内科学
内分泌学
葡萄糖稳态
生物
糖异生
肠道菌群
胰高血糖素样肽-1
丙酸盐
碳水化合物代谢
能量稳态
2型糖尿病
基因敲除
胰岛素
新陈代谢
糖尿病
生物化学
胰岛素抵抗
基因
医学
肥胖
作者
Yanan Wang,Mengjie Li,Jingya Guo,Seong‐Gook Kang,Kunlun Huang,Tao Tong
摘要
Abstract Olfr78, which is a novel receptor for short‐chain fatty acid (SCFA) acetate and propionate, plays essential roles in some cellular processes. The present study aimed to investigate the role of olfr78 in regulating energy metabolism and delineate the underlying mechanisms using olfr78 −/− mice. Deletion of olfr78 did not influence the adiposity of mice fed either normal chow or a high‐fat diet (HFD). However, olfr78 −/− mice exhibited glucometabolic dysfunction, as evidenced by increased fasting blood glucose levels, decreased serum insulin levels, and impaired oral glucose tolerance under HFD feeding. When compared to wild‐type (WT) mice, olfr78 deficiency enhanced HFD‐induced gluconeogenesis and increased the mRNA expression of key gluconeogenic genes in the liver and kidney. Quantitative real‐time PCR results revealed that olfr78 expression was higher in the colon compared with other tissues in WT mice. Analysis of the gut microbiota in the feces of olfr78 −/− mice using 16S rRNA gene sequencing revealed altered relative abundances of some representative SCFAs producers along with decreased levels of SCFAs, including propionic, isobutyric, 2‐methylbutyric, valeric, isovaleric, and 4‐methylvaleric acids. Importantly, mice lacking olfr78 had low circulating levels of glucagon‐like peptide 1 (GLP‐1). In the STC‐1 enteroendocrine cell line, propionate and acetate induced the secretion of the gut hormone GLP‐1, and this effect was partially abolished by olfr78 siRNA‐mediated knockdown. Together, these results suggest a previously undescribed, specific regulatory role for gut olfr78 in glucose homeostasis and highlight olfr78 as a potential target for diabetes treatment.
科研通智能强力驱动
Strongly Powered by AbleSci AI