Nonalcoholic fatty liver disease (NAFLD) is a common complication of obesity and is
associated with an increased risk of developing type 2 diabetes. The hallmark feature of
NAFLD is an increase in intrahepatic triglyceride (IHTG) content. Data from studies conducted
in rodent models suggest increased IHTG content can alter hepatic vagal afferent nerve (HVAN)
activity. In rodent models of obesity and NAFLD, HVAN activity is reduced leading to impaired
insulin sensitivity and glucose control. The reduction in HVAN activity is likely due to
increased hepatic release of GABA, an inhibitory neurotransmitter, attributable to increased
expression of GABA-Transaminase (GABA-T). Pharmacological inhibition of GABA-T in obese mice
by treatment with vigabatrin, an irreversible inhibitor of GABA-T improves glucose tolerance
and reduces hyperinsulinemia, hyperglycemia, and insulin resistance. It is not known if
vigabatrin can also improve metabolic function in people. We propose to conduct a randomized
clinical controlled trial to determine the effect of vigabatrin on insulin sensitivity and
oral glucose tolerance in adults with obesity and NAFLD.