Berberine(BBR)was reported to preserve the colon function in GLP-1 secretion in obese rodents through the butyrate-GPR43 pathway. However, the mechanism remains largely unknown except the pathway. Here, we tested BBR activity in the inhibition of clone epithelial necrosis in diet-induced obese mice. BBR was administrated in DIO mice through dietary supplementation for 8 weeks. Energy balance, insulin sensitivity and intestine mucosal function were monitored. Mitochondria were examined in the large intestine epithelial cells for structure and function to understand cell death. Mitochondrial structure was examined under the transmission electron microscopy and the function was determined using Seahorse XF24. Gut microflora was examined by Miseq sequencing and the fecal short chain fatty acids (SCFAs) were examined using gas chromatograph (GC). An increase in epithelial necrosis was observed in the colon mucosa together with a reduction in GLP-1 secretion and expression in DIO mice. Cristae loss and membrane rupture were observed in the mitochondrial structure of the colon epithelial cells. A disbalance of mitochondrial complexes was observed with an elevation in the complex I activity, and a fall in the complex II and IV activities. The abundance of short chain fatty acids were decreased along with the dysbiosis in the DIO mice. All of those alterations were corrected in DIO mice together with glucose disorder by the BBR treatment. The data suggest that BBR may protect the colon epithelial cells from necrosis in DIO mice to preserve GLP-1 secretion function. The effect was mediated by restoration of mitochondrial function from the disbalance among the complex I, II and IV. The direct and indirect effects of BBR are discussed.
J. Ye: None. J. Le: None. Y. Sun: None.