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Circadian GLP-1 secretion in mice is dependent on the intestinal microbiome for maintenance of diurnal metabolic homeostasis
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posted on 2020-09-14, 21:41 authored by Ada AdminAda Admin, Sarah E. Martchenko, Alexandre Martchenko, Brian J. Cox, Kendra Naismith, Alison Waller, Patrick Gurges, Maegan E. Sweeney, Dana J. Philpott, Patricia L. BrubakerThe incretin, glucagon-like peptide-1 (GLP-1), is
secreted by the intestinal L-cell upon nutrient ingestion. GLP-1 also exhibits
a circadian rhythm, with highest release at the onset of the feeding period.
Similarly, microbial composition and function exhibit circadian rhythmicity with
fasting-feeding. The circadian pattern of GLP-1 release was found to be
dependent upon the oral route of glucose administration and was necessary for
the rhythmic release of insulin and diurnal glycemic control, in normal male
and female mice. In mice fed a western (high-fat/high-sucrose) diet for 16wk,
GLP-1 secretion was markedly increased but arrhythmic over the 24hr day,
whereas levels of the other incretin, glucose-dependent insulinotrophic
polypeptide were not as profoundly affected. Furthermore, the changes in GLP-1
secretion were shown to be essential for the maintenance of normoglycemia in
this obesogenic environment. Analysis of the primary L-cell transcriptome, as
well as of the intestinal microbiome, also demonstrated time-of-day- and
diet-dependent changes paralleling GLP-1 secretion. Finally, studies in antibiotic-induced
microbial-depletion, and in germ-free mice with and without fecal microbial
transfer provided evidence for a role of the microbiome in diurnal GLP-1
release. In combination, these findings establish a key role for
microbiome-dependent circadian GLP-1 secretion in the maintenance of 24-hour
metabolic homeostasis.