Regulation of microbiota-GLP1 axis by sennoside A in diet-induced obese mice.
10.1016/j.apsb.2019.01.014
- Author:
Jiamei LE
1
;
Xiaoying ZHANG
2
;
Weiping JIA
3
;
Yong ZHANG
4
;
Juntao LUO
2
;
Yongning SUN
5
;
Jianping YE
2
Author Information
1. Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China.
2. Central Laboratory, Shanghai Jiaotong University Affiliated Sixth People׳s Hospital East, Shanghai 201306, China.
3. Diabetes Institute, Shanghai Jiaotong University Affiliated Sixth People׳s Hospital, Shanghai 200233, China.
4. Antioxidant and Gene Regulation Laboratory, Pennington Biomedical Research Center, LSU, Baton Rouge, LA 70808 USA.
5. Department of Traditional Chinese Medicine, Shanghai Jiaotong University Affiliated Sixth People׳s Hospital, Shanghai 200233, China.
- Publication Type:Journal Article
- Keywords:
GLP1;
Gut microbiota;
Insulin sensitivity;
Mitochondria;
Sennoside A;
Short chain fatty acids
- From:
Acta Pharmaceutica Sinica B
2019;9(4):758-768
- CountryChina
- Language:English
-
Abstract:
Sennoside A (SA) is a bioactive component of Chinese herbal medicines with an activity of irritant laxative, which is often used in the treatment of constipation and obesity. However, its activity remains unknown in the regulation of insulin sensitivity. In this study, the impact of SA on insulin sensitivity was tested in high fat diet (HFD)-induced obese mice through dietary supplementation. At a dosage of 30 mg/kg/day, SA improved insulin sensitivity in the mice after 8-week treatment as indicated by HOMA-IR (homeostatic model assessment for insulin resistance) and glucose tolerance test (GTT). SA restored plasma level of glucagon-like peptide 1 (GLP1) by 90% and mRNA expression of by 80% in the large intestine of HFD mice. In the mechanism, SA restored the gut microbiota profile, short chain fatty acids (SCFAs), and mucosal structure in the colon. A mitochondrial stress was observed in the enterocytes of HFD mice with ATP elevation, structural damage, and complex dysfunction. The mitochondrial response was induced in enterocytes by the dietary fat as the same responses were induced by palmitic acid in the cell culture. The mitochondrial response was inhibited in HFD mice by SA treatment. These data suggest that SA may restore the function of microbiota-GLP1 axis to improve glucose metabolism in the obese mice.
