An orally active plant Rubisco-derived peptide increases neuronal leptin responsiveness

• Published in: Scientific reports Vol. 12; no. 1; pp. 8599 - 11
• Main Authors: Kaneko, Kentaro, Takekuma, Yukihiro, Goto, Tsuyoshi, Ohinata, Kousaku
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 21.05.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/45/611; 692/699/1702/393; Body weight; Body weight gain; Brain slice preparation; Food intake; Forskolin; High fat diet; Humanities and Social Sciences; Hypothalamus; Inflammation; Interleukin 1; Leaves; Leptin; multidisciplinary; Obesity; Oral administration; Palmitic acid; Pancreatin; Pepsin; Peptides; Phosphorylation; Rap1 protein; Ribulose-bisphosphate carboxylase; Science; Science (multidisciplinary); Stat3 protein
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-12595-6

Nutrient excess, such as the intake of a high-fat diet, reduces hypothalamic responses to exogenously administered leptin and induces dietary obesity; however, orally active components that attenuate neural leptin dysregulation have yet to be identified. We herein demonstrated that YHIEPV, derived from the pepsin-pancreatin digestion of the green leaf protein Rubisco, increased the leptin-induced phosphorylation of STAT3 in ex vivo hypothalamic slice cultures. We also showed that YHIEPV mitigated palmitic acid-induced decreases in leptin responsiveness. Furthermore, orally administered YHIEPV promoted leptin-induced reductions in body weight and food intake in obese mice. In addition, dietary-induced body weight gain was significantly less in mice orally or centrally administered YHIEPV daily than in saline-control mice. Cellular leptin sensitivity and the levels of proinflammatory-related factors, such as IL1β and Socs-3 , in the hypothalamus of obese mice were also restored by YHIEPV. YHIEPV blocked cellular leptin resistance induced by forskolin, which activates Epac-Rap1 signaling, and reduced the level of the GTP-bound active form of Rap1 in the brains of obese mice. Collectively, the present results demonstrated that the orally active peptide YHIEPV derived from a major green leaf protein increased neural leptin responsiveness and reduced body weight gain in mice with dietary obesity.