Orally administered δ opioid agonist peptide rubiscolin-6 stimulates food intake in aged mice with ghrelin resistance.

Abstract

It is known that a decline in food intake occurs with aging. In this study, we investigated changes in parameters associated with food intake in response to aging, and whether orexigenic peptides stimulated food intake after peripheral administration even in aged mice. Food intake and body weight of 27-month-old male C57BL/6N mice were lower than those of 15-month-old mice. Epididymal and mesenteric fat mass, blood glucose, triglyceride, and leptin levels were also decreased. Meanwhile, the hypothalamic mRNA expression of endogenous orexigenic peptides such as neuropeptide Y (NPY) and agouti-related protein, also called agouti-related peptide, was increased. Next, we tested responsiveness to exogenously administered orexigenic peptides coupled to NPY in aged as well as young mice. Orally administered rubiscolin-6, a δ opioid agonist hexapeptide derived from a major green leaf protein Rubisco, stimulated food intake in 27-month-old mice. In contrast, ghrelin was ineffective after intraperitoneal administration to aged mice, suggesting that the NPY system downstream of ghrelin but not δ opioid receptors might be impaired in aged mice. Orally administered rubiscolin-6 stimulates food intake in aged mice with ghrelin resistance.