Physiology.
Dr Tups and an international team investigated whether directly
stopping inflammatory processes in the brain’s hypothalamus could help
lower blood sugar levels and reduce insulin resistance.
In their research the team blocked a particular inflammatory
signalling pathway (IKKβ/NF-κB) in the brains of obese mice. The
researchers studied both mice that were obese due to a deficiency in the
satiety hormone leptin and others due to a high-fat diet.
The scientists administered butein to the mice to block the
signalling pathway, which is involved in the body’s inflammatory immune
responses. Butein is a flavonoid derived from plants traditionally used
in Chinese herbal medicine.
Dr Tups says the team found that administering butein either directly
into the brain or orally greatly improved glucose tolerance and brain
insulin signalling in both types of obese mice.
“We also showed that this profound effect was dose-dependent with
better glucose tolerance achieved through higher doses of butein,” Dr
Tups says.
The improved glucose tolerance of high-fat diet mice treated with the
antioxidant was 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.
This gene therapy resulted in high-fat diet mice having a reduced
body weight, building up less fat, expending more energy, and showing
evidence of improved leptin-signalling.
Dr Tups says the study adds to growing body of evidence that a diet
high in saturated fats activates 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 says.
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 says.