Three peptides, ghrelin, des-acyl ghrelin and obestatin are derived from a common prohormone, preproghrelin by posttranslational processing, originating from endocrine cells in the stomach. To examine the effects of t...Three peptides, ghrelin, des-acyl ghrelin and obestatin are derived from a common prohormone, preproghrelin by posttranslational processing, originating from endocrine cells in the stomach. To examine the effects of these peptides, we applied the manometric measurement of gastrointestinal motility in freely moving conscious rat models. Ghrelin exerts stimulatory effects on the motility of antrum and duodenum in both fed and fasted state of animals. Des-acyl ghrelin exerts inhibitory effects on the motility of antrum, but not on the motility of duodenum in the fasted state of animals. Obestatin exerts inhibitory effects on the motility of antrum and duodenum in the fed state, but not in the fasted state of animals. NPY Y2 or Y4 receptors in the brain may mediate the action of ghrelin, CRF type 2 receptors in the brain mediate the action of des-acy ghrelin, whereas CRF type 1 and type 2 receptors in the brain mediate the action of obestatin. Vagal afferent pathways might be involved in the action of ghrelin, but not involved in the action of des-acyl ghrelin, whereas vagal afferent pathways might be partially involved in the action of obestatin.展开更多
The cancer-associated anorexia-cachexia syndrome is observed in 80% of patients with advanced-stage cancer, and is one of the major obstacles in chemo- therapy. Ghrelin is a orexigenic hormone that has been proposed t...The cancer-associated anorexia-cachexia syndrome is observed in 80% of patients with advanced-stage cancer, and is one of the major obstacles in chemo- therapy. Ghrelin is a orexigenic hormone that has been proposed to prevent anorexia. Aim of the study was to determine whether the addition of the ghrelin agonist growth hormone releasing peptide 2 (GHRP-2) to cytotoxic therapy with 5-fluoruracil (5-FU) prevents the anorexia associated with chemotherapy in cancer cachectic mice. Thirty-three BALB/c female tumourbearing mice were randomized to receive a solution containing: (a) placebo; (b) GHRP-2; (c) 5-FU; or (d) 5-FU + GHRP-2. Ten BALB/c no tumour-bearing mice received placebo solution. Food intake and survival were checked. Six hours after the drug injection the cumulative food intake was signifi cantly increased in mice treated with the combination of 5-FU + GHRP-2 versus the 5-FU alone (P = 0.0096). On day 3, the cumulative food intake of mice treated with GHRP-2,5-FU and 5-FU + GHRP-2 signifi cantly increased com- pared with naive and vehicle groups (P = 0.0007, P = 0.0038 and P = 0.0166, respectively). The median survival time was longer in 5-FU + GHRP-2 treated mice than in those with 5-FU, although it was not signifi cant (18 d versus 15.5 d, P = 0.7). For the fi rst time, we demonstrated that the addition of GHRP-2 to cytotoxic therapy with 5-FU improved appetite in tumour-bearing mice with anorexia/cachexia syndrome in early stage. These data suggest that GHRP-2 may improve the effi cacy of therapy and the quality of life of cancer patients thank to the amelioration of their nutritional state.展开更多
The prevalence of overweight and obesity has increased worldwide.Obesity is a well-known risk factor of type 2 diabetes mellitus and cardiovascular disease and raises public health concerns.Many dietary guidelines enc...The prevalence of overweight and obesity has increased worldwide.Obesity is a well-known risk factor of type 2 diabetes mellitus and cardiovascular disease and raises public health concerns.Many dietary guidelines encourage the replacement of refined grains with whole grains(WGs)to enhance body weight management.Current evidence regarding interrelationships among WGs,body weight,and gut microbiota is limited and inconclusive.In this editorial,we comment on the article by Roager et al published in the recent issue of the Gut 2019;68(1):83-93.In the study,obese patients(25<body mass index<35 kg/m2)were randomly assigned to receive two 8-wk dietary controlling periods with WGs and refined grain-rich diet.The results showed significantly decreased body weight in the WG group.Either the composition of gut microbiota or short-chain fatty acids,the leading end product of fermentation of non-digestible carbohydrate by gut microbiota,did not differ between the two groups.The study highly indicated that a WG-rich diet reduced body weight independent of gut microbiota.We then raised some plausible mechanisms of how WGs might influence body weight and demonstrated more literature in line with WGs enhance body weight control through a microbiota-independent pathway.Possible mechanisms include:(1)The abundant dietary fiber contents of WGs increase satiety,satiation,energy excretion from stool,and energy expenditure simultaneously decreasing energy absorption and fat storage;(2)The plentiful amount of polyphenols of WGs improve energy expenditure by hampering adipocyte maturation and function;(3)The sufficient magnesium and zinc of WGs guarantee lean body mass growth and decrease fat mass;(4)The effect of WGs on brown adipose tissue is a key component of non-shivering thermogenesis;and(5)The increase of adiponectin by WGs enhances glucose utilization,lipid oxidation,and energy expenditure.展开更多
9th NPY Meeting was held for the f irst time in Japan in March 2008, which was organized by Akio Inui, Profes-sor and Chairman, Department of Psychosomatic In-ternal Medicine, Kagoshima University Graduate School of M...9th NPY Meeting was held for the f irst time in Japan in March 2008, which was organized by Akio Inui, Profes-sor and Chairman, Department of Psychosomatic In-ternal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan. We have invited him to write TOPIC HIGHLIGHT for WJG focused on ghrelin along the gut-brain axis.This TOPIC HIGHLIGHT is the 'ghrelin version' of the proceedings of 9th NPY Meeting and presents ex-amples of the critical interplay in ghrelin-NPY pathway in response to environmental,展开更多
文摘Three peptides, ghrelin, des-acyl ghrelin and obestatin are derived from a common prohormone, preproghrelin by posttranslational processing, originating from endocrine cells in the stomach. To examine the effects of these peptides, we applied the manometric measurement of gastrointestinal motility in freely moving conscious rat models. Ghrelin exerts stimulatory effects on the motility of antrum and duodenum in both fed and fasted state of animals. Des-acyl ghrelin exerts inhibitory effects on the motility of antrum, but not on the motility of duodenum in the fasted state of animals. Obestatin exerts inhibitory effects on the motility of antrum and duodenum in the fed state, but not in the fasted state of animals. NPY Y2 or Y4 receptors in the brain may mediate the action of ghrelin, CRF type 2 receptors in the brain mediate the action of des-acy ghrelin, whereas CRF type 1 and type 2 receptors in the brain mediate the action of obestatin. Vagal afferent pathways might be involved in the action of ghrelin, but not involved in the action of des-acyl ghrelin, whereas vagal afferent pathways might be partially involved in the action of obestatin.
基金Supported by (in part) A Grant-in-Aid for Scientic Research (B:16390208) from the Ministry of Education, Culture, Sports, Science and Technology of Japan (to A.I.)
文摘The cancer-associated anorexia-cachexia syndrome is observed in 80% of patients with advanced-stage cancer, and is one of the major obstacles in chemo- therapy. Ghrelin is a orexigenic hormone that has been proposed to prevent anorexia. Aim of the study was to determine whether the addition of the ghrelin agonist growth hormone releasing peptide 2 (GHRP-2) to cytotoxic therapy with 5-fluoruracil (5-FU) prevents the anorexia associated with chemotherapy in cancer cachectic mice. Thirty-three BALB/c female tumourbearing mice were randomized to receive a solution containing: (a) placebo; (b) GHRP-2; (c) 5-FU; or (d) 5-FU + GHRP-2. Ten BALB/c no tumour-bearing mice received placebo solution. Food intake and survival were checked. Six hours after the drug injection the cumulative food intake was signifi cantly increased in mice treated with the combination of 5-FU + GHRP-2 versus the 5-FU alone (P = 0.0096). On day 3, the cumulative food intake of mice treated with GHRP-2,5-FU and 5-FU + GHRP-2 signifi cantly increased com- pared with naive and vehicle groups (P = 0.0007, P = 0.0038 and P = 0.0166, respectively). The median survival time was longer in 5-FU + GHRP-2 treated mice than in those with 5-FU, although it was not signifi cant (18 d versus 15.5 d, P = 0.7). For the fi rst time, we demonstrated that the addition of GHRP-2 to cytotoxic therapy with 5-FU improved appetite in tumour-bearing mice with anorexia/cachexia syndrome in early stage. These data suggest that GHRP-2 may improve the effi cacy of therapy and the quality of life of cancer patients thank to the amelioration of their nutritional state.
文摘The prevalence of overweight and obesity has increased worldwide.Obesity is a well-known risk factor of type 2 diabetes mellitus and cardiovascular disease and raises public health concerns.Many dietary guidelines encourage the replacement of refined grains with whole grains(WGs)to enhance body weight management.Current evidence regarding interrelationships among WGs,body weight,and gut microbiota is limited and inconclusive.In this editorial,we comment on the article by Roager et al published in the recent issue of the Gut 2019;68(1):83-93.In the study,obese patients(25<body mass index<35 kg/m2)were randomly assigned to receive two 8-wk dietary controlling periods with WGs and refined grain-rich diet.The results showed significantly decreased body weight in the WG group.Either the composition of gut microbiota or short-chain fatty acids,the leading end product of fermentation of non-digestible carbohydrate by gut microbiota,did not differ between the two groups.The study highly indicated that a WG-rich diet reduced body weight independent of gut microbiota.We then raised some plausible mechanisms of how WGs might influence body weight and demonstrated more literature in line with WGs enhance body weight control through a microbiota-independent pathway.Possible mechanisms include:(1)The abundant dietary fiber contents of WGs increase satiety,satiation,energy excretion from stool,and energy expenditure simultaneously decreasing energy absorption and fat storage;(2)The plentiful amount of polyphenols of WGs improve energy expenditure by hampering adipocyte maturation and function;(3)The sufficient magnesium and zinc of WGs guarantee lean body mass growth and decrease fat mass;(4)The effect of WGs on brown adipose tissue is a key component of non-shivering thermogenesis;and(5)The increase of adiponectin by WGs enhances glucose utilization,lipid oxidation,and energy expenditure.
文摘9th NPY Meeting was held for the f irst time in Japan in March 2008, which was organized by Akio Inui, Profes-sor and Chairman, Department of Psychosomatic In-ternal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan. We have invited him to write TOPIC HIGHLIGHT for WJG focused on ghrelin along the gut-brain axis.This TOPIC HIGHLIGHT is the 'ghrelin version' of the proceedings of 9th NPY Meeting and presents ex-amples of the critical interplay in ghrelin-NPY pathway in response to environmental,
