グレリンファミリーペプチドによる食欲・消化管運動調節(シンポジウム : 心身医学における研究と診療の最先端,2007年,第48回日本心身医学会総会(福岡))  [in Japanese] Feeding and Gastrointestinal Motility : Regulation by Ghrelin Gene Products(Symposium : Frontiers Research and Practice in Psychosomatic Medicine)  [in Japanese]

脳腸ペプチドは食欲・体重調節に重要な役割を有することが知られているが,摂食行動と密接に関わる消化管機能の調節にも深く関わっている.グレリンは胃から見出された強力な食欲促進ペプチドであり,視床下部に存在する神経ペプチドY(neuropeptide Y ; NPY)やアグーチ関連ペプチド(agouti-related peptide ; AgRP)を介して,食欲や消化管運動に促進性の影響を及ぼす.グレリンにはアシル化された分子型と,アシル基のない分子型(デスアシルグレリン)が存在し,また近年,同じグレリン遺伝子から産生される消化管ペプチドであるオベスタチンが見出された.アシルグレリンは摂食や消化管運動に促進作用を有するのに対し,デスアシルグレリンは促進,抑制両方向に作用,またオベスタチンは抑制もしくは作用なしと報告されている.本稿では,グレリンファミリーペプチドによる食欲・消化管運動調節を概括し,議論の多いこの点を含めて述べる.

Gastrointestinal (GI) hormones are well known to be important regulators not only in GI functions but also in feeding behavior. Ghrelin, a motilin-related family of regulatory peptide from the stomach, is the recent addition of this list, which has a charactelistic n-octanoylated serine at position 3. In addition to its ability to stimulate growth hormone (GH) secretion, ghrelin increases appetite and gastric motility/emptying and induces a positive energy balance leading to body weight gain. Ghrelin is a complementary, yet antagonistic, signal to leptin reflecting acute and chronic changes in energy balance, the effects of which are mediated by hypothalamic neuropeptide Y (NPY) and agouti-related peptide (AgRP). Ghrelin induces the fasted pattern of gastroduodenal motility (phase III or hunger contractions) , and the ghrelin-NPY axis is involved in the physiological occurrence of the interdigestive phase III contractions in rodents. On the other hand, desacyl form of ghrelin that accounts for approximately 90% of total circulating ghrelin, decreases food intake and gastric emptying, and disrupts the fasted pattern of gastric motility. Obestatin, a recently identified ghrelin gene product, may also act inhibitory in appetite and GI motility regulation although much more controversial than ghrelin. The findings suggest that ghrelin gene products may differently regulate appetite and gastrointestinal motility through different endocrine/neural pathways along the gut-brain axis.