Effects of Macronutrients on the In Vitro Production of ClpB, a Bacterial Mimetic Protein of α-MSH and Its Possible Role in Satiety Signaling

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 , was identified as a conformational mimetic of α-melanocyte-stimulating hormone (α-MSH), an anorexigenic neuropeptide. Importantly, ClpB was necessary for 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 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 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 ClpB dose-dependently stimulated PYY secretion from the primary cell cultures of rat intestinal mucosa. Total proteins extracted from but not from ClpB-deficient strains also tended to increase PYY secretion. These data support a possible link between ClpB and protein-induced satiety signaling in the gut.