An indoline-derived compound that markedly reduces mouse body weight.

摘要: We describe how a single intraperitoneal injection of an indoline-derived drug (SN 28127) reduced mouse body weight (25–45% loss) and adipose tissue mass (∼75%). The reductions in peaked at ∼21–28 days post were maintained throughout the study (160 days). mice ate as much vehicle-treated control mice. A more potent SN 28127 analog 29220) reversed high-fat diet-induced obesity type 2 diabetes C57BL/6J on diet. Insulin induced sustained reduction blood glucose fasted 29220-treated compared with All drug-treated exhibited transient increase water intake from ∼10 that lasted for ∼70 days. Following 3H-labeled 29220, radioactivity accumulated within 4 h liver, bile duct ileum little detected brain; 1–2 days, most was found pancreas, spleen, duct, stomach, kidneys white tissue. High levels urine collected 29220 but not ∼60 injection, while fecal triacylglycerols cholesterol different between These data lead us to hypothesize hepatic system is primary target. Genes involved fatty acid synthesis (FASn, SCD1 PPARγ) appetite stimulation (AGRP) upregulated 160 treatment, indicative adaptation weight. drug-induced chronic toxicity leads mass. adapt this steady-state Understanding molecular mechanisms underlying these responses has potential identify novel targets prevention treatment obesity.