Dietary fiber can be fermented and utilized by gut microbiota to reshape the gut microbiota, thereby alleviating constipation. This experiment mainly studied the physicochemical functions of hawthorn soluble dietary fiber (HSDF)and its effect and mechanism in alleviating constipation in mice. Forty-five mice were divided into blank control group C, model group M, positive control HS group, low-dose LHSDF group (1 g/kg/bw), and high-dose HHSDF group (2 g/kg/bw). The mice were modeled at a dose of 10 mg/kg/bw of loperamide hydrochloride for 7 days, while the remaining groups were orally administered an equal amount of distilled water and test samples. After continuous gavage for 45 days we performed a bowel movement test, and then continued gavage for 7 days and performed a small intestine propulsion test and indicator testing. The results showed that HSDF is mainly composed of galacturonic acid, belonging to the type I crystal structure, with a loose surface resembling a snowflake, a small molecular weight, and strong water-holding and antioxidant abilities. Animal experiments showed that compared with group M, HSDF significantly upregulated AQP3 and AQP8 by 52.67% and 164.54%, respectively, and downregulated AQP9 protein expression by 45.88%, thereby promoting intestinal peristalsis. It can also alleviate constipation by increasing the levels of excitatory hormones such as MTL, GAS, and SP in the gastrointestinal tract, and reducing the levels of inhibitory hormones such as SS, NO, and MDA. In addition, HSDF can reduce the levels of inflammatory factors such as IL-6 and PL-1 β, increase the content of various short-chain fatty acids, alleviate intestinal inflammation, maintain intestinal integrity, and promote defecation. It can also promote the growth of probiotics such as Bacteroides, inhibit the growth of harmful bacteria such as Bifidobacterium and Lactobacillus, and alter the diversity of gut microbiota.

The rapidly rising incidence of obesity, coupled with type 2 diabetes mellitus (T2DM), is a growing concern. Glucagon-like peptide 1 (GLP-1), an endogenous peptide secreted by enteroendocrine L-cells, demonstrates exceptional pharmacological potential for the treatment of T2DM and obesity, primarily through its pivotal roles in regulating glucose homeostasis, stimulating glucose-dependent insulin secretion, and promoting satiety. Considering its proven efficacy in glucoregulation and weight loss, GLP-1 receptor agonists (GLP-1RAs) have emerged as a revolutionary breakthrough in the arena of diabetes management and weight control. Additional gastrointestinal hormones, such as glucose-dependent insulinotropic peptide (GIP) and glucagon, exhibit structural similarities to GLP-1 and work synergistically to lower blood glucose levels or aid in weight loss. Today, various classes of gut hormone receptor multiple agonists are steadily progressing through development and clinical trials, including dual GLP-1/glucagon receptor agonists (first discovered in 2009), dual GLP-1/GIP receptor agonists (first described in 2013), and triple GLP-1/GIP/glucagon receptor agonists (initially designed in 2015). The GLP-1/GIP receptor co-agonist, tirzepatide, was approved by the U.S. Food and Drug Administration (FDA) for the treatment of T2DM, outperforming basal insulin or selective GLP-1RAs by providing superior HbA1c reductions. Remarkably, tirzepatide also facilitated unprecedented weight loss of up to 22.5% in non-diabetic individuals living with obesity. This result is comparable to those achieved with certain types of bariatric surgery. Therefore, the advent of gut hormone multi-agonists signifies the dawn of an exciting new era in peptide-based therapy for obesity and T2DM. This review offers a comprehensive summary of the various types of gut hormone multiple agonists, including their discovery, development, action of mechanisms, and clinical effectiveness. We further delve into potential hurdles, limitations, and prospective advancements in the field.

T-2 toxin is one of trichothecene mycotoxins, which can impair appetite and decrease food intake. However, the specific mechanisms for T-2 toxin-induced anorexia are not fully clarified. Multiple research results had shown that gut microbiota have a significant effect on appetite regulation. Hence, this study purposed to explore the potential interactions of the gut microbiota and appetite regulate factors in anorexia induced by T-2 toxin. The study divided the mice into control group (CG, 0 mg/kg BW T-2 toxin) and T-2 toxin-treated group (TG, 1 mg/kg BW T-2 toxin), which oral gavage for 4 weeks, to construct a subacute T-2 toxin poisoning mouse model. This data proved that T-2 toxin was able to induce an anorexia in mice by increased the contents of gastrointestinal hormones (CCK, GIP, GLP-1 and PYY), neurotransmitters (5-HT and SP), as well as pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) in serum of mice. T-2 toxin disturbed the composition of gut microbiota, especially, Faecalibaculum and Allobaculum, which was positively correlated with CCK, GLP-1, 5-HT, IL-1β, IL-6 and TNF-α, which played a certain role in regulating host appetite. In conclusion, gut microbiota changes (especially an increase in the abundance of Faecalibaculum and Allobaculum) promote the upregulation of gastrointestinal hormones, neurotransmitters, and pro-inflammatory cytokines, which may be a potential mechanism of T-2 toxin-induced anorexia.

OBJECTIVE: To observe the effect of acupuncture on gastroesophageal reflux disease (GERD) based on the \"heart-stomach connection\" theory, and to explore its possible mechanisms.
METHODS: Seventy patients with GERD were randomly divided into an acupuncture group (35 cases, 2 cases dropped out) and a medication group (35 cases, 1 case dropped out). The patients in the acupuncture group received acupuncture at bilateral Shenmen (HT 7), Neiguan (PC 6), Burong (ST 19), Tianshu (ST 25), Zusanli (ST 36), Gongsun (SP 4), and Zhongwan (CV 12), with needles retained for 30 min, every other day, three times a week. The patients in the medication group were treated with oral omeprazole capsules, once daily, 20 mg each time. Both groups were treated for 8 weeks. Before and after treatment, the GERD questionnaire (GERDQ), GERD-quality of life scale (GERD-QOL), Hamilton depression scale-24 (HAMD-24), Zung self-rating depression scale (SDS), and Zung self-rating anxiety scale (SAS) scores were observed. Serum levels of gastrointestinal hormones (gastrin [GAS], motilin [MTL], and vasoactive intestinal peptide [VIP]) were measured, and the clinical efficacy of both groups was evaluated. Correlation between pre-treatment GERDQ score and GERD-QOL score, HAMD-24 score, SDS score, and SAS score was analyzed.
RESULTS: After treatment, the scores of GERDQ, HAMD-24, SDS, and SAS were decreased (P<0.001) and the scores of GERD-QOL were increased (P<0.001), serum levels of GAS and MTL were increased (P<0.001) in both groups, while the serum level of VIP in the acupuncture group was decreased (P<0.001) compared with those before treatment. The acupuncture group had higher GERD-QOL score and lower SAS score than the medication group (P<0.05), with lower serum VIP level (P<0.05). The total effective rate was 75.8% (25/33) in the acupuncture group, and 76.5% (26/34) in the medication group, with no significant difference between the two groups (P>0.05). GERDQ score was negatively correlated with GERD-QOL scores (r =-0.762, P<0.01) and positively correlated with HAMD-24 score, SDS score, and SAS score (r =0.709, 0.649, 0.689, P<0.01) before treatment.
CONCLUSIONS: Based on the \"heart-stomach connection\" theory, acupuncture could effectively improve clinical symptoms, quality of life, and negative emotions in patients with GERD. Its mechanism may be related to the regulation of gastrointestinal hormone levels, thereby promoting the contraction of the lower esophageal sphincter.
目的：观察基于“心胃相关”理论针刺对胃食管反流病的影响，探讨其可能作用机制。方法：将70例胃食管反流病患者随机分为针刺组（35例，脱落2例）和西药组（35例，脱落1例）。针刺组予针刺治疗，穴取双侧神门、内关、不容、天枢、足三里、公孙及中脘，留针30 min，隔日1次，每周3次；西药组予口服奥美拉唑胶囊，每日1次，每次20 mg。两组均治疗8周。观察两组患者治疗前后胃食管反流病问卷（GERDQ）、胃食管反流病生存质量量表（GERD-QOL）、汉密尔顿抑郁量表（HAMD-24）、Zung抑郁自评量表（SDS）、Zung焦虑自评量表（SAS）评分，检测治疗前后血清胃肠激素[胃泌素（GAS）、胃动素（MTL）、血管活性肠肽（VIP）]含量，并评定两组临床疗效。对治疗前GERDQ评分与GERD-QOL、HAMD-24、SDS、SAS评分进行相关性分析。结果：治疗后，两组GERDQ、HAMD-24、SDS、SAS评分均较治疗前降低（P<0.001），GERD-QOL评分均较治疗前升高（P<0.001），血清GAS、MTL含量均较治疗前升高（P<0.001），针刺组血清VIP含量较治疗前降低（P<0.001）；针刺组GERD-QOL评分高于西药组（P<0.05），SAS评分低于西药组（P<0.05），血清VIP含量低于西药组（P<0.05）。针刺组总有效率为75.8%（25/33），西药组总有效率为76.5%（26/34），组间比较差异无统计学意义（P>0.05）。治疗前，GERDQ评分与GERD-QOL评分存在负相关关系（r =-0.762，P<0.01），与HAMD-24、SDS、SAS评分存在正相关关系（r =0.709、0.649、0.689，P<0.01）。结论：基于“心胃相关”理论针刺能有效改善胃食管反流病患者的临床症状、生活质量、不良情绪，其机制可能与调节胃肠激素水平，进而促进食管下括约肌收缩有关。.

Bone resorption follows a circadian rhythm, with a marked reduction in circulating markers of resorption (such as carboxy-terminal telopeptide region of collagen type I in serum) in the postprandial period. Several gut hormones, including glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP1) and GLP2, have been linked to this effect in humans and rodent models. These hormones are secreted from enteroendocrine cells in the gastrointestinal tract in response to a variety of stimuli and effect a wide range of physiological processes within and outside the gut. Single GLP1, dual GLP1-GIP or GLP1-glucagon and triple GLP1-GIP-glucagon receptor agonists have been developed for the treatment of type 2 diabetes mellitus and obesity. In addition, single GIP, GLP1 and GLP2 analogues have been investigated in preclinical studies as novel therapeutics to improve bone strength in bone fragility disorders. Dual GIP-GLP2 analogues have been developed that show therapeutic promise for bone fragility in preclinical studies and seem to exert considerable activity at the bone material level. This Review summarizes the evidence of the action of gut hormones on bone homeostasis and physiology.

Gut peptides play a role in signaling appetite control in the hypothalamus. Limited knowledge exists regarding the release of these peptides in individuals with obesity before and during external stimuli. We hypothesize that the expression of gut peptides is different in the fasting and postprandial states in the scenario of obesity. PubMed/MEDLINE, Scopus, and Science Direct electronic databases were searched. The meta-analysis was performed using Review Manager Software. Randomized controlled trials that measured gut peptides in both obese and lean subjects were included in the analysis. A total of 552 subjects with obesity were enrolled in 25 trials. The gut peptide profile did not show any significant difference between obese and lean subjects for glucagon-like peptide 1 (95% confidence interval [CI], -1.21 to 0.38; P = .30), peptide YY (95% CI, -1.47 to 0.18; P = .13), and cholecystokinin (95% CI, -1.25 to 1.28; P = .98). Gut peptides are decreased by an increased high-fat, high-carbohydrate diet and by decreased chewing. There is no statistically significant difference in gut peptides between individuals with obesity and leanness in a fasting state. However, the release of gut peptides is affected in individuals with obesity following external stimuli, such as dietary interventions and chewing. Further studies are necessary to investigate the relationship between various stimuli and the release of gut peptides, as well as their impact on appetite regulation in subjects with obesity.

OBJECTIVE: The hypothesis of this study is to determine the effects of intracerebroventricular (icv) prokineticin 2 infusion on food consumption and body weight and to elucidate whether it has effects on energy expenditure via the hypothalamus-pituitary-thyroid (HPT) axis in adipose tissue.
METHODS: A total of 40 rats were used in the study and 4 groups were established: Control, Sham, Prokineticin 1.5 and Prokineticin 4.5 (n=10). Except for the Control group, rats were treated intracerebroventricularly via osmotic minipumps, the Sham group was infused with aCSF (vehicle), and the Prokineticin 1.5 and Prokineticin 4.5 groups were infused with 1.5 nMol and 4.5 nMol prokineticin 2, respectively. Food and water consumption and body weight were monitored during 7-day infusion in all groups. At the end of the infusion, the rats were decapitated and serum TSH, fT4 and fT3 levels were determined by ELISA. In addition, PGC-1α and UCP1 gene expression levels in white adipose tissue (WAT) and brown adipose tissue (BAT), TRH from rat hypothalamic tissue were determined by real-time PCR.
RESULTS: Icv prokineticin 2 (4.5 nMol) infusion had no effect on water consumption but reduced daily food consumption and body weight (p<0.05). Icv prokineticin 2 (4.5 nMol) infusion significantly increased serum TSH, fT4 and fT3 levels when compared to Control and Sham groups (p<0.05). Also, icv prokineticin 2 (4.5 nMol) infusion increased the expression of TRH in the hypothalamus tissue and expression of PGC-1α UCP1 in the WAT and BAT (p<0.05).
CONCLUSIONS: Icv prokineticin 2 (4.5 nMol) infusion may suppress food consumption via its receptors in the hypothalamus and reduce body weight by stimulating energy expenditure and thermogenesis in adipose tissue through the HPT axis.

Prokineticin 1 (PROK1) is an important factor in pregnancy establishment in pigs, acting at the embryo-maternal interface and the corpus luteum (CL). Estradiol-17β (E2) is the primary pregnancy recognition signal in pigs, and its effects are augmented by luteotropic prostaglandin E2 (PGE2). On the contrary, prostaglandin F2α (PGF2α) exerts mainly a luteolytic effect. The present study aimed to elucidate whether E2, PGE2, and PGF2α regulate the expression of PROK1 and its receptors in the porcine CL and to determine the PROK1 effect on luteal endothelial cells and pathways that may be involved in this regulation. The effects of E2, PGE2, and PGF2α on the expressions of PROK1 and its receptors in the CL were studied using an in vitro model of ultrathin luteal tissue explants model. Additionally, the effects of E2 and PGE2 on the PROK1 system were determined using an in vivo approach, in which the hormones were administered into the uterine lumen to imitate their secretion by embryos. Endothelial cell proliferation was measured using the colorimetric method. E2 acting via estrogen receptors simulated the mRNA and protein expressions of PROK1 and PROKR1 in CL explants in vitro (p < 0.05). The simultaneous action of E2 with PGE2 enhanced the expression of luteal PROK1 mRNA in vitro (p < 0.05). Estradiol-17β acting alone significantly increased PROK1 mRNA levels in vivo, whereas E2 simultaneously administered with PGE2 significantly elevated the PROK1 mRNA expression and PROKR1 mRNA and protein contents in CLs adjacent to uterine horns receiving hormonal infusion compared with CLs adjacent to placebo-treated uterine horns (p < 0.01). The PROK1 protein expression was significantly higher in the CLs of pigs treated with E2, PGE2, and E2 together with PGE2 than in the control group. PGF2α increased the PROK1 mRNA content in CLs on days 12 and 14 of the estrous cycle (p < 0.05). The expression of PROKR2 at the mRNA and protein levels remained unchanged in response to in vitro and in vivo treatments. PROK1 stimulated the proliferation of luteal endothelial cells by activating the MAPK, AKT, and mTOR pathways (p < 0.05). In summary, the luteal expressions of PROK1 and PROKR1 in early pregnancy are regulated by E2 and PGE2. PROK1 stimulates luteal angiogenesis by activating the MAPK, AKT, and mTOR pathways. The regulation of luteal PROK1 expression by PGF2α indicates PROK1\'s putative role during luteolysis. We conclude that PROK1-PROKR1 signaling supports luteal function during CL rescue in pregnancy in pigs.

Glycomacropeptide (GMP) has a unique amino acid profile which may make less satiating than other dietary proteins. This study assessed the feasibility and likely acceptability of a leucine-enriched GMP drink and determined appetite response in older adults (OA). Thirteen OA (11f; 70 ± 4 years) were recruited for sensory assessments of a leucine-enriched GMP drink when mixed with water and with fruit smoothie, compared with whey protein isolate (WHEY). Participants also partook in a single focus group exploring acceptability to protein and supplementation. Separately, a counterbalanced, double-blind study with twelve OA (8f; 69 ± 3 years) was conducted to determine appetite and gut hormone responses. Fasting subjective appetite was recorded using visual analogue scales and a fasted venous blood sample was collected (to measures acyl-ghrelin, PYY, GLP-1, and CCK) before participants consumed either: GMP protein (27g + 3g leucine, 350 mL water), WHEY (30g, 350 mL water), or water. Participants rested for 240 min, with appetite measures and blood sampling throughout. An ad libitum pasta-based meal was then consumed. Sensory testing revealed low pleasantness rating for GMP in water vs. WHEY (16 ± 14 vs 31 ± 24, p = 0.016). GMP addition to smoothie reduced pleasantness (26 ± 21 vs. 61 ± 29, p = 0.009) and worsened the aroma (46 ± 15 vs. 69 ± 28, p = 0.014). The focus group revealed uncertainty of protein needs and a scepticism of supplements, with preference for food. Gut hormone response did not differ between GMP and WHEY (nAUC for all gut hormones p > 0.05). There was no difference between conditions for lunch ad libitum intake (549 ± 171 kcal, 512 ± 238 kcal, 460 ± 199 kcal for GMP, WHEY, and water, p = 0.175), or for subjective appetite response. Leucine-enriched GMP was not less satiating than WHEY, and low palatability and scepticism of supplements question the likely acceptability of GMP supplementation. Providing trusted nutritional advice and food enrichment/fortification may be preferred strategies for increasing protein intake in OA.

BACKGROUND: Prokineticin 2 (PROK2), an important neuropeptide that plays a key role in the neuronal migration of gonadotropin-releasing hormone (GnRH) in the hypothalamus, is known to have regulatory effects on the gonads. In the present study, the impact of intracerebroventricular (icv) PROK2 infusion on hypothalamic-pituitary-gonadal axis (HPG) hormones, testicular tissues, and sperm concentration was investigated.
RESULTS: Rats were randomly divided into four groups: control, sham, PROK2 1.5 and PROK2 4.5. Rats in the PROK2 1.5 and PROK2 4.5 groups were administered 1.5 nmol and 4.5 nmol PROK2 intracerebroventricularly for 7 days via an osmotic mini pump (1 µl/h), respectively. Rat blood serum follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone hormone levels were determined with the ELISA method in the blood samples after 7 days of infusion. GnRH mRNA expression was determined with the RT-PCR in hypothalamus tissues. analyze Sperm concentration was determined, and testicular tissue was examined histologically with the hematoxylin-eosin staining method. It was observed that GnRH mRNA expression increased in both PROK2 infusion groups. Serum FSH, LH and testosterone hormone levels also increased in these groups. Although sperm concentration increased in PROK2 infusion groups when compared to the control and sham, the differences were not statistically significant. Testicular tissue seminiferous epithelial thickness was higher in the PROK2 groups when compared to the control and sham groups.
CONCLUSIONS: The present study findings demonstrated that icv PROK2 infusion induced the HPG axis. It could be suggested that PROK2 could be a potential agent in the treatment of male infertility induced by endocrinological defects.