Exogenous IGF-1 alleviates depression-like behavior and hippocampal mitochondrial dysfunction in high-fat diet mice

Some evidence suggests that depression is more common in obese patients. This fact gives us a hint that obesity might be a promoter of depression, though a

IGF-1 alleviated depression-like behaviors and mitochondrial dysfunction through the activation of CREB/PGC-1α signal pathway in HFD mice.

C57BL/6 J mice were fed with HFD to establish a model of obesity. Then, the animals were separately or simultaneously treated with PEG-IGF-1, 666-15 (CREB blocker) and SR-18292 (PGC-1α blocker). After that, depression-like behaviors were assessed using sucrose preference test and tail suspension test. In hippocampus, respiratory control ratio, ATP generation and red/green fluorescence ratio were adopted to reveal mitochondrial function. Also in hippocampus, expressions of p-CREB and PGC-1α were measured using western blotting.

HFD mice showed depression-like behaviors compared with control mice. Such diet also caused mitochondrial dysfunction and inhibition of CREB/PGC-1α signal pathway in hippocampus of these animals. After PEG-IGF-1 intervention, all the abnormalities mentioned above can be partly reversed. After 666-15 or SR-18292 treatment, such protective effect of PEG-IGF-1 can be attenuated, and the mice suffered from the re-deterioration of behavioral and mitochondrial abnormalities in hippocampus.