Effects Of Liraglutide On Endoplasmic Reticulum Stress Of The High-fat-diet Induced Obese Rats

BackgroundThe numbers of people who suffer from overweight and obese increase year byyear.Obesity has attracted the attention of scholars caused by a variety of metabolicdisorders, but the loss of weight seems to be a worldwide problem, because that therate of obesity-related diseases such as metabolic syndrome, type2diabetes, coronaryheart disease, hyperlipidemia hyperlipidemia, non-alcoholic fatty liver diseasesincreases sharply these years.However,what cause so many obesity and metabolicdiseases? It is believed that obesity is related to cell stress and activation ofinflammatory signaling pathways in liver, pancreas, cardiovascular, adipose tissue, ofwhich endoplasmic reticulum stress plays an important role. Liraglutide could loseweight has become a consensus,and there are so many researchs about whosemechanism of weight loss,such as reducing feeding doctrine and slowing gastricsquirm etc, but its impact on endoplasmic reticulum stress of mitigating weight hasnot been reported.ObjectiveTo investigate glucagon-like peptide-1(GLP-1) receptor agonist Liraglutide onbody weight and endoplasmic reticulum stress within adipose tissue of high-fat dietinduced obese rats. Methods48male SD rats were randomly divided into two groups, including a normal fat(NC) group (NC, n=8) and a high fat (HF) group (HF, n=40). At the end of8thweek, the body weights were measured and rats of HF group with body weights morethanx+1.96s of NF group were chosen as high fat diet induced obesity (DIO) group,and they are subdivided into two groups, including a Liraglutide-treated (DIOLira)subgroup and a saline-treated (DIOsaline) subgroup. In the next8weeks, rats in DIO-liragroup received100μg/kg liraglutide (100μg/ml intraperitoneal injection, ip) twice aday, DIO-saline and NC group received the same volume of saline (ip) at the sametime each day, and both subgroups were continuouely fed with high-fat diet. At theend of the16th week, all groups were sacrificed. Each rat of three groups wasweighted, quickly removed and the adipose tissue around the kidney and epididymiswas weighed and finally the expressions of PERK、IRE1-α、CHOP at mRNA andGRP78at protein levels within adipose tissue were measured.ResultsAfter8weeks of diet intervention, seventeen rats of HF group were chosen asDIO rats, and their body weights were significantly higher compared to NF rats(P＜0.01). At the end of16th week, body weight combined with ratio of fat/body weightand adipose tissue and the expression levels of PERK、IRE1-α、CHOP at mRNA andGRP78at protein levels in DIOsalinerats was significantly increased compared to NCand DIOLirarats(P＜0.01). Compared to NC rats, body weight, ratio of fat/bodyweight and the expression of PERK、IRE1-α、CHOP at mRNA and GRP78at proteinlevels in DIOLirarats were significantly increased (P＜0.01).Conclusion1High-fat diet can induce rats obese.2High-fat diet can induce obesity and endoplasmic reticulum stress,by increasing stress markers factor PERK and expression of IRE1-α, CHOPmRNA, GRP78protein within the adipose tissue.3. Liraglutide acts like GLP-1may ameliorate the body weight gain in high-fat dietinduced obese rats, and significantly decrease endoplasmic reticulum stress in theadipose tissue,by decreasing PERK, IRE1-α CHOP mRNA and protein expressionof GRP78.