Anti-ghrelin immunoglobulins modulate ghrelin stability and its orexigenic effect in obese mice and humans.

2014 Fiscal Year Final Research Report

• Project/Area Number: 25670355
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General internal medicine(including psychosomatic medicine)
• Research Institution: Kagoshima University
• Principal Investigator: INUI Akio 鹿児島大学, 医歯(薬)学総合研究科, 教授 (80168418)
• Co-Investigator(Renkei-kenkyūsha): UEZONO Yasuhito 独立行政法人国立がん研究センター, がん患者病態生理研究分野, 分野長 (20213340) ; ITO Yuji 鹿児島大学, 理工学部, 教授 (60223195)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 肥満症 / グレリン / 自己抗体

Outline of Final Research Achievements

Obese individuals often have increased appetite despite normal plasma levels of the main orexigenic hormone ghrelin. Here we show that ghrelin degradation in the plasma is inhibited by ghrelin-reactive IgG immunoglobulins, which display increased binding affinity to ghrelin in obese patients and mice. Co-administration of ghrelin together with IgG from obese individuals, but not with IgG from anorectic or control patients, increases food intake in rats. Similarly, chronic injections of ghrelin together with IgG from ob/ob mice increase food intake, meal frequency and total lean body mass of mice. These data reveal that in both obese humans and mice, IgG with increased affinity for ghrelin enhances ghrelin's orexigenic effect, which may contribute to increased appetite and overeating. We are now performing the isolation of each ghrelin-reactive immunoglobulins with difficulty because of the small MW of ghrelin.

Free Research Field

心身医学、心療内科学