Gut microbiota impairs insulin clearance in obese mice
- Resource Type
- Authors
- Brandyn D. Henriksbo; Michael Schwab; Cassandra Y. Chen; Kevin P. Foley; Roxanne Plante; Brittany M. Duggan; Jonathan D. Schertzer; Nicole G. Barra; Joseph F. Cavallari; André Marette; Michael Huang; Trevor C. Lau; Fernando F. Anhê; Soumaya Zlitni
- Source
- Molecular Metabolism, Vol 42, Iss, Pp 101067-(2020)
- Subject
- 0301 basic medicine
Blood Glucose
Male
lcsh:Internal medicine
medicine.medical_specialty
medicine.drug_class
medicine.medical_treatment
Antibiotics
Mice, Obese
030209 endocrinology & metabolism
Type 2 diabetes
Gut flora
Diet, High-Fat
03 medical and health sciences
Feces
Mice
0302 clinical medicine
Insulin resistance
Diabetes mellitus
Internal medicine
Hyperinsulinism
RNA, Ribosomal, 16S
medicine
Hyperinsulinemia
Animals
Insulin
Obesity
lcsh:RC31-1245
Molecular Biology
2. Zero hunger
biology
business.industry
Microbiota
Diabetes
Cell Biology
medicine.disease
biology.organism_classification
3. Good health
Gastrointestinal Microbiome
Mice, Inbred C57BL
030104 developmental biology
Endocrinology
Glucose
Liver
Insulin Resistance
business
- Language
- ISSN
- 2212-8778
Objective Hyperinsulinemia can be both a cause and consequence of obesity and insulin resistance. Hyperinsulinemia can result from increased insulin secretion and/or reduced insulin clearance. While many studies have focused on mechanisms triggering insulin secretion during obesity, the triggers for changes in insulin clearance during obesity are less defined. In this study, we investigated the role of the microbiota in regulating insulin clearance during diet-induced obesity. Methods Blood glucose and insulin clearance were tested in conventional male mice treated with antibiotics and germ-free mice colonized with microbes from mice that were fed a control (chow) diet or an obesogenic high-fat diet (HFD). The composition of the fecal microbiota was analyzed using 16S rRNA sequencing. Results Short-term HFD feeding and aging did not alter insulin clearance in the mice. Oral antibiotics mitigated impaired blood insulin clearance in the mice fed an HFD for 12 weeks or longer. Germ-free mice colonized with microbes from HFD-fed donor mice had impaired insulin but not C-peptide clearance. Microbe-transmissible insulin clearance impairment was only observed in germ-free mice after more than 6 weeks post-colonization upon HFD feeding. Five bacterial taxa predicted >90% of the variance in insulin clearance. Mechanistically, impaired insulin clearance was associated with lower levels of hepatic Ceacam-1 but increased liver and skeletal muscle insulin-degrading enzyme (IDE) activity. Conclusions Gut microbes regulate insulin clearance during diet-induced obesity. A small cluster of microbes or their metabolites may be targeted for mitigating defects in insulin clearance and hyperinsulinemia during the progression of obesity and type 2 diabetes.