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One of the most striking examples of dysfunctional hypothalamic signaling of energy homeostasis is observed in patients with hypothalamic lesions leading to hypothalamic obesity (HO). This drastic condition is frequently seen in patients with craniopharyngioma (CP), an embryological tumor located in the hypothalamic and/or pituitary region, frequently causing not only hypopituitarism, but also leading to damage of medial hypothalamic nuclei due to the tumor and its treatment. HO syndrome in CP patients is characterized by fatigue, decreased physical activity, uncontrolled appetite, and morbid obesity, and is associated with insulin and leptin resistance. Mechanisms leading to the profoundly disturbed energy homeostasis are complex. This review summarizes different aspects of important clinical studies as well as data obtained in rodent studies. In addition a model is provided describing how medial hypothalamic lesion can interact simultaneously with several weight regulating circuitries.

The negative effects of malnourishment in utero have been widely explored; the effects of increased maternal macronutrient intake are not known in relation to high fibre, and have been inconclusive with regard to high protein. In the present study, virgin Wistar dams were fed either a control (C), high-protein (40 %, w/w; HP) or high-prebiotic fibre (21·6 %, w/w; HF) diet throughout pregnancy and lactation. Pups consumed the C diet from 3 to 14·5 weeks of age, and then switched to a high-fat/sucrose diet for 8 weeks. A dual-energy X-ray absorptiometry scan and an oral glucose tolerance test were performed and plasma satiety hormones measured. The final body weight and the percentage of body fat were significantly affected by the interaction between maternal diet and offspring sex: weight and fat mass were higher in the female offspring of the HP v. HF dams. No differences in body weight or fat mass were seen in the male offspring. There was a significant sex effect for fasting and total AUC for ghrelin and fasting GIP, with females having higher levels than males. Liver TAG content and plasma NEFA were lower in the offspring of high-prebiotic fibre dams (HF1) than in those of high-protein dams (HP1) and control dams (C1). Intestinal expression of GLUT2 was decreased in HF1 and HP1 v. C1. The maternal HP and HF diets had lasting effects on body fat and hepatic TAG accumulation in the offspring, particularly in females. Whereas the HP diet predisposes to an obese phenotype, the maternal HF diet appears to reduce the susceptibility to obesity following a high-energy diet challenge in adulthood. [ABSTRACT FROM AUTHOR]

Roux-en-Y gastric bypass ( RYGB) surgery reverses type 2 diabetes mellitus ( T2DM) in approximately 80% of patients. Ghrelin regulates glucose homeostasis, but its role in T2DM remission after RYGB surgery is unclear. Nine obese T2DM subjects underwent a mixed meal tolerance test before and at 1 and 12 months after RYGB surgery. Changes in ghrelin, body weight, glucagon-like polypeptide-1 ( GLP-1, glucose tolerance and insulin sensitivity (IS) were measured. At 1 month, body weight, glycaemia and IS were improved, while ghrelin concentrations were reduced (p < 0.05). After 12 months, body weight and fasting glucose were reduced (30 and 16%, respectively; p < 0.05) and IS was enhanced (threefold; p < 0.05). Ghrelin suppression improved by 32% at 12 months (p < 0.05), and this was associated with weight loss (r = 0.72, p = 0.03), enhanced IS (r = −0.78, p = 0.01) and peak postprandial GLP-1 (r = −0.73, p = 0.03). These data suggest that postprandial ghrelin suppression may be part of the mechanism that contributes to diabetes remission after RYGB surgery. [ABSTRACT FROM AUTHOR]

Obesity is an increasing health problem. Because drug treatments are limited, diets remain popular. High-protein diets (HPD) reduce body weight (BW), although the mechanisms are unclear. We investigated physiological mechanisms altered by switching diet induced obesity (DIO) rats from Western-type diet (WTD) to HPD. Male rats were fed standard (SD) or WTD (45% calories from fat). After developing DIO (50% of rats), they were switched to SD (15% calories from protein) or HPD (52% calories from protein) for up to 4 weeks. Food intake (FI), BW, body composition, glucose tolerance, insulin sensitivity, and intestinal hormone plasma levels were monitored. Rats fed WTD showed an increased FI and had a 25% greater BW gain after 9 wk compared with SD (P < 0.05). Diet-induced obese rats switched from WTD to HPD reduced daily FI by 30% on day 1, which lasted to day 9 (–9%) and decreased BW during the 2-wk period compared with SD/SD (P < 0.05). During these 2 wk, WTD/HPD rats lost 72% more fat mass than WTD/SD (P < 0.05), whereas lean mass was unaltered. WTD/HPD rats had lower blood glucose than WTD/SD at 30 min postglucose gavage (P < 0.05). The increase of pancreatic polypeptide and peptide YY during the 2-h dark-phase feeding was higher in WTD/HPD compared with WTD/SD (P < 0.05). These data indicate that HPD reduces BW in WTD rats, which may be related to decreased FI and the selective reduction of fat mass accompanied by improved glucose tolerance, suggesting relevant benefits of HPD in the treatment of obesity. [ABSTRACT FROM AUTHOR]

The article aims at analyzing the effect of obesity on gut microbiota. It states that use of gut microbiota has increased in clinics and researches because of the modified human ancestral genomes. It further mentions that the gut consists of 15,000 bacterial species which can effect health and chronic diseases.

Ghrelin levels are suppressed in obese subjects and subjects with Type 2 diabetes mellitus (T2DM). Exercise-stimulated decreases in plasma ghrelin are a proposed mediator of exercise-induced satiety in healthy subjects. However, exercise-induced satiety and the impact of impaired ghrelin levels in obesity-related disease are poorly understood. Therefore our objective was to investigate exercise-induced postprandial satiety and ghrelin responses in overweight subjects with T2DM (N = 8) and healthy controls (N = 7). Visual analog scale satiety questionnaires (assessing hunger, thirst, food that could be eaten, nausea, and fullness) and circulating levels of glucose, insulin, and total and acylated ghrelin were measured at baseline and in response to a 75 g oral glucose load, provided immediately after an aerobic exercise bout (1 h at 50% Wmax) or no exercise (rest trial), on two separate occasions. Baseline levels of total (284.4 ± 15.9 and 397.6 ± 35.2 pmol/l) and acylated ghrelin (7.9 ± 1.0 and 13.7 ± 1.2 pmol/l) were lower in subjects with T2DM compared with healthy subjects (P < 0.05). In the rest trial, post- vs. preprandial feeling of fullness increased in healthy subjects but decreased in subjects with T2DM (healthy vs. T2DM; P < 0.05). Exercise increased postprandial fullness in the T2DM group (P < 0.05), while plasma ghrelin levels were unaffected. Our data suggest that the presence of T2DM likely drives suppressed ghrelin levels and poor appetite regulation, but a single exercise bout is sufficient to restore oral glucose-induced fullness independently of ghrelin. [ABSTRACT FROM AUTHOR]

Background: Bariatric procedures excluding the proximal small intestine improve glycemic control in type 2 diabetes within days. To gain insight into the mediators involved, we investigated factors regulating glucose homeostasis in patients with type 2 diabetes treated with the novel endoscopic duodenal-jejunal bypass liner (DJBL). Methods: Seventeen obese patients (BMI 30-50 kg/m) with type 2 diabetes received the DJBL for 24 weeks. Body weight and type 2 diabetes parameters, including HbA and plasma levels of glucose, insulin, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon, were analyzed after a standard meal before, during, and 1 week after DJBL treatment. Results: At 24 weeks after implantation, patients had lost 12.7 ± 1.3 kg ( p < 0.01), while HbA had improved from 8.4 ± 0.2 to 7.0 ± 0.2 % ( p < 0.01). Both fasting glucose levels and the postprandial glucose response were decreased at 1 week after implantation and remained decreased at 24 weeks (baseline vs. week 1 vs. week 24: 11.6 ± 0.5 vs. 9.0 ± 0.5 vs. 8.6 ± 0.5 mmol/L and 1,999 ± 85 vs. 1,536 ± 51 vs. 1,538 ± 72 mmol/L/min, both p < 0.01). In parallel, the glucagon response decreased (23,762 ± 4,732 vs. 15,989 ± 3,193 vs. 13,1207 ± 1,946 pg/mL/min, p < 0.05) and the GLP-1 response increased (4,440 ± 249 vs. 6,407 ± 480 vs. 6,008 ± 429 pmol/L/min, p < 0.01). The GIP response was decreased at week 24 (baseline-115,272 ± 10,971 vs. week 24-88,499 ± 10,971 pg/mL/min, p < 0.05). Insulin levels did not change significantly. Glycemic control was still improved 1 week after explantation. Conclusions: The data indicate DJBL to be a promising treatment for obesity and type 2 diabetes, causing rapid improvement of glycemic control paralleled by changes in gut hormones. [ABSTRACT FROM AUTHOR]

Bariatric surgeries are hypothesized to produce weight loss and improve diabetes control by multiple mechanisms including gastric restriction and lower gut stimulation; the relative importance of these mechanisms remains poorly understood. We compared the effects of a typical foregut procedure, sleeve gastrectomy, (SG) with a primarily hindgut surgery, ileal transposition (IT), alone and together (SGIT), or sham manipulations, on food intake, body weight, gut hormones, glucose tolerance, and key markers of glucose homeostasis in peripheral tissues of adult male Sprague-Dawley rats (450-550 g, n 7-9/group). SG, IT, and SGIT surgeries produced transient reduction in food intake and weight gain; the effects of SG and IT on intake and body weight were nonadditive. SG, IT, and SGIT surgeries resulted in increased tissue expression and plasma concentrations of the lower gut hormones glucagon-like peptide- 1 and peptide YY and decreased plasma glucose-dependent insulinotropic peptide, insulin, and leptin concentrations. Despite transient effects on intake and weight gain, the SG, IT, and SGIT surgeries produced a significant improvement in glucose tolerance. In support of glycemic improvements, the protein abundance of key markers of glucose metabolism (e.g., GLUT4, PKA, IRS-1) in muscle and adipose tissue were increased, whereas the expression of key gluconeogenic enzyme in liver (G-6-Pase) were decreased following the surgeries. Therefore, our data suggest that enhanced lower gut stimulation following SG, IT, and SGIT surgeries leads to transient reduction in food intake and weight gain together with enhanced secretion of lower gut hormones and improved glucose clearance by peripheral tissues. [ABSTRACT FROM AUTHOR]

Background and Aims: Roux-en-Y gastric bypass (RYGB) is effective in controlling blood glucose in obese patients with type 2 diabetes (T2DM). The alterations of gut hormones involving in glucose metabolism may play an important role. Our aim was to explore the short-term effects of Billroth II gastrojejunostomy (a similar type of RYGB) on glucose metabolism and gut hormone modulations in nonobese patients with different levels of blood glucose tolerance. Methods: Twenty one nonobese gastric cancer patients with different levels of blood glucose tolerance were submitted to Billroth II gastrojejunostomy. Among them, seven had T2DM, seven with impaired glucose tolerance (IGT) and the other seven had normal glucose tolerance (NGT). Body weight, glucose parameters, responses of plasma glucagon-like peptide-1 (GLP-1), peptide YY (PYY) and gastric inhibitory polypeptide (GIP) to 75 g glucose were measured at baseline and 3 months after surgery. Results: Similar weight losses were observed in all groups. Blood glucose was reduced in T2DM and IGT patients. Fasting and 30-min plasma glucose were increased significantly in NGT. GLP-1 showed insignificant alterations in all groups. PYY was evaluated in T2DM and IGT but remained unchanged in the NGT group. Decreased fasting and AUC GIP were observed in patients with T2DM; however, fasting and 30-min GIP were increased in NGT patients. Conclusions: Billroth II gastrojejunostomy is effective in reducing blood glucose in nonobese patients with T2DM and IGT but could deteriorate early blood glucose in nonobese NGT in a 3-month time period. Variations of glucose and gut hormone changes in the three groups suggest a role of proximal intestine in the pathophysiology of T2DM. [Copyright &y& Elsevier]

Abstract: Prevention of weight gain in adults is a major public health target. Animal experiments have consistently demonstrated a relationship between fermentable carbohydrate intake, such as oligofructose, anorectic gut hormones, and appetite suppression and body weight control. This study was designed to determine the dose of oligofructose which would augment the release of anorectic gut hormones and reduce appetite consistently in non-obese humans. Twelve non-obese participants were recruited for a 5-week dose-escalation study. Following a 9–14-day run-in, participants increased their daily oligofructose intake every week from 15, 25, 35, 45, to 55g daily. Subjective appetite and side effects were monitored daily. Three-day food diaries were completed every week. Appetite study sessions explored the acute effects of 0, 15, 35, and 55g oligofructose on appetite-related hormones, glycaemia, subjective appetite, and energy intake. In the home environment, oligofructose suppressed hunger, but did not affect energy intake. Oligofructose dose-dependently increased peptide YY, decreased pancreatic polypeptide and tended to decrease ghrelin, but did not significantly affect appetite profile, energy intake, glucose, insulin, or glucagon-like peptide 1 concentrations during appetite study sessions. In conclusion, oligofructose supplementation at ⩾35g/day increased peptide YY and suppressed pancreatic polypeptide and hunger; however, energy intake did not change significantly. [Copyright &y& Elsevier]

Updated prevalence estimates of all 3 components of the Female Athlete Triad, a syndrome characterized by low energy availability, functional hypothalamic amenorrhea, and osteoporosis, is low (0 %-16 %), however, estimates of 1 or 2 concurrent components approach 50 %-60 % among certain athlete groups. Recent research identifies components of the Triad among female adolescent athletes, particularly those participating in leanness sports, such as endurance running. This is alarming, as adolescents require adequate nutrition and normal hormone function to optimize bone mineral gains during this critical developmental period. Current literature highlights new assessments, such as measurements of bone microarchitecture and hormone levels to better evaluate bone strength and the hormonal and metabolic profile of athletes with and at risk for the Triad. Recent data also provides support for additional potential consequences of the Triad, such as endothelial dysfunction and related cardiovascular effects, stress fractures, and musculoskeletal injuries. Additional prospective research is needed to evaluate long-term indicators and consequences of the Triad and identify effective behavioral treatment strategies. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: We carried out a systematic review of clinical studies investigating glucagon-like peptide-1 (GLP-1) secretion in patients with type 2 diabetes and non-diabetic controls and performed meta-analyses of plasma total GLP-1 concentrations during an OGTT and/or meal test. Methods: Random effects models for the primary meta-analysis and random effects meta-regression, subgroup and regression analyses were applied. Results: Random effects meta-analysis of GLP-1 responses in 22 trials during 29 different stimulation tests showed that patients with type 2 diabetes ( n = 275) and controls without type 2 diabetes ( n = 279) exhibited similar responses of total GLP-1 ( p = NS) as evaluated from peak plasma concentrations (weighted mean difference [95% CI] 1.09 pmol/l [−2.50, 4.67]), total AUC (tAUC) (159 pmol/l×min [−270, 589]), time-corrected tAUC (tAUC min) (0.99 pmol/l [−1.28, 3.27]), incremental AUC (iAUC) (−122 pmol/l×min [−410, 165]) and time-corrected iAUC (iAUC min) (−0.49 pmol/l [−2.16, 1.17]). Fixed effects meta-analysis revealed higher peak plasma GLP-1 concentrations in patients with type 2 diabetes. Subgroup analysis showed increased responses after a liquid mixed meal test (peak, tAUC and tAUC min) and after a 50 g OGTT (AUC and tAUC min), and reduced responses after a solid mixed meal test (tAUC min) among patients with type 2 diabetes. Meta-regression analyses showed that HbA and fasting plasma glucose predicted the outcomes iAUC and iAUC min, respectively. Conclusions/interpretation: The present analysis suggests that patients with type 2 diabetes, in general, do not exhibit reduced GLP-1 secretion in response to an OGTT or meal test, and that deteriorating glycaemic control may be associated with reduced GLP-1 secretion. [ABSTRACT FROM AUTHOR]

There has been considerable debate about the metabolic effects of restricting carbohydrate intake in weight and diabetes management. However, the American Diabetes Association has noted that weight and metabolic improvements can be achieved with low carbohydrate, low fat (implicitly higher carbohydrate), or a Mediterranean style diet (usually an intermediate level of carbohydrate). Our paper addresses variability in the definition for low or restricted carbohydrate, the effects of carbohydrate restriction on diabetes-related health outcomes, strategies for restricting carbohydrate intake, and potential genetic variability in response to dietary carbohydrate restriction. Issues for future research are also addressed. [ABSTRACT FROM AUTHOR]

Abstract: Background: Changes in glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) levels after bariatric surgery have been proposed as a mechanism for long-term maintenance of weight loss and improvement in glucose homeostasis postoperatively. The objective of the present study was to assess the changes in GLP-1, PYY, insulin, and glucose levels after laparoscopic sleeve gastrectomy (SG). Methods: Ten morbidly obese patients without type 2 diabetes (3 male, 7 female; body mass index [BMI] 47.92±2.06 kg/m2) were evaluated preoperatively and at 6 weeks, 6 months, and 12 months after SG. Total GLP-1, total PYY, insulin, and glucose were measured in fasting state and every 30 minutes after ingestion of 75 g glucose for a total time of 120 minutes. Results: BMI decreased markedly postoperatively (P<.001). Postprandial total GLP-1 and total PYY responses, measured by the area under the curve (AUC), were significantly increased by the sixth postoperative week compared with preoperative period (P<.001). Fasting insulin levels were markedly decreased postoperatively at all time points (all P<.01). Insulin AUC decreased progressively throughout the first postoperative year (P = .04), whereas glucose AUC decreased significantly at 6 and 12 months postoperatively (both P<.01). Insulin sensitivity measured by the Matsuda index increased progressively postoperatively. First phase insulin secretion remained unchanged. Conclusion: Postprandial total GLP-1 and total PYY levels increased significantly at 6 weeks post-SG and remained elevated for at least 1 year. These findings may indicate their involvement in better glucose homeostasis and weight loss maintenance after SG. [Copyright &y& Elsevier]

Bariatric surgery remains the most effective treatment for severely obese patients. However, the potential long-term effects of bariatric surgical procedures on health, including bone health, are only partially understood. The goal of this review was to present data on the impact of bariatric surgery on bone metabolism and to analyse possible reasons for the loss of bone mass that frequently occurs after bariatric surgery. Such factors include nutritional deficiencies, rapid weight loss per se, effects of fat-derived adipokines and gut-derived appetite-regulatory hormones. However, the relative roles of these factors in skeletal regulation and the mechanisms by which they work are not yet fully defined. Our review was focussed on the complex relationship between body weight, fat mass and bone mass, as well as peripheral and central mediators potentially involved in the dual regulation of both energy and bone homeostasis. We also review the data on the inverse relationship between central obesity, bone marrow fat and osteoporosis. As the number of bariatric operations increases, it is imperative to recognize mechanisms responsible for bariatric surgery-induced bone loss, with careful monitoring of bone health including long-term fracture incidence in patients undergoing these procedures. [ABSTRACT FROM AUTHOR]

Vigorous running suppresses plasma acylated ghrelin concentrations but the limited literature on cycling suggests that acylated ghrelin is unchanged, perhaps because body mass is supported during cycling. It is important from a research and applied perspective to determine whether acylated ghrelin and hunger responses are exercise-mode specific. This study sought to examine this. Eleven recreationally active males fasted overnight and completed three 4-h trials: control, running, and cycling, in a random order. Participants rested throughout the control trial and ran or cycled at 70% of mode-specific maximal oxygen uptake for the first hour during exercise trials, resting thereafter. Hunger was measured every 0.5 h using visual analogue scales. Eight venous blood samples were collected to determine acylated ghrelin concentrations and a standardised meal was consumed at 3 h. Compared with the control trial, acylated ghrelin concentrations were suppressed to a similar extent at 0.5 and 1 h during the running (p < 0.005) and cycling (p < 0.001) trials. Area under the curve values for ghrelin concentration over time were lower during exercise trials versus control (Control: 606 ± 379; Running: 455 ± 356; Cycling: 448 ± 315 pg⋅mL-1⋅4 h-1 ; mean ± SD, p < 0.05). Hunger values did not differ significantly between trials but an interaction effect (p < 0.05) indicated a tendency for hunger to be suppressed during exercise. Thus, at similar relative exercise intensities, plasma acylated ghrelin concentrations are suppressed to a similar extent during running and cycling. [ABSTRACT FROM AUTHOR]

Because of differential processing of the hormone precursor, proglucagon, numerous peptide products are released from the pancreatic alpha cells and the intestinal L-cells in which the (pro)glucagon gene is expressed. Of particular interest in relation to obesity are glucagon from the pancreas and oxyntomodulin and GLP-1 from the gut, all of which inhibit food intake, but the other products are also briefly discussed, because knowledge about these is required for selection and evaluation of the methods for measurement of the hormones. The distal intestinal L-cells also secrete the appetite-inhibiting hormone PYY. Characteristics of the secretion of the pancreatic and intestinal products are described, and causes of the hypersecretion of glucagon in obesity and type 2 diabetes are discussed. In contrast, the secretion of the products of the L-cells is generally impaired in obesity, raising questions about their role in the development of obesity. It is concluded that the impairment probably is secondary to obesity, but the lower plasma levels may contribute to the development., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Holst.)

Reproduction and metabolism are intricately linked. Gut hormones play key roles in the regulation of body weight and glucose homeostasis, factors that influence the functioning of the hypothalamic-pituitary-gonadal axis and reproductive outcomes. Data from rodent models suggest gut hormones may have direct stimulatory effects on reproductive hormone release. However, the effects of gut hormones on reproductive function in humans are more complex, with possible involvement of direct (e.g. via gut hormone receptor agonism) as well as indirect (e.g. via weight reduction in people with obesity) mechanisms. The use of gut hormone receptor agonists has become an integral part of the management of metabolic diseases (including obesity and type 2 diabetes), with additional indications for their use on the horizon. Future work may identify specific roles for gut hormone receptor agonists in the treatment of reproductive co-morbidities that are increasingly being recognised in people with metabolic diseases., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Aim: To assess the impact of the sodium-glucose co-transporter-2 (SGLT2) inhibitor empagliflozin (25 mg once-daily), dietary energy restriction, or both combined, on circulating appetite-regulatory peptides in people with type 2 diabetes (T2D) and overweight or obesity., Materials and Methods: In a double-blind, placebo-controlled trial, 68 adults (aged 30-75 years) with T2D (drug naïve or on metformin monotherapy; HbA1c 6.0%-10.0% [42-86 mmol/mol]) and body mass index of 25 kg/m 2 or higher were randomized to (a) placebo only, (b) placebo plus diet, (c) empagliflozin only or (d) empagliflozin plus diet for 24 weeks. Dietary energy restriction matched the estimated energy deficit elicited by SGLT2 inhibitor therapy through urinary glucose excretion (~360 kcal/day). The primary outcome was change in postprandial circulating total peptide-YY (PYY) during a 3-hour mixed-meal tolerance test from baseline to 24 weeks. Postprandial total glucagon-like peptide-1 (GLP-1), acylated ghrelin and subjective appetite perceptions formed secondary outcomes, along with other key components of energy balance., Results: The mean weight loss in each group at 24 weeks was 0.44, 1.91, 2.22 and 5.74 kg, respectively. The change from baseline to 24 weeks in postprandial total PYY was similar between experimental groups and placebo only (mean difference [95% CI]: -8.6 [-28.6 to 11.4], 13.4 [-6.1 to 33.0] and 1.0 [-18.0 to 19.9] pg/ml in placebo-plus diet, empagliflozin-only and empagliflozin-plus-diet groups, respectively [all P ≥ .18]). Similarly, there was no consistent pattern of difference between groups for postprandial total GLP-1, acylated ghrelin and subjective appetite perceptions., Conclusions: In people with T2D and overweight or obesity, changes in postprandial appetite-regulatory gut peptides may not underpin the less than predicted weight loss observed with empagliflozin therapy., Clinical Trials Registration: NCT02798744, www., Clinicaltrials: gov; 2015-001594-40, www.EudraCT.ema.europa.eu; ISRCTN82062639, www.ISRCTN.org., (© 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Objective: Although gut dysbiosis is increasingly recognised as a pathophysiological component of metabolic syndrome (MetS), the role and mode of action of specific gut microbes in metabolic health remain elusive. Previously, we identified the commensal butyrogenic Anaerobutyricum soehngenii to be associated with improved insulin sensitivity in subjects with MetS. In this proof-of-concept study, we investigated the potential therapeutic effects of A. soehngenii L2-7 on systemic metabolic responses and duodenal transcriptome profiles in individuals with MetS., Design: In this randomised double-blind placebo-controlled cross-over study, 12 male subjects with MetS received duodenal infusions of A. soehngenii / placebo and underwent duodenal biopsies, mixed meal tests (6 hours postinfusion) and 24-hour continuous glucose monitoring., Results: A. soehngenii treatment provoked a markedly increased postprandial excursion of the insulinotropic hormone glucagon-like peptide 1 (GLP-1) and an elevation of plasma secondary bile acids, which were positively associated with GLP-1 levels. Moreover, A. soehngenii treatment robustly shaped the duodenal expression of 73 genes, with the highest fold induction in the expression of regenerating islet-protein 1B ( REG1B )-encoding gene. Strikingly, duodenal REG1B expression positively correlated with GLP-1 levels and negatively correlated with peripheral glucose variability, which was significantly diminished in the 24 hours following A. soehngenii intake. Mechanistically, Reg1B expression is induced upon sensing butyrate or bacterial peptidoglycan. Importantly, A. soehngenii duodenal administration was safe and well tolerated., Conclusions: A single dose of A. soehngenii improves peripheral glycaemic control within 24 hours; it specifically stimulates intestinal GLP-1 production and REG1B expression. Further studies are needed to delineate the specific pathways involved in REG1B induction and function in insulin sensitivity., Trial Registration Number: NTR-NL6630., Competing Interests: Competing interests: MN is in the scientific board of Kaleido Biosciences, Boston USA. WMDV is founder and in the board of A-mansia, Belgium. FB is in the scientific board of Metabogen AB, Sweden. MN and WMDV are founders and Scientific Advisory Board members of Caelus Pharmaceuticals, the Netherlands. SLH is a paid consultant for P&G and coinventor on pending and issued patents held by the Cleveland Clinic, and is eligible for receiving payments for inventions or discoveries related to cardiovascular diagnostics or therapeutics from Cleveland HeartLab, Quest Diagnostics and P&G., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Despite decades of obesity research and various public health initiatives, obesity remains a major public health concern. Our most drastic but most effective treatment of obesity is bariatric surgery with weight loss and improvements in co-morbidities, including resolution of type 2 diabetes (T2D). However, the mechanisms by which surgery elicits metabolic benefits are still not well understood. One proposed mechanism is through signals generated by the intestine (nutrients, neuronal, and/or endocrine) that communicate nutrient status to the brain. In this review, we discuss the contributions of gut-brain communication to the physiological regulation of body weight and its impact on the success of bariatric surgery. Advancing our understanding of the mechanisms that drive bariatric surgery-induced metabolic benefits will ultimately lead to the identification of novel, less invasive strategies to treat obesity., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: In patients with type 2 diabetes mellitus (T2DM), Roux-en-Y gastric bypass (RYGB) leads to beneficial metabolic adaptations, including enhanced incretin secretion, beta-cell function, and systemic insulin sensitivity. We explored the impact of RYGB on pituitary, pancreatic, gut hormones, and cortisol responses to parenteral and enteral nutrient stimulation in patients with obesity and T2DM with repeated sampling up to 2 years after intervention., Methods: We performed exploratory post hoc analyses in a previously reported randomized trial. Levels of adrenocorticotropic hormone (ACTH), cortisol, growth hormone (GH), glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), peptide YY (PYY), ACTH, insulin, and glucagon were measured in 13 patients with T2DM and obesity at four different visits: before and 4, 24, and 104 weeks after RYGB; and in three sequential conditions on the same day: fasting, intravenous arginine challenge, and OGTT., Results: RYGB surprisingly induced a rise in ACTH, cortisol, and GH levels upon an oral glucose load, together with enhanced GLP-1 and PYY responses. Fasting and post-arginine GH levels were higher after RYGB, whereas insulin, glucagon, GLP-1, GIP, and cortisol were lower. These endocrine adaptations were seen as early as 4 weeks after surgery and were maintained for up to 2 years., Conclusion: These findings indicate adaptations of glucose sensing mechanisms and responses in multiple endocrine organs after RYGB, involving the gut, pancreatic islets, the pituitary gland, the adrenals, and the brain.

Background: Plausible phenotype mechanisms following bariatric surgery include changes in neural and gastrointestinal physiology. This pilot study aims to investigate individual and combined neurologic, gut microbiome, and plasma hormone changes pre- versus post-vertical sleeve gastrectomy (VSG), Roux-en-Y gastric bypass (RYGB), and medical weight loss (MWL). We hypothesized post-weight loss phenotype would be associated with changes in central reward system brain connectivity, differences in postprandial gut hormone responses, and increased gut microbiome diversity., Methods: Subjects included participants undergoing VSG, n = 7; RYGB, n = 9; and MWL, n = 6. Ghrelin, glucagon-like peptide-1, peptide-YY, gut microbiome, and resting state functional magnetic resonance imaging (rsfMRI; using fractional amplitude of low-frequency fluctuations [fALFF]) were measured pre- and post-intervention in fasting and fed states. We explored phenotype characterization using clustering on gut hormone, microbiome, and rsfMRI datasets and a combined analysis., Results: We observed more widespread fALFF differences post-bariatric surgery versus post-MWL. Decreased post-prandial fALFF was seen in food reward regions post-RYGB. The highest number of microbial taxa that increased post-intervention occurred in the RYGB group, followed by VSG and MWL. The combined hormone, microbiome, and MRI dataset most accurately clustered samples into pre- versus post-VSG phenotypes followed by RYGB subjects., Conclusion: The data suggest surgical weight loss (VSG and RYGB) has a bigger impact on brain and gut function versus MWL and leads to lesser post-prandial activation of food-related neural circuits. VSG subjects had the greatest phenotype differences in interactions of microbiome, rsfMRI, and gut hormone features, followed by RYGB and MWL. These results will inform future prospective research studying gut-brain changes post-bariatric surgery.

Short-chain fatty acids (SCFA) can regulate appetite by stimulating the secretion of satiety hormones. However, the impact of short-chain fatty acid propionate on the release of gut satiety hormones and appetite regulation in pigs is not completely understood. In this study, 16 pigs were infused with saline or sodium propionate through a fistula in the caecum during a 28-day experimental period. We characterized the effects of propionate administration on peptide YY (PYY) and glucagon-like peptide 1 (GLP-1) secretion from colonic tissue, and investigated the role of propionate infusion on the expression of appetite-related genes in the colon and hypothalamus. Further, the direct impact of propionate administration on the expression of orexigenic neuropeptide agouti-related protein ( AgRP ) in hypothalamic N38 cells was also examined. The results showed that intra-cecal infusion of propionate reduced the short-term feed intake ( P  < 0.05) but not the long-term feed intake in pigs ( P  > 0.05). Propionate administration stimulated PYY and GLP-1 release from colon tissue in vivo and ex vivo ( P  < 0.05). It also upregulated PYY expression in the colonic mucosa ( P  < 0.05). Meanwhile, the GLP-1 and PYY levels in the blood were increased after intra-cecal infusion of propionate at d 28 ( P  < 0.05). Additionally, intra-cecal infusion of propionate upregulated the mRNA and protein expression of free fatty acid receptor 2/3 (FFAR2/FFAR3) in the colonic mucosa ( P  < 0.05). Propionate infusion also downregulated the orexigenic AgRP mRNA expression ( P  < 0.05) and upregulated the anorexigenic cocaine-and amphetamine-regulated transcript ( CART ) mRNA expression ( P  = 0.09) in the hypothalamus. Moreover, propionate administration directly downregulated AgRP expression in hypothalamic N38 cells in a dose-dependent manner ( P  < 0.05). Collectively, these findings demonstrated that cecal propionate stimulated colonic secretion of satiety hormones and suppressed appetite to reduce the short-term feed intake in pigs. This study highlights that microbial-derived propionate exerts an important role in regulating the physical functions of the host., Competing Interests: We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, and there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the content of this paper., (© 2022 Chinese Association of Animal Science and Veterinary Medicine. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)

Obesity is a major worldwide health problem. The treatment options are severely limited. The development of novel anti-obesity drugs is fraught with efficacy and safety issues. Consequently, several investigational anti-obesity drugs have failed to gain marketing approval in recent years. Anorectic gut hormones offer a potentially safe and viable option for the treatment of obesity. The prospective utility of gut hormones has improved drastically in recent years with the development of longer acting analogues. Additionally, specific combinations of gut hormones have been demonstrated to have additive anorectic effects. This article reviews the current stage of anti-obesity drugs in development, focusing on gut hormone-based therapies. [ABSTRACT FROM AUTHOR]

Abstract: The gut–brain axis refers to the bidirectional communication between the gut and the brain. Four information carriers (vagal and spinal afferent neurons, immune mediators such as cytokines, gut hormones and gut microbiota-derived signalling molecules) transmit information from the gut to the brain, while autonomic neurons and neuroendocrine factors carry outputs from the brain to the gut. The members of the neuropeptide Y (NPY) family of biologically active peptides, NPY, peptide YY (PYY) and pancreatic polypeptide (PP), are expressed by cell systems at distinct levels of the gut–brain axis. PYY and PP are exclusively expressed by endocrine cells of the digestive system, whereas NPY is found at all levels of the gut–brain and brain–gut axis. The major systems expressing NPY comprise enteric neurons, primary afferent neurons, several neuronal pathways throughout the brain and sympathetic neurons. In the digestive tract, NPY and PYY inhibit gastrointestinal motility and electrolyte secretion and in this way modify the input to the brain. PYY is also influenced by the intestinal microbiota, and NPY exerts, via stimulation of Y1 receptors, a proinflammatory action. Furthermore, the NPY system protects against distinct behavioural disturbances caused by peripheral immune challenge, ameliorating the acute sickness response and preventing long-term depression. At the level of the afferent system, NPY inhibits nociceptive input from the periphery to the spinal cord and brainstem. In the brain, NPY and its receptors (Y1, Y2, Y4, Y5) play important roles in regulating food intake, energy homeostasis, anxiety, mood and stress resilience. In addition, PP and PYY signal to the brain to attenuate food intake, anxiety and depression-related behaviour. These findings underscore the important role of the NPY-Y receptor system at several levels of the gut–brain axis in which NPY, PYY and PP operate both as neural and endocrine messengers. [Copyright &y& Elsevier]

The long-term effects of lifestyle changes, diet and medical therapy on obesity are limited. Bariatric surgery is the most effective long-term treatment with the greatest chances for amelioration of obesity-associated complications, including type 2 diabetes mellitus (T2DM). There is increasing evidence in the literature that bariatric operations have a profound effect on human physiology, by reducing hunger, increasing satiety, paradoxically increasing energy expenditure, and even promoting healthy food preferences. Some of these operations improve glucose homeostasis in patients with T2DM independently of weight loss. Changes in the gut hormone levels of glucagon-like peptide 1, peptide YY and ghrelin have been proposed as some of the mediators implicated in changing physiology. The aim of this review is to critically explore the current knowledge on the putative mechanisms of the change in weight and improvement in T2DM glycaemic control after the most commonly performed bariatric operations. [ABSTRACT FROM AUTHOR]

The nutritional status in patients in ITU appears to decline not only during their stay in ITU but long after discharge from ITU. The deterioration in nutritional status during and after ITU management is not fully understood. Re-establishing normal spontaneous feeding after critical illness is a vital component in the recuperative process. Gut released peptides, such as ghrelin and peptide YY (PYY) that regulate the initiation and termination of meals (Cummings et al. 2002, Batterham et al. 2002), could play a role in the altered eating behaviour patients. The aim of this study was to assess the pattern of ghrelin and PYY during the stay of ITU patients in hospital. 16 patients aged 60± 4.7yrs, BMI 28.1± 1.7kg/m2 (mean± SEM) admitted to ITU underwent fasting blood sample collections every second day throughout the first week on ITU and once a week thereafter until day 28 or discharge home. Changes in appetite, biochemical and anthropometric markers of nutritional status were recorded. Three fasting blood samples at least three days apart were collected from the 36 matched age and BMI healthy volunteers 54.3±2.9yrs, p=0.3 BMI 25.8±0.8kg/m2 P=0.2. As compared with healthy subjects, ITU patients exhibited a significantly lower level of ghrelin (day one 297±76.3 v. 919.8±88.3 pmol/l P

Background: Laparoscopic Roux-en Y-Gastric bypass (LRYGBP) is the commonest available option for the surgical treatment of morbid obesity. Weight loss following bariatric surgery has been linked to changes of gastrointestinal peptides, shown to be implicated also in metabolic effects and appetite control. The purpose of this study was to evaluate whether gastric fundus resection in patients undergoing LRYGBP enhances the efficacy of the procedure in terms of weight loss, glucose levels, and hormonal secretion. Methods: Twelve patients underwent LRYGBP and 12 patients LRYGBP plus gastric fundus resection (LRYGBP+FR). All patients were evaluated before and at 3, 6, and 12 months postoperatively. Blood samples were collected after an overnight fast and 30, 60, and 120 min after a standard 300-kcal mixed meal. Results: Body weight and body mass index decreased markedly and comparably after both procedures. Fasting ghrelin decreased 3 months after LRYGBP, but increased at 12 months to levels higher than baseline while after LRYGBP+FR was markedly and persistently decreased. Postprandial GLP-1, PYY, and insulin responses were enhanced more and postprandial glucose levels were lower after LRYGBP+FR compared to LRYGBP. Postoperatively, ghrelin changes correlated negatively with GLP-1 changes. Conclusions: Resection of the gastric fundus in patients undergoing LRYGBP was associated with persistently lower fasting ghrelin levels; higher postprandial PYY, GLP-1, and insulin responses; and lower postprandial glucose levels compared to LRYGBP. These findings suggest that fundus resection in the setting of LRYGBP may be more effective than RYGBP for the management of morbid obesity and diabetes type 2. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The aim of our study was to evaluate the effect of a lifestyle intervention program on β-cell function and to explore the role of gastrointestinal peptides in subjects with T2D. Methods: Subjects with T2D (n=74) received 24weeks of intervention: 12weeks of slimming diet (−500kcal/day) and the subsequent 12weeks of diet were combined with aerobic exercise. All subjects were examined at weeks 0, 12 and 24. β-cell function was assessed during standard meal tests. Insulin secretory rate (ISR) was calculated by C-peptide deconvolution, and β-cell function was quantified with a mathematical model. Plasma concentrations of gastrointestinal peptides were measured in a fasting state and during hyperinsulinemia induced by hyperinsulinemic isoglycemic clamp. Results: Mean weight loss was 5.03±4.38kg (p<0.001) in weeks 0–12. Weight did not change significantly in weeks 12–24. Both insulin secretion at the reference level and glucose sensitivity increased in weeks 0–12 (by 33%±54% and by 26%±53%, respectively, p<0.001) and remained unchanged in weeks 12–24. Both fasting and hyperinsulinemic plasma concentrations of pancreatic polypeptide (PP) decreased in weeks 0–12 (p<0.05 for both) and did not change significantly in weeks 12–24. Changes in insulin secretion at the reference level correlated negatively with plasma concentrations of PP during hyperinsulinemia (r=−0.36; p<0.001). Changes in glucose sensitivity correlated negatively with changes in plasma concentrations of PP, both in fasting and during hyperinsulinemia (r=−0.2; p=0.01 for both). The correlations remained significant after adjustment for changes in body-mass-index. Conclusions: After diet-induced weight loss, β-cell function improved in T2D subjects and remained unchanged after the addition of exercise. We demonstrate for the first time that these changes are associated with a decrease in PP secretion. [Copyright &y& Elsevier]

Abstract: Background: The reported remission of type 2 diabetes in patients undergoing Roux-en-Y gastric bypass has brought the role of the gut in glucose metabolism into focus. Our objective was to explore the differential effects on glucose homeostasis after oral versus gastrostomy glucose loading in patients with Roux-en-Y gastric bypass at an academic health science center. Methods: A comparative controlled investigation of oral versus gastrostomy glucose loading in 5 patients who had previously undergone gastric bypass and had a gastrostomy tube placed in the gastric remnant for feeding. A standard glucose load was administered either orally (day 1) or by the gastrostomy tube (day 2). The plasma levels of glucose, insulin, glucagon-like peptide 1 and peptide YY were measured before and after glucose loading. Results: Exclusion of the proximal small bowel from glucose passage induced greater plasma insulin, glucagon-like peptide 1, and peptide YY responses compared with glucose loading by way of the gastrostomy tube (P <.05). Conclusions: Exclusion of glucose passage through the proximal small bowel results in enhanced insulin and gut hormone responses in patients after gastric bypass. The gut plays a central role in glucose metabolism and represents a target for future antidiabetes therapies. [Copyright &y& Elsevier]

Background: Laparoscopic Roux-en-Y gastric bypass (LRYGB) is the most common bariatric technique. Laparoscopic sleeve gastrectomy (LSG) is a restrictive procedure; the metabolic and endocrine effects of which remain unknown. We compared the effects of both procedures on glucose metabolism and fasting and meal-stimulated gut hormone levels. Methods: Seven patients were randomised to LRYGB and eight to LSG. All patients were evaluated before and at 3 and 12 months postoperatively. Plasma levels of glucose, insulin, ghrelin, leptin, peptide YY (PYY), GLP-1 and pancreatic polypeptide were measured before and after 10 and 60 min of a standard test meal ingestion. Results: Age, body mass index and preoperative hormone levels were similar in both groups. A significant reduction of plasma glucose and insulin levels was observed after surgery. Moreover, a normalisation of homeostatic model assessment for insulin resistance value was also seen after both procedures. The fasting and postprandial leptin levels were significantly lower in the LRYGB group. LSG was followed by a significant reduction in fasting ghrelin levels. In the LRYGB group, GLP-1 levels increased significantly after the test meal. Conclusions: LRYGB and LSG markedly improved glucose homeostasis. Only LSG decreased fasting and postprandial ghrelin levels, whereas GLP-1 and PYY levels increased similarly after both procedures. [ABSTRACT FROM AUTHOR]

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are incretins produced in the intestine that play a central role in glucose metabolism and insulin secretion. Circulating concentrations of GLP-1 and GIP are low and can be difficult to assay in rodents. These studies utilized the novel intestinal lymph fistula model we have established to investigate the mechanism of lipid-stimulated incretin secretion. Peak concentrations of GLP-1 and GIP following an enteral lipid stimulus (Liposyn) were significantly higher in intestinal lymph than portal venous plasma. To determine whether lipid-stimulated incretin secretion was related to chylomicron formation Pluronic L-81 (L-81), a surfactant inhibiting chylomicron synthesis, was given concurrently with Liposyn. The presence of L-81 almost completely abolished the increase in lymph triglyceride seen with Liposyn alone ( P < 0.001). Inhibition of chylomicron formation with L-81 reduced GLP-1 secretion into lymph compared to Liposyn stimulation alone ( P = 0.034). The effect of L-81 relative to Liposyn alone had an even greater effect on GIP secretion, which was completely abolished ( P = 0.004). These findings of a dramatic effect of L-81 on lymph levels of GLP-1 and GIP support a strong link between intestinal lipid absorption and incretin secretion. The relative difference in the effect of L-81 on the two incretins provides further support that nutrient-stimulation of GIP and GLP-1 is via distinct mechanisms. [ABSTRACT FROM AUTHOR]

Background: The mechanisms of amelioration of glycemic control early after laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) are not fully understood. Methods: In this prospective, randomized 1-year trial, outcomes of LRYGB and LSG patients were compared, focusing on possibly responsible mechanisms. Twelve patients were randomized to LRYGB and 11 to LSG. These non-diabetic patients were investigated before and 1 week, 3 months, and 12 months after surgery. A standard test meal was given after an overnight fast, and blood samples were collected before, during, and after food intake for hormone profiles (cholecystokinin (CCK), ghrelin, glucagon-like peptide 1 (GLP-1), peptide YY (PYY)). Results: In both groups, body weight and BMI decreased markedly and comparably leading to an identical improvement of abnormal glycemic control (HOMA index). Post-surgery, patients had markedly increased postprandial plasma GLP-1 and PYY levels ( p < 0.05) with ensuing improvement in glucose homeostasis. At 12 months, LRYGB ghrelin levels approached preoperative values. The postprandial, physiologic fluctuation returned, however, while LSG ghrelin levels were still markedly attenuated. One year postoperatively, CCK concentrations after test meals increased less in the LRYGB group than they did in the LSG group, with the latter showing significantly higher maximal CCK concentrations ( p < 0.012 vs. LRYGB). Conclusions: Bypassing the foregut is not the only mechanism responsible for improved glucose homeostasis. The balance between foregut (ghrelin, CCK) and hindgut (GLP-1, PYY) hormones is a key to understanding the underlying mechanisms. [ABSTRACT FROM AUTHOR]

While bariatric procedures continued to evolve and develop since the 1950s, their classification has not matched this evolution. The procedures are commonly classified into restrictive, malabsorptive, or combined. In this day and age, we recognize different mechanisms of action of the bariatric procedures. This article aims to review and update the old classifications based on our current understanding of the hormonal aspects of the various bariatric procedures and the role of gut hormones in weight loss and treatment of the associated metabolic comorbidities. The article suggests the need for a new classification of the bariatric procedures, based on the mechanism of action, involving the hormonal aspects of the procedure. [ABSTRACT FROM AUTHOR]

Metabolism is controlled through homeostatic system consisting of central centers, gut hormones, hormones from adipose tissue and the other hormonal axes. This cooperation is based on cross-talk between central and peripheral signals. Among them the hypothalamus plays a crucial role, with interconnected nuclei forming neuronal circuits. Other regions in the brain, such as the brain stem, the endocannabinoid system, the vagal afferents, are also involved in energy balance. The second component is peripheral source of signals − the gastrointestinal tract hormones. Additionally, adipokines from adipose tissue, thyrotropic, gonadotropic and somatotropic axes play a role in energy homeostasis. Knowledge about all components of this neuroendocrine circuit will be helpful in developing novel therapeutic approaches against the metabolic syndrome and its components. [ABSTRACT FROM AUTHOR]

Obesity remains a major worldwide health problem, with current medical treatments being poorly effective. Nutrient sensing allows organs such as the GI tract and the brain to recognize and respond to fuel substrates such as carbohydrates, protein and fats. Specialized neural and hormonal pathways exist to facilitate and regulate these chemosensory mechanisms. Manipulation of factors involved in either central or peripheral chemosensory pathways may provide possible targets for the manipulation of appetite. However, further research is required to assess the utility of this approach to developing novel anti-obesity agents. INSET: Key issues. [ABSTRACT FROM AUTHOR]

Abstract: Tyrosyl O-sulfation is a common posttranslational derivatization of proteins that may also modify regulatory peptides. Among these are members of the cholecystokinin (CCK)/gastrin family. While sulfation of gastrin peptides is without effect on the bioactivity, O-sulfation is crucial for the cholecystokinetic activity (i.e. gallbladder emptying) of CCK peptides. Accordingly, the purification of CCK as a sulfated peptide was originally monitored by its gallbladder emptying effect. Since then, the dogma has prevailed that CCK peptides are always sulfated. The dogma is correct in a semantic context since the gallbladder expresses only the CCK-A receptor that requires sulfation of the ligand. CCK peptides, however, are also ligands for the CCK-B receptors that do not require ligand sulfation. Consequently, unsulfated CCK peptides may act via CCK-B receptors. Since in vivo occurrence of unsulfated products of proCCK with an intact α-amidated C-terminal tetrapeptide sequence (–Trp-Met-Asp-PheNH2) has been reported, it is likely that unsulfated CCK peptides constitute a separate hormone system that acts via CCK-B receptors. This review discusses the occurrence, molecular forms, and possible physiological as well as pathophysiological significance of unsulfated CCK peptides. [Copyright &y& Elsevier]

Abstract: Exposure to high temperatures during the summer renders pigs susceptible to severe heat stress. Our previous studies found that pig small intestine epithelial tissue became significantly damaged following exposure to heat stress, negatively affecting body weight gain. The deleterious effects of heat stress could be ameliorated using a traditional Chinese medicine decoction (CMD), sustaining normal growth while under heat stress. In the current study, we hypothesized the mechanism of CMD activity to be via regulation of gut hormones (NPY, MLN, SCT and GCG) secretion from endocrine cells, which are responsible for nutrient digestion and absorption. To test this, 36 Chinese experimental mini-pigs (2months of age) were screened according to weight and litter origin, and divided into three treatment groups: control (23°C for 24h+standard feed), heat stress (HS; 26°C for 19h, 40°C for 5h+standard feed) and CMD (26°C for 19h, 40°C for 5h+standard feed supplemented with CMD); n=12 per group. Feed intake and body weight gain were measured daily. Pigs were euthanized at days 1 and 6 after initial treatment with blood and sections of small intestine epithelial tissue collected. Serum cortisol (Cor) concentrations were determined using RIA. Endocrine cell number and structural analysis were performed using silver staining, and gut hormone secretion examined by microarray. Dietary supplementation with CMD significantly improved porcine growth performance (P <0.05), decreased the Cor levels (P <0.01), increased endocrine cell number as well as up-regulating neuropeptide Y (NPY), motilin (MLN) and secretin (SCT) and down-regulating glucagon (GCG) expression in pig jejunum on day 6 when compared with the HS group. Taken together, our results indicate CMD supplementation can significantly reduce the negative effects of heat stress on pig jejunum, maintaining growth performance similar to non-heat stressed animals. CMD''s activity appears to be via adjusting gut hormone secretion to regulate metabolism and improve animal growth. [Copyright &y& Elsevier]

Background: Unknown hormonal and neural satiety signals are thought to drive sustainable weight loss following laparoscopic adjustable gastric banding (LAGB). The objective of this study was to investigate whether the structurally related satiety hormones pancreatic polypeptide (PP) and peptide YY (PYY) influence total percentage weight loss after LAGB. Methods: A cross-sectional study examined 17 postoperative individuals who had already achieved a mean of 28% LAGB-induced weight loss (range, 10-38%). A prospective study assessed plasma PP and PYY meal responses in 16 obese individuals prior to LAGB. Results: In the cross-sectional study, individuals with higher weight loss had lower PP meal responses (2-h AUC, R = −0.60, p = 0.01) and lower fasting PYY levels ( R = −0.55, p = 0.02). In the prospective study, subsequent mean weight loss was 20% (range, 5-50%) after a mean of 53 months. Low preoperative PP meal response (2-h AUC) predicted significantly higher subsequent weight loss after LAGB ( R = −0.56, p = 0.024). The eight individuals with the lowest PP meal response lost more weight than the eight with the highest PP meal response (median 25% vs. 14%, p = 0.004). When compared across all three groups, mean PP meal responses did not differ. Fasting PYY levels, however, were significantly lower in the postoperative group compared to the group tested pre-operatively, or the BMI-matched controls (−30%, p = 0.03). Conclusions: PYY appears reduced in proportion to weight loss following LAGB, possibly representing attempted orexigenic homeostatic compensation. Although PP responses appear unchanged by weight loss status, low PP meal response may predict higher weight loss. PP meal response may be a biological marker that could predict an individual's susceptibility to the mechanism underlying LAGB-induced weight loss. [ABSTRACT FROM AUTHOR]

Abstract: Gastrointestinal (GI) motility and gut hormones have been considered to be involved in the development and maintenance of obesity. Our aim was to assess the relationships between gastric emptying (GE), GI transit and gut hormones and leptin concentrations in diet-induced obese rat model. Male 6-week-old Sprague–Dawley rats were fed with a high-fat (HF) diet for 8weeks to generate diet-induced obesity (DIO) and diet resistant (DR) rats. GE, GI transit and plasma ghrelin, cholecystokinin (CCK), PYY and leptin concentrations were determined in DIO, DR and control (CON) rats. The DIO rats had slower GE, higher plasma leptin and CCK concentrations, and lower plasma ghrelin concentration compared with CON and DR rats. GE was correlated with plasma ghrelin (r =0.402, P =0.028), CCK (r =−0.518, P =0.003) and leptin concentration (r =−0.514, P =0.004). The slower GE, which can be considered as an adaptive response aimed at HF diet induced obesity, may be mediated by changes of plasma ghrelin, CCK and leptin concentrations. [Copyright &y& Elsevier]

Abstract: Roux-en-Y gastric bypass (gastric bypass) patients reportedly have changes in perception and consumption of sweet-tasting foods. This study aimed to further investigate alterations in sweet food intake in rats and sucrose detection in humans after gastric bypass. Wistar rats were randomized to gastric bypass or sham-operations and preference for sucrose (sweet), sodium chloride (salty), citric acid (sour) and quinine hydrochloride (bitter) was assessed with standard two-bottle intake tests (vs. water). Intestinal T1R2 and T1R3 expression and plasma levels of glucagon-like-peptide 1 (GLP-1) and peptide YY (PYY) were measured. Furthermore, obese patients and normal weight controls were tested for sucrose taste detection thresholds pre- and postoperatively. Visual analogue scales measuring hedonic perception were used to determine the sucrose concentration considered by patients and controls as “just about right” pre- and postoperatively. Gastric bypass reduced the sucrose intake relative to water in rats (p<0.001). Preoperative sucrose exposure reduced this effect. Preference or aversion for compounds representative of other taste qualities in naïve rats remained unaffected. Intestinal T1R2 and T1R3 expression was significantly decreased in the alimentary limb while plasma levels of GLP-1 and PYY were elevated after bypass in rats (p=0.01). Bypass patients showed increased taste sensitivity to low sucrose concentrations compared with controls (p<0.05), but both groups considered the same sucrose concentration as “just about right” postoperatively. In conclusion, gastric bypass reduces sucrose intake relative to water in sucrose-naïve rats, but preoperative sucrose experience attenuates this effect. Changes in sucrose taste detection do not predict hedonic taste ratings of sucrose in bypass patients which remain unchanged. Thus, factors other than the unconditional affective value of the taste may also play a role in determining food preferences after gastric bypass. [Copyright &y& Elsevier]

Introduction: In the almost six decades of bariatric surgery, a variety of surgical approaches to treating morbid obesity have been developed. History and evolution: Rather than prior techniques being continually superseded by new ones, a broad choice of surgical solutions based on restrictive, malabsorptive, humoral effects, or combinations thereof, is now available. In fact, in recent years, the advent of surgically modifying human metabolism promises new approaches to ameliorate traditionally medically treated metabolic entities, i.e., diabetes, even in the non-obese. The understanding of the various metabolic effects have led to a paradigm shift from bariatric surgery as a solely weight-reducing procedure to metabolic surgery affecting whole body metabolism. Conclusion: The bariatric surgeon now faces the challenge and opportunity of selecting the most suitable technique for each individual case. To assist in such decision-making, this review, Metabolic surgery-principles and current concepts, is presented, tracing the historical development; describing the various surgical techniques; elucidating the mechanisms by which glycemic control can be achieved that involve favorable changes in insulin secretion and insulin sensitivity, gut hormones, adipokines, energy expenditure, appetite, and preference for low glycemic index foods; as well as exploring the fascinating future potential of this new interdisciplinary field. [ABSTRACT FROM AUTHOR]