Effects of Macronutrients on the In Vitro Production of ClpB, a Bacterial Mimetic Protein of α-MSH and Its Possible Role in Satiety Signaling
Résumé
Gut microbiota can influence the feeding behavior of the host, but the underlying
mechanisms are unknown. Recently, caseinolytic protease B (ClpB), a disaggregation chaperon
protein of Escherichia coli, was identified as a conformational mimetic of α-melanocyte-stimulating
hormone (α-MSH), an anorexigenic neuropeptide. Importantly, ClpB was necessary for E. coli to have
an anorexigenic effect in mice, suggesting that it may participate in satiety signaling. To explore this
further, we determined the short-term (2 h) effects of three macronutrients: protein (bovine serum
albumin), carbohydrate (D-fructose) and fat (oleic acid), on the production of ClpB by E. coli and
analyzed whether ClpB can stimulate the secretion of the intestinal satiety hormone, peptide YY (PYY).
Isocaloric amounts of all three macronutrients added to a continuous culture of E. coli increased ClpB
immunoreactivity. However, to increase the levels of ClpB mRNA and ClpB protein in bacteria and
supernatants, supplementation with protein was required. A nanomolar concentration of recombinant
E. coli ClpB dose-dependently stimulated PYY secretion from the primary cell cultures of rat intestinal
mucosa. Total proteins extracted from E. coli but not from ClpB-deficient E. coli strains also tended to
increase PYY secretion. These data support a possible link between E. coli ClpB and protein-induced
satiety signaling in the gut.