METHODS AND COMPOSITIONS TO ALTER HEPATIC GABA RELEASE TO TREAT OBESITY-RELATED CONDITIONS

摘要

Methods and compositions for treating conditions caused by altered hepatic GABA production and release, including hyperinsulinemia, insulin resistance, type II diabetes, obesity, and obesity-related conditions. The present invention describes hepatic GABA as a hepatokine. The methods herein feature manipulating the expression and/or activity of specific GABA transporters, e.g., increasing expression of SLC6A12 and/or SLC6A13 genes or increasing activity of the proteins for which they encode, BGT1 and/or GAT2; or decreasing expression of SLC6A6 and SLC6A8 genes or increasing the activity of the proteins for which they encode, TauT and/or CRT, which can increase hepatic GABA re-uptake or decrease hepatic GABA release to improve insulin sensitivity and prevent hypertension.