Intestinal Epithelial CCL7 Protects Against High Fat Diet-induced Obesity And Hepatic Steatosis In Mice

Background and ObjectiveOur research group previously found that the intestinal epithelial CC chemokine ligand 7(CCL7)plays an important role in the development of toxin-induced acute liver damage.The detailed effects of intestinal epithelial CCL7 on chronic diseases,however,are still unclear.Here,we aimed to investigate the impact of intestinal epithelial CCL7 overexpression on high-fat diet(HFD)-induced obesity and steatohepatitis in mice.MethodFive-to six-week-old female CCL7tgIECmice and their WT littermates were used in the study.Intestinal epithelial CCL7 overexpression(CCL7tgIEC)mice and their wild type(WT)littermates were fed normal chow(D12450J,10kcal%fat,NC)or high fat diet(D12492,60 kcal%fat,HFD)for 16 weeks to induce obesity and non-alcoholic fatty liver disease(NAFLD),mice were housed in isolated cages in a 12h light/12h dark environment,animals had access to water and food ad libitum.We performed glucose tolerance test(GTT)and Insulin tolerance test(ITT)on NC and HFD mice at 13 and 14 weeks,respectively.After 16 weeks,experimental animal samples were collected for histological experiments,and DNA from mouse feces was extracted for 16S ribosomal RNA gene sequencing.ResultsResult 1:Intestinal epithelial CCL7 overexpression(CCL7tgIEC)mice that were fed the high-fat diet exhibited significant weight loss and gonadal fat,mesenteric fat,subcutaneous fat accumulation were reduced compared to HFD-fed WT mice,besides the concentrations of liver triglycerides and plasma cholesterol were significantly decreased in HFD-fed CCL7gIEC mce compared to the HFD-fed WT mice.HFD-induced glucose intolerance and insulin resistance were also significantly improved in CCL7tgIEC mice compared to WT,HFD-fed CCL7tgIEC mice displayed less hepatic lipid accumulation and lower expression of inflammatory factors than WT mice.Result 2:16S rRNA gene sequencing demonstrated that CCL7 overexpression in intestinal epithelial cells improved HFD-induced gut microbial dysbiosis by reduced the relative abundance of Desulfovibrionaceae compared to the HFD-fed WT mice.ConclusionIn conclusion,our study revealed that CCL7 overexpression in the intestinal epithelium protects mice against the progression of diet-induced obesity,steatohepatitis,and enteric dysbiosis.