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1.
Am J Clin Nutr ; 111(6): 1137-1149, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32320002

RESUMO

BACKGROUND: Longer oral processing decreases food intake. This can be attributed to greater oro-sensory exposure (OSE) and a lower eating rate (ER). How these factors contribute to food intake, and the underlying physiological mechanisms, remain unclear. OBJECTIVES: We aimed to determine the independent and simultaneous effects of OSE and ER on satiation and associated endocrine responses. METHODS: Forty participants in study 1 [mean ± SD age: 24 ± 4 y; BMI (in kg/m2): 22 ± 2] and 20 in study 2 (mean ± SD age: 23 ± 3 y; BMI: 23 ± 2) participated in a 2 × 2 randomized trial. In both studies, participants ate chocolate custard with added caramel sauce (low OSE) or caramel fudge (high OSE) and with short (fast ER) or long breaks (slow ER) in between bites, until fullness. In study 2, endocrine responses were measured during the meal. RESULTS: In study 1, participants ate (mean ± SEM) 42 ± 15 g less in the slow- than in the fast-ER condition, only within the high-OSE condition (P = 0.04). In study 2, participants ate 66 ± 21 g less in the high- than in the low-OSE condition and there were no intake differences between slow and fast ER (P = 0.35). Eight minutes after starting to eat, insulin concentrations increased by 42%-65% in all treatments compared with the control. At the end of the meal, insulin concentrations were 81% higher in the high-OSE, slow-ER than in the low-OSE, fast-ER condition (P = 0.049). Pancreatic polypeptide (PP) increased by 62%, 5 min after meal onset in the low-OSE, fast-ER condition (P = 0.005). Ghrelin concentrations did not change. CONCLUSIONS: Greater OSE increases insulin responsiveness. In contrast, PP responses are stronger when OSE is reduced and ER is fast. Insulin and PP responses may mediate the independent effects of OSE and ER on food intake. These may be beneficial eating strategies, particularly for type 2 diabetic patients, to control food intake and maintain glucose homeostasis.This trial was registered at trialregister.nl as NL6544.


Assuntos
Ingestão de Alimentos , Grelina/metabolismo , Insulina/metabolismo , Peptídeo YY/metabolismo , Saciação , Adulto , Apetite , Comportamento Alimentar , Feminino , Humanos , Masculino , Boca/fisiologia , Adulto Jovem
2.
Endocr J ; 66(11): 943-952, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31564683

RESUMO

Malnutrition occurs when nutrient intake is too low for any reason and occurs regardless of gender or age. Therefore, besides loss of eating or digestive functionality due to illness, malnutrition can occur when a healthy individual undergoes an extreme diet and biases their nutrition, or when athletes exerts more energy than they can replenish through food. It has recently been reported that in Japan, the mortality rate of leaner individuals is equal to or higher than that of obese people. It is important to understand what homeostatic maintenance mechanism is behind this when the body is under hypotrophic conditions. Such mechanisms are generally endocranially controlled. We address this fundamental concern in this paper by focusing on peptide hormones. We introduce a mechanism for survival in a malnourished state via the regulation of food intake and temperature. Additionally, we will discuss the latest findings and future prospects for research on changes in the endocrine environment associated with malnutrition associated with exercise. We also review changes in next-generation endocrine environments when caused by malnutrition brought on by dieting.


Assuntos
Metabolismo Energético/fisiologia , Comportamento Alimentar/fisiologia , Desnutrição/metabolismo , Hormônios Peptídicos/metabolismo , Temperatura Corporal , Dieta Redutora , Ingestão de Energia , Epigênese Genética , Exercício Físico/fisiologia , Feminino , Grelina/metabolismo , Hormônio do Crescimento/metabolismo , Humanos , Insulina/metabolismo , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Leptina/metabolismo , Neuropeptídeo Y/metabolismo , Hormônios Peptídicos/genética , Peptídeo YY/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/genética , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Esportes , Termogênese
3.
Nutrients ; 11(9)2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31491982

RESUMO

Gut microbiota can influence the feeding behavior of the host, but the underlying mechanisms are unknown. Recently, caseinolytic protease B (ClpB), a disaggregation chaperon protein of Escherichia coli, was identified as a conformational mimetic of α-melanocyte-stimulating hormone (α-MSH), an anorexigenic neuropeptide. Importantly, ClpB was necessary for E. coli to have an anorexigenic effect in mice, suggesting that it may participate in satiety signaling. To explore this further, we determined the short-term (2 h) effects of three macronutrients: protein (bovine serum albumin), carbohydrate (D-fructose) and fat (oleic acid), on the production of ClpB by E. coli and analyzed whether ClpB can stimulate the secretion of the intestinal satiety hormone, peptide YY (PYY). Isocaloric amounts of all three macronutrients added to a continuous culture of E. coli increased ClpB immunoreactivity. However, to increase the levels of ClpB mRNA and ClpB protein in bacteria and supernatants, supplementation with protein was required. A nanomolar concentration of recombinant E. coli ClpB dose-dependently stimulated PYY secretion from the primary cell cultures of rat intestinal mucosa. Total proteins extracted from E. coli but not from ClpB-deficient E. coli strains also tended to increase PYY secretion. These data support a possible link between E. coli ClpB and protein-induced satiety signaling in the gut.


Assuntos
Endopeptidase Clp/metabolismo , Escherichia coli K12/enzimologia , Proteínas de Escherichia coli/metabolismo , Comportamento Alimentar , Microbioma Gastrointestinal , Proteínas de Choque Térmico/metabolismo , Mucosa Intestinal/microbiologia , Resposta de Saciedade , Animais , Células Cultivadas , Endopeptidase Clp/genética , Escherichia coli K12/efeitos dos fármacos , Escherichia coli K12/genética , Proteínas de Escherichia coli/genética , Frutose/farmacologia , Regulação Bacteriana da Expressão Gênica , Regulação Enzimológica da Expressão Gênica , Proteínas de Choque Térmico/genética , Interações Hospedeiro-Patógeno , Mucosa Intestinal/metabolismo , Masculino , Ácido Oleico/farmacologia , Peptídeo YY/metabolismo , Ratos Sprague-Dawley , Soroalbumina Bovina/farmacologia , Transdução de Sinais
4.
Animal ; 13(11): 2714-2726, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31387651

RESUMO

The gastrointestinal tract (GIT) is an interface between the external and internal milieus that requires continuous monitoring for nutrients or pathogens and toxic chemicals. The study of the physiological/molecular mechanisms, mediating the responses to the monitoring of the GIT contents, has been referred to as chemosensory science. While most of the progress in this area of research has been obtained in laboratory rodents and humans, significant steps forward have also been reported in pigs. The objective of this review was to update the current knowledge on nutrient chemosensing in pigs in light of recent advances in humans and laboratory rodents. A second objective relates to informing the existence of nutrient sensors with their functionality, particularly linked to the gut peptides relevant to the onset/offset of appetite. Several cell types of the intestinal epithelium such as Paneth, goblet, tuft and enteroendocrine cells (EECs) contain subsets of chemosensory receptors also found on the tongue as part of the taste system. In particular, EECs show specific co-expression patterns between nutrient sensors and/or transceptors (transport proteins with sensing functions) and anorexigenic hormones such as cholecystokinin (CCK), peptide tyrosine tyrosine (PYY) or glucagon-like peptide-1 (GLP-1), amongst others. In addition, the administration of bitter compounds has an inhibitory effect on GIT motility and on appetite through GLP-1-, CCK-, ghrelin- and PYY-labelled EECs in the human small intestine and colon. Furthermore, the mammalian chemosensory system is the target of some bacterial metabolites. Recent studies on the human microbiome have discovered that commensal bacteria have developed strategies to stimulate chemosensory receptors and trigger host cellular functions. Finally, the study of gene polymorphisms related to nutrient sensors explains differences in food choices, food intake and appetite between individuals.


Assuntos
Preferências Alimentares , Microbioma Gastrointestinal , Suínos/fisiologia , Animais , Apetite , Metabolismo dos Carboidratos , Colecistocinina/metabolismo , Células Enteroendócrinas/metabolismo , Trato Gastrointestinal/microbiologia , Trato Gastrointestinal/fisiologia , Grelina/metabolismo , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Nutrientes , Peptídeo YY/metabolismo , Suínos/microbiologia , Paladar
5.
Nutrients ; 11(7)2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31277416

RESUMO

Developing novel foods to suppress energy intake and promote negative energy balance and weight loss has been a long-term but commonly unsuccessful challenge. Targeting regulation of appetite is of interest to public health researchers and industry in the quest to develop 'functional' foods, but poor understanding of the underpinning mechanisms regulating food intake has hampered progress. The gastrointestinal (GI) or 'satiety' peptides including cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) secreted following a meal, have long been purported as predictive biomarkers of appetite response, including food intake. Whilst peptide infusion drives a clear change in hunger/fullness and eating behaviour, inducing GI-peptide secretion through diet may not, possibly due to modest effects of single meals on peptide levels. We conducted a review of 70 dietary preload (DIET) and peptide infusion (INFUSION) studies in lean healthy adults that reported outcomes of CCK, GLP-1 and PYY. DIET studies were acute preload interventions. INFUSION studies showed that minimum increase required to suppress ad libitum energy intake for CCK, GLP-1 and PYY was 3.6-, 4.0- and 3.1-fold, respectively, achieved through DIET in only 29%, 0% and 8% of interventions. Whether circulating 'thresholds' of peptide concentration likely required for behavioural change can be achieved through diet is questionable. As yet, no individual or group of peptides can be measured in blood to reliably predict feelings of hunger and food intake. Developing foods that successfully target enhanced secretion of GI-origin 'satiety' peptides for weight loss remains a significant challenge.


Assuntos
Regulação do Apetite , Ingestão de Alimentos , Metabolismo Energético , Comportamento Alimentar , Hormônios Peptídicos/metabolismo , Resposta de Saciedade , Perda de Peso , Fármacos Antiobesidade/administração & dosagem , Colecistocinina/metabolismo , Metabolismo Energético/efeitos dos fármacos , Feminino , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Humanos , Infusões Parenterais , Masculino , Hormônios Peptídicos/administração & dosagem , Peptídeo YY/metabolismo , Transdução de Sinais , Perda de Peso/efeitos dos fármacos
6.
Res Vet Sci ; 124: 223-227, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30928654

RESUMO

Gastrointestinal hormone based therapies are being investigated for treating diabetes in cats; however, the tissue distribution of these hormones and their cognate receptors remain largely understudied. We determined the distribution of transcripts for the gut hormones proglucagon (Gcg), glucose-dependent insulinotropic peptide (Gip), peptide YY (Pyy), and their receptors (Glp1r, Gipr, Npy2r), in feline peripheral tissues. The Gcg, Gip and Pyy mRNA were expressed in the gut, with higher Gcg and Pyy abundance in the lower gut. Interestingly, Glp1r and Npy2r mRNA were expressed in multiple peripheral tissues including the gut, pancreas and liver, whereas, Gipr mRNA was restricted to the stomach and adipose tissues. The localized mRNA expression of Gcg and Pyy in the gut, but the extensive distribution of Glp1r and Npy2r in several peripheral tissues suggests that these hormones may have pleiotropic physiological functions in cats.


Assuntos
Gatos/genética , Polipeptídeo Inibidor Gástrico/genética , Peptídeo YY/genética , Proglucagon/genética , Receptores dos Hormônios Gastrointestinais/genética , Receptores de Peptídeos/genética , Animais , Gatos/metabolismo , Polipeptídeo Inibidor Gástrico/metabolismo , Perfilação da Expressão Gênica , Peptídeo YY/metabolismo , Proglucagon/metabolismo , Receptores dos Hormônios Gastrointestinais/metabolismo , Receptores de Peptídeos/metabolismo , Distribuição Tecidual , Transcrição Genética
7.
Obes Facts ; 12(2): 190-198, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30928977

RESUMO

OBJECTIVES: This study was undertaken to compare gut hormone secretion between high-fat-fed and control rats, and to examine the corresponding changes in the expression of sweet taste receptors and glucose transporters in the small intestine and hypothalamus. METHODS: Four-week-old male Sprague Dawley rats were fed a standard or high-fat diet for 8 weeks (10 in each group), followed by an oral glucose tolerance test (50% glucose solution, 2 g/kg). Blood was sampled for glucose, insulin, glucagon-like peptide-1 (GLP-1) and polypeptide YY (PYY) assays. One week later, small intestinal and hypothalamic tissue were analyzed for sweet taste receptor and glucose transporter expression by real-time PCR. RESULTS: After oral glucose, plasma GLP-1 concentrations were higher in high-fat-fed than standard-fat-fed rats (group × time interaction, p < 0.01) with significant differences at t = 15 min (p < 0.01) and 30 min (p < 0.05). Plasma PYY concentrations were lower in high-fat-fed than control rats at t = 0, 15 min (p < 0.05, respectively) and 120 min (p < 0.01). There were no differences in the expression of sweet taste receptors or glucose transporters between high-fat-fed and control rats in the duodenum, ileum, or hypothalamus. CONCLUSIONS: Changes in GLP-1 and PYY secretion after a high-fat diet appear unrelated to any changes in the expression of sweet taste receptors or glucose transporters. Impaired PYY secretion with high-fat feeding suggests that PYY analogues may provide a potential therapy in the treatment of obesity.


Assuntos
Hormônios Gastrointestinais/metabolismo , Proteínas Facilitadoras de Transporte de Glucose/genética , Glucose/metabolismo , Obesidade , Receptores Acoplados a Proteínas-G/genética , Paladar , Animais , Dieta Hiperlipídica , Hormônios Gastrointestinais/genética , Expressão Gênica , Peptídeo 1 Semelhante ao Glucagon/sangue , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Teste de Tolerância a Glucose , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Íleo/metabolismo , Insulina/sangue , Masculino , Obesidade/sangue , Obesidade/genética , Obesidade/metabolismo , Obesidade/patologia , Peptídeo YY/sangue , Peptídeo YY/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores Acoplados a Proteínas-G/metabolismo , Paladar/genética , Percepção Gustatória/genética
8.
Org Biomol Chem ; 17(18): 4543-4553, 2019 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-30994696

RESUMO

We investigate the self-assembly of a palmitoylated (C16-chain at the N terminus) peptide fragment in comparison to the unlipidated peptide EELNRYY, a fragment of the gut hormone peptide PYY3-36. The lipopeptide C16-EELNRYY shows remarkable pH-dependent self-assembly above measured critical aggregation concentrations, forming fibrils at pH 7, but micelles at pH 10. The parent peptide does not show self-assembly behaviour. The lipopeptide forms hydrogels at sufficiently high concentration at pH 7, the dynamic mechanical properties of which were measured. We also show that the tyrosine functionality at the C terminus of EELNRYY can be used to enzymatically produce the pigment melanin. The enzyme tyrosinase oxidises tyrosine into 3,4-dihydroxyphenylalanine (DOPA), DOPA-quinone and further products, eventually forming eumelanin. This is a mechanism of photo-protection in the skin, for this reason controlling tyrosinase activity is a major target for skin care applications and EELNRYY has potential to be developed for such uses.


Assuntos
Lipopeptídeos/química , Melaninas/síntese química , Monofenol Mono-Oxigenase/química , Oligopeptídeos/química , Fragmentos de Peptídeos/química , Peptídeo YY/química , Sequência de Aminoácidos , Corantes Fluorescentes/química , Hidrogéis/química , Concentração de Íons de Hidrogênio , Lipopeptídeos/metabolismo , Micelas , Oligopeptídeos/metabolismo , Fragmentos de Peptídeos/metabolismo , Peptídeo YY/metabolismo , Conformação Proteica em Folha beta , Multimerização Proteica , Pirenos/química , Tirosina/química
9.
Ann Clin Transl Neurol ; 6(3): 486-495, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30911572

RESUMO

Objective: Physiological changes potentially influence disease progression and survival along the Amyotrophic Lateral Sclerosis (ALS)-Frontotemporal dementia (FTD) spectrum. The peripheral peptides that regulate eating and metabolism may provide diagnostic, metabolic, and progression biomarkers. The current study aimed to examine the relationships and biomarker potential of hormonal peptides. Methods: One hundred and twenty-seven participants (36 ALS, 26 ALS- cognitive, patients with additional cognitive behavioral features, and 35 behavioral variant FTD (bvFTD) and 30 controls) underwent fasting blood analyses of leptin, ghrelin, neuropeptide Y (NPY), peptide YY (PYY), and insulin levels. Relationships between endocrine measures, cognition, eating behaviors, and body mass index (BMI) were investigated. Biomarker potential was evaluated using multinomial logistic regression for diagnosis and correlation to disease duration. Results: Compared to controls, ALS and ALS-cognitive had higher NPY levels and bvFTD had lower NPY levels, while leptin levels were increased in all patient groups. All groups had increased insulin levels and a state of insulin resistance compared to controls. Lower NPY levels correlated with increasing eating behavioral change and BMI, while leptin levels correlated with BMI. On multinomial logistic regression, NPY and leptin levels were found to differentiate between diagnosis. Reduced Neuropeptide Y levels correlated with increasing disease duration, suggesting it may be useful as a potential marker of disease progression. Interpretation: ALS-FTD is characterized by changes in NPY and leptin levels that may impact on the underlying regional neurodegeneration as they were predictive of diagnosis and disease duration, offering the potential as biomarkers and for the development of interventional treatments.


Assuntos
Esclerose Amiotrófica Lateral/sangue , Esclerose Amiotrófica Lateral/diagnóstico , Biomarcadores/sangue , Demência Frontotemporal/sangue , Demência Frontotemporal/diagnóstico , Neuropeptídeos/sangue , Biomarcadores/metabolismo , Progressão da Doença , Jejum , Comportamento Alimentar , Feminino , Grelina/sangue , Grelina/metabolismo , Humanos , Insulina/sangue , Insulina/metabolismo , Leptina/sangue , Leptina/metabolismo , Masculino , Pessoa de Meia-Idade , Neuropeptídeo Y/sangue , Neuropeptídeo Y/metabolismo , Neuropeptídeos/metabolismo , Peptídeo YY/sangue , Peptídeo YY/metabolismo , Valor Preditivo dos Testes
10.
Nat Commun ; 10(1): 1029, 2019 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-30833673

RESUMO

Enteroendocrine cells are specialised sensory cells located in the intestinal epithelium and generate signals in response to food ingestion. Whilst traditionally considered hormone-producing cells, there is evidence that they also initiate activity in the afferent vagus nerve and thereby signal directly to the brainstem. We investigate whether enteroendocrine L-cells, well known for their production of the incretin hormone glucagon-like peptide-1 (GLP-1), also release other neuro-transmitters/modulators. We demonstrate regulated ATP release by ATP measurements in cell supernatants and by using sniffer patches that generate electrical currents upon ATP exposure. Employing purinergic receptor antagonists, we demonstrate that evoked ATP release from L-cells triggers electrical responses in neighbouring enterocytes through P2Y2 and nodose ganglion neurones in co-cultures through P2X2/3-receptors. We conclude that L-cells co-secrete ATP together with GLP-1 and PYY, and that ATP acts as an additional signal triggering vagal activation and potentially synergising with the actions of locally elevated peptide hormone concentrations.


Assuntos
Trifosfato de Adenosina/metabolismo , Enterócitos/metabolismo , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Intestinos , Neurônios Aferentes/metabolismo , Vias Aferentes , Animais , Linhagem Celular , Ingestão de Alimentos , Células Enteroendócrinas/metabolismo , Feminino , Cistos Glanglionares/metabolismo , Cistos Glanglionares/patologia , Incretinas/metabolismo , Mucosa Intestinal/inervação , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/patologia , Gânglio Nodoso/metabolismo , Gânglio Nodoso/patologia , Peptídeo YY/metabolismo , Receptores Purinérgicos P2X2/metabolismo , Receptores Purinérgicos P2X3/metabolismo , Nervo Vago/metabolismo
11.
Nutrients ; 11(2)2019 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-30764560

RESUMO

Gut appetite hormone responses may be influenced by meal macronutrients and obesity. The primary aim of this study was to examine in adolescents with obesity and of healthy weight the effect of a high-protein and a high-carbohydrate meal on postprandial gut appetite hormones. A postprandial cross-over study with adolescents 11⁻19 years old was undertaken. Participants consumed, in random order, a high 79% carbohydrate (HCHO) and a high 55% protein (HP) meal. Ghrelin, glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and self-reported appetite were assessed for four hours postprandial. Total energy intake from an ad libitum lunch and remaining 24 h was assessed. Eight adolescents with obesity (OB) and 12 with healthy weight (HW) participated. Compared with HW, OB adolescents displayed a smaller ghrelin iAUC (-25,896.5 ± 7943 pg/mL/4 h vs. -60,863.5 ± 13104 pg/mL/4 h) (p = 0.008) with no effect of meal (p > 0.05). The suppression of ghrelin relative to baseline was similar between OB and HW. Ghrelin suppression was greater following the HP vs. HCHO meal (effect of meal, p = 0.018). Glucose and insulin response were greater following HCHO vs. HP, with responses more marked in OB (time × weight × meal interaction, p = 0.003 and p = 0.018, respectively). There were no effects of weight or macronutrient on GLP-1 or PYY, appetite or subsequent energy intake. The present study demonstrates that dietary protein can modulate postprandial ghrelin responses; however, this did not translate to subsequent changes in subjective appetite or energy intake.


Assuntos
Apetite/efeitos dos fármacos , Carboidratos da Dieta/farmacologia , Proteínas na Dieta/farmacologia , Nutrientes/farmacologia , Obesidade Pediátrica/metabolismo , Adolescente , Apetite/fisiologia , Criança , Estudos Cross-Over , Método Duplo-Cego , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Grelina/genética , Grelina/metabolismo , Peptídeo 1 Semelhante ao Glucagon/genética , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Humanos , Masculino , Peptídeo YY/genética , Peptídeo YY/metabolismo , Adulto Jovem
12.
Cell Rep ; 26(6): 1399-1408.e6, 2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-30726726

RESUMO

Bariatric surgery is widely used to treat obesity and improves type 2 diabetes beyond expectations from the degree of weight loss. Elevated post-prandial concentrations of glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and insulin are widely reported, but the importance of GLP-1 in post-bariatric physiology remains debated. Here, we show that GLP-1 is a major driver of insulin secretion after bariatric surgery, as demonstrated by blocking GLP-1 receptors (GLP1Rs) post-gastrectomy in lean humans using Exendin-9 or in mice using an anti-GLP1R antibody. Transcriptomics and peptidomics analyses revealed that human and mouse enteroendocrine cells were unaltered post-surgery; instead, we found that elevated plasma GLP-1 and PYY correlated with increased nutrient delivery to the distal gut in mice. We conclude that increased GLP-1 secretion after bariatric surgery arises from rapid nutrient delivery to the distal gut and is a key driver of enhanced insulin secretion.


Assuntos
Cirurgia Bariátrica , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Glucose/metabolismo , Homeostase , Obesidade/metabolismo , Adulto , Animais , Células Enteroendócrinas/metabolismo , Feminino , Peptídeo 1 Semelhante ao Glucagon/sangue , Humanos , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Secreção de Insulina , Mucosa Intestinal/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Obesidade/tratamento farmacológico , Obesidade/cirurgia , Fragmentos de Peptídeos/efeitos adversos , Fragmentos de Peptídeos/uso terapêutico , Peptídeo YY/metabolismo , Período Pós-Operatório , Transcriptoma
13.
Am J Physiol Gastrointest Liver Physiol ; 316(5): G574-G584, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30767682

RESUMO

A large number of glucagon-like-peptide-1 (GLP-1)- and peptide-YY (PYY)-producing L cells are located in the colon, but little is known about their contribution to whole body metabolism. Since bile acids (BAs) increase GLP-1 and PYY release, and since BAs spill over from the ileum to the colon, we decided to investigate the ability of BAs to stimulate colonic GLP-1 and PYY secretion. Using isolated perfused rat/mouse colon as well as stimulation of the rat colon in vivo, we demonstrate that BAs significantly enhance secretion of GLP-1 and PYY from the colon with average increases of 3.5- and 2.9-fold, respectively. Furthermore, we find that responses depend on BA absorption followed by basolateral activation of the BA-receptor Takeda-G protein-coupled-receptor 5. Surprisingly, the apical sodium-dependent BA transporter, which serves to absorb conjugated BAs, was not required for colonic conjugated BA absorption or conjugated BA-induced peptide secretion. In conclusion, we demonstrate that BAs represent a major physiological stimulus for colonic L-cell secretion. NEW & NOTEWORTHY By the use of isolated perfused rodent colon preparations we show that bile acids are potent and direct promoters of colonic glucagon-like-peptide 1 and peptide-YY secretion. The study provides convincing evidence that basolateral Takeda-G protein-coupled-receptor 5 activation is mediating the effects of bile acids in the colon and thus add to the existing literature described for L cells in the ileum.


Assuntos
Ácidos e Sais Biliares/metabolismo , Proteínas de Transporte/metabolismo , Colo/metabolismo , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Glicoproteínas de Membrana/metabolismo , Peptídeo YY/metabolismo , Animais , Íleo/metabolismo , Absorção Intestinal/fisiologia , Células L , Camundongos , Ratos
15.
Curr Protein Pept Sci ; 20(7): 750-758, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30678628

RESUMO

Obesity is one of the main challenges of public health in the 21st century. Obesity can induce a series of chronic metabolic diseases, such as diabetes, dyslipidemia, hypertension and nonalcoholic fatty liver, which seriously affect human health. Gut-brain axis, the two-direction pathway formed between enteric nervous system and central nervous system, plays a vital role in the occurrence and development of obesity. Gastrointestinal signals are projected through the gut-brain axis to nervous system, and respond to various gastrointestinal stimulation. The central nervous system regulates visceral activity through the gut-brain axis. Brain-gut peptides have important regulatory roles in the gut-brain axis. The brain-gut peptides of the gastrointestinal system and the nervous system regulate the gastrointestinal movement, feeling, secretion, absorption and other complex functions through endocrine, neurosecretion and paracrine to secrete peptides. Both neuropeptide Y and peptide YY belong to the pancreatic polypeptide family and are important brain-gut peptides. Neuropeptide Y and peptide YY have functions that are closely related to appetite regulation and obesity formation. This review describes the role of the gutbrain axis in regulating appetite and maintaining energy balance, and the functions of brain-gut peptides neuropeptide Y and peptide YY in obesity. The relationship between NPY and PYY and the interaction between the NPY-PYY signaling with the gut microbiota are also described in this review.


Assuntos
Encéfalo/metabolismo , Trato Gastrointestinal/metabolismo , Neuropeptídeo Y/metabolismo , Obesidade/metabolismo , Peptídeo YY/metabolismo , Animais , Homeostase , Humanos , Obesidade/fisiopatologia
16.
EBioMedicine ; 40: 67-76, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30639417

RESUMO

BACKGROUND: Bariatric surgery leads to early and long-lasting remission of type 2 diabetes (T2D). However, the mechanisms behind this phenomenon remain unclear. Among several factors, gut hormones are thought to be crucial mediators of this effect. Unlike GLP-1, the role of the hormone peptide tyrosine tyrosine (PYY) in bariatric surgery in humans has been limited to appetite regulation and its impact on pancreatic islet secretory function and glucose metabolism remains under-studied. METHODS: Changes in PYY concentrations were examined in obese patients after bariatric surgery and compared to healthy controls. Human pancreatic islet function was tested upon treatment with sera from patients before and after the surgery, in presence or absence of PYY. Alterations in intra-islet PYY release and insulin secretion were analysed after stimulation with short chain fatty acids (SCFAs), bile acids and the cytokine IL-22. FINDINGS: We demonstrate that PYY is a key effector of the early recovery of impaired glucose-mediated insulin and glucagon secretion in bariatric surgery. We establish that the short chain fatty acid propionate and bile acids, which are elevated after surgery, can trigger PYY release not only from enteroendocrine cells but also from human pancreatic islets. In addition, we identify IL-22 as a new factor which is modulated by bariatric surgery in humans and which directly regulates PYY expression and release. INTERPRETATION: This study shows that some major metabolic benefits of bariatric surgery can be emulated ex vivo. Our findings are expected to have a direct impact on the development of new non-surgical therapy for T2D correction.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Peptídeo YY/metabolismo , Animais , Cirurgia Bariátrica , Biomarcadores , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/terapia , Células Enteroendócrinas/metabolismo , Feminino , Expressão Gênica , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Humanos , Interleucinas/metabolismo , Ilhotas Pancreáticas/metabolismo , Masculino , Camundongos , Peptídeo YY/sangue , Peptídeo YY/genética , Ratos
17.
Nutrients ; 11(2)2019 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-30678029

RESUMO

INTRODUCTION: Proteins, particularly whey proteins, represent the most satiating macronutrient in animals and humans. A dietetic regimen based on proteins enriched preload before eating might be a strategy to counteract obesity. AIMS AND METHODS: The aim of the present study was to evaluate the effects of an isocaloric drink containing whey proteins or maltodextrins (preload) on appetite (satiety/hunger measured by a visual analogue scale or VAS), glucometabolic control (blood glucose/insulin), and anorexigenic gastrointestinal peptides (pancreatic polypeptide or PP, glucagon-like peptide 1 or GLP-1 and peptide YY or PYY) in a cohort of obese young women (n = 9; age: 18.1 ± 3.0 years; body mass index, BMI: 38.8 ± 4.5 kg/m²). After two and a half hours, they were administered with a mixed meal at a fixed dose; satiety and hunger were measured by VAS. RESULTS: Each drink significantly augmented satiety and reduced hunger, and the effects were more evident with whey proteins than maltodextrins. Similarly, there were significant increases in GLP-1 and PYY levels (but not PP) after the ingestion of each drink; these anorexigenic responses were higher with whey proteins than maltodextrins. While insulinemia identically increased after each drink, whey proteins induced a lower glycemic response than maltodextrins. No differences in satiety and hunger were found after the meal, which is presumably due to the late administration of the meal test, when the hypophagic effect of whey proteins was disappearing. CONCLUSIONS: While whey proteins actually reduce appetite, stimulate anorexigenic gastrointestinal peptides, and improve glucometabolic homeostasis in young obese women, further additional studies are mandatory to demonstrate their hypophagic effects in obese subjects, when administered as preload before eating.


Assuntos
Apetite/efeitos dos fármacos , Glicemia/efeitos dos fármacos , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Obesidade/metabolismo , Polipeptídeo Pancreático/metabolismo , Proteínas do Soro do Leite/farmacologia , Adolescente , Adulto , Glicemia/análise , Feminino , Peptídeo 1 Semelhante ao Glucagon/sangue , Homeostase/efeitos dos fármacos , Humanos , Insulina/sangue , Polipeptídeo Pancreático/sangue , Peptídeo YY/sangue , Peptídeo YY/metabolismo , Polissacarídeos/administração & dosagem , Polissacarídeos/farmacologia , Saciação/efeitos dos fármacos , Proteínas do Soro do Leite/administração & dosagem , Adulto Jovem
18.
J Nutr Biochem ; 64: 80-87, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30471563

RESUMO

Matured hop bitter acids (MHBA) are oxidation products from bitter components in hops, which are used widely as food materials to add flavor and bitterness in beer production. Our previous study has shown that MHBA induces thermogenesis in brown adipose tissue (BAT) via sympathetic nerves in rodents and reduces body fat in healthy adults. However, it is unclear how MHBA affects the sympathetic nervous system. In this study, we demonstrate that MHBA treatment of enteroendocrine cells increases Ca2+ levels and induces the secretion of the gastrointestinal hormone, cholecystokinin (CCK), in a dose-dependent manner. These effects were eliminated by Ca2+ depletion from the medium or blockers of L-type voltage-sensitive Ca2+ channels during pretreatment. Induction of CCK secretion by MHBA was also confirmed using isolated rat small intestines. Elevation of the sympathetic nerve activity innervating BAT (BAT-SNA) and BAT temperature by MHBA administration in rats was blocked by pretreatment with a CCK receptor 1 (CCK1R) antagonist. Moreover, the intraperitoneal injection of CCK fragment elevated BAT-SNA, and this increase was blocked by subdiaphragmatic vagotomy. These results demonstrate that MHBA induces CCK secretion in the gastrointestinal tracts and elevates BAT-SNA via CCK1R and vagal afferent nerves. In addition, MHBA increases BAT temperature via CCK1R. Our findings reveal a novel mechanism of the beneficial metabolic effects of food ingredients.


Assuntos
Tecido Adiposo Marrom/inervação , Colecistocinina/metabolismo , Humulus/química , Intestino Delgado/efeitos dos fármacos , Sistema Nervoso Simpático/efeitos dos fármacos , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Animais , Animais Geneticamente Modificados , Temperatura Corporal/efeitos dos fármacos , Temperatura Corporal/fisiologia , Sinalização do Cálcio/efeitos dos fármacos , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Intestino Delgado/metabolismo , Masculino , Peptídeo YY/metabolismo , Ratos , Ratos Wistar , Sincalida/farmacologia , Nervo Vago/efeitos dos fármacos
19.
Obes Surg ; 29(2): 593-600, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30353248

RESUMO

BACKGROUND: Sleeve gastrectomy with ileal transposition has been shown to be superior to sleeve gastrectomy alone for promoting weight loss in rat and porcine models. The absence of a mouse model for this procedure has impeded efforts to understand the molecular physiology underlying its efficacy. This study demonstrates the long-term survivability of sleeve gastrectomy with ileal transposition in mice. MATERIALS AND METHODS: In this study of technical feasibility, a sleeve gastrectomy with ileal transposition (SGIT), sleeve gastrectomy (SG), or sham surgery (SH) was performed on 7- to 8-week-old C57Bl/6J mice (n = 8 for each). To evaluate long-term survivability, mice were placed on an obesogenic diet and weighed weekly for 10 weeks. The intestinal identity of the transposed segment was assessed with gene expression analysis of duodenal-, jejunal-, and ileal-specific hormones using quantitative polymerase chain reaction. RESULTS: Overall, SGIT better prevented weight gain than the SG or sham procedures (10-week post-operative weight: SH 45.3 ± 1.0 g, SG 41.25 ± 1.6 g, SGIT 35.4 ± 0.8 g). Gene expression pattern analysis of three markers of intestinal identity (gastrin, cholecystokinin, and peptide YY) suggests that the ileal identity of the transposed segment is maintained 10 weeks after transposition. CONCLUSIONS: We demonstrate for the first time a reproducible mouse model of sleeve gastrectomy with ileal transposition. Future studies utilizing this model will expand our understanding of the molecular pathways through which the hindgut regulates satiety.


Assuntos
Gastrectomia/métodos , Íleo/cirurgia , Animais , Biomarcadores , Glicemia/análise , Colecistocinina/genética , Colecistocinina/metabolismo , Modelos Animais de Doenças , Estudos de Viabilidade , Gastrinas/genética , Gastrinas/metabolismo , Expressão Gênica , Camundongos Endogâmicos C57BL , Peptídeo YY/genética , Peptídeo YY/metabolismo , RNA/metabolismo , Distribuição Aleatória , Perda de Peso
20.
Appetite ; 132: 18-24, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30266581

RESUMO

In young individuals, oral free fatty acid delays gastric emptying, promotes gut hormone release, and reduces energy intake more than an isocaloric load of triglyceride does. The objective of this study was to compare the effects of the free fatty acid oleic acid (OA) and the triglyceride olive oil (OO) on gastrointestinal motility, gut hormone secretion, and energy intake in older and middle-aged healthy volunteers. In a double-blind, randomized, cross-over, study 10 older (age 83.0 ±â€¯3.4 (mean ±â€¯SD) years) and 10 middle-aged (age 43.1 ±â€¯8.9 years) men were examined on two occasions to evaluate the effect of isocaloric and isovolaemic loads of radiolabelled OA or OO on gastric emptying, oro-caecal transit, glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) secretions, and energy intake. Gastric emptying was slower in older than in middle-aged men (lipid p < 0.001, water p = 0.010), while no difference between these groups was found for oro-caecal transit. In comparison with OO, OA caused slower gastric emptying (lipid p < 0.001, water p = 0.020) and faster oro-caecal transit (p = 0.025). Postprandial secretion of GLP-1 and PYY was comparable for older and middle-aged men, as well as for OA and OO. Older men ingested less energy than middle-aged men did (p < 0.001) and their energy intake was lower after OA than OO (p = 0.002). Thus, gastric emptying of an oral lipid load is slower in older than in middle-aged men; gastric emptying is slower and oro-caecal transit faster after OA than OO in both age groups; and older men ingest less energy than middle-aged men and less energy after OA than OO.


Assuntos
Ingestão de Energia , Ácidos Graxos não Esterificados/administração & dosagem , Hormônios Gastrointestinais/metabolismo , Motilidade Gastrointestinal , Triglicerídeos/administração & dosagem , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Esvaziamento Gástrico , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Ácido Oleico/administração & dosagem , Azeite de Oliva/administração & dosagem , Peptídeo YY/metabolismo
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