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Sung H, Heaton E, Dus M. Taste Plasticity in Nutrition and Health: A Scoping Review. Nutrients 2025; 17:1336. [PMID: 40284201 PMCID: PMC12030297 DOI: 10.3390/nu17081336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2025] [Revised: 03/31/2025] [Accepted: 04/10/2025] [Indexed: 04/29/2025] Open
Abstract
Taste sensation is at the intersection of nutrition and health. Our food choices are shaped by the foods we like, but our dietary habits can, in turn, influence how we sense food. This phenomenon, known as diet-induced taste plasticity, has received renewed attention as a tool for designing healthier foods and retraining eating habits. This review synthesizes emerging data from humans and model organisms to characterize how dietary environments shape taste sensation while exploring its underlying molecular and physiological mechanisms. Although there is still so much to discover about this phenomenon, accumulating evidence suggests an inverse relationship between a tastant concentration and the ability of the organism to respond to it. The effects largely depend on diet, but body weight changes play a role in specific dietary settings. Several mechanisms are at play, including receptor abundance and function, neuroendocrine signaling, gene expression, and neuroinflammation. Many open questions on mechanisms remain, including the concentration and times of exposure for effects to manifest and the consequences for nutrition and health. Beyond mechanisms, future research should explore strategies to leverage taste adaptation for healthier food design.
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Affiliation(s)
| | | | - Monica Dus
- Department of Molecular, Cellular, and Developmental Biology, The University of Michigan College of Literature, Science, and the Arts, Ann Arbor, MI 48103, USA; (H.S.); (E.H.)
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2
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Keel PK, Bodell LP, Ali SI, Starkey A, Trotta J, Luxama JW, Halfhide C, Hill NG, Appelbaum J, Williams DL. Examining Weight Suppression, Leptin Levels, Glucagon-Like Peptide 1 Response, and Reward-Related Constructs in Severity and Maintenance of Bulimic Syndromes: Protocol and Sample Characteristics for a Cross-Sectional and Longitudinal Study. JMIR Res Protoc 2025; 14:e66554. [PMID: 40198107 PMCID: PMC12015349 DOI: 10.2196/66554] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Revised: 12/20/2024] [Accepted: 03/05/2025] [Indexed: 04/10/2025] Open
Abstract
BACKGROUND Bulimia nervosa and related syndromes (BN-S) characterized by binge eating vary considerably in illness severity and course. Using the Research Domain Criteria framework of the National Institute of Mental Health, we developed a model positing that the same set of physiological consequences of weight suppression (WS; defined as the difference between the highest and current adult body weight) contribute to binge-eating severity and maintenance by (1) increasing the drive or motivation to consume food (reward valuation effort [RVE]) and (2) decreasing the ability for food consumption to lead to a state of satiation or satisfaction (reward satiation). OBJECTIVE Our funded project aimed to test concurrent associations among WS, physiological factors (leptin concentrations and postprandial glucagon-like peptide 1 [GLP-1] response), behavioral indicators of RVE (breakpoint on progressive ratio tasks) and reward satiation (ad-lib test meal intake), self-report of these core constructs, and binge-eating severity in BN-S (aim 1); test prospective associations to determine whether WS predicts BN-S maintenance in longitudinal models and whether posited mediators also predict BN-S maintenance (aim 2); and determine whether associations between WS and BN-S severity and maintenance are mediated by alterations in leptin levels, GLP-1 response, RVE, and reward satiation (aim 3). METHODS We aimed to recruit a sample of 320 women with BN-S or noneating disorder controls, with BMI from 16 kg/m2 to 35 kg/m2, for our study. The study included diagnostic interviews; questionnaires; height, weight, and percentage of body fat measurements; weight history; fasting leptin level; postprandial GLP-1 and insulin responses to a fixed meal; and ad-lib meal and progressive ratio tasks to behaviorally measure reward satiation and RVE, respectively, at baseline, with at least 78.1% (250/320) of the participants providing data at 6- and 12-month follow-up visits. Data will be analyzed using structural equation models to test posited pathways. RESULTS Data collection began in November 2016 and ended in April 2023, pausing in-person data collection from March 2020 to February 2021 due to the COVID-19 pandemic. Of 399 eligible women enrolled, 290 (72.7%) provided clinical, behavioral, and biological data at baseline, and 249 (62.4%) provided follow-up data. Measures demonstrated strong psychometric properties. CONCLUSIONS We seek to identify biobehavioral predictors to inform treatments that target key factors influencing the severity and course of binge eating. These data, supported solely through federal funding, can inform questions emerging from recent interest and controversy surrounding the use of GLP-1 agonists for binge eating. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) RR1-10.2196/66554.
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Affiliation(s)
- Pamela K Keel
- Department of Psychology, Florida State University, Tallahassee, FL, United States
| | - Lindsay P Bodell
- Department of Psychology, Western University, London, ON, Canada
| | - Sarrah I Ali
- Department of Psychology, Florida State University, Tallahassee, FL, United States
| | - Austin Starkey
- Department of Psychology, Louisiana State University, Baton Rouge, LA, United States
| | - Jenna Trotta
- Department of Psychology, Florida State University, Tallahassee, FL, United States
| | - J Woody Luxama
- College of Medicine, University of Central Florida, Orlando, FL, United States
| | | | - Naomi G Hill
- Department of Psychology, Ohio University, Athens, OH, United States
| | - Jonathan Appelbaum
- College of Medicine, Florida State University, Tallahassee, FL, United States
| | - Diana L Williams
- Kravis Department of Integrated Sciences, Claremont McKenna College, Claremont, CA, United States
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Alagha M, Al-Alam F, Saroufine K, Elias L, Klaimi M, Nabbout G, Harb F, Azar S, Nahas N, Ghadieh HE. Binge Eating Disorder and Metabolic Syndrome: Shared Mechanisms and Clinical Implications. Healthcare (Basel) 2025; 13:482. [PMID: 40077044 PMCID: PMC11898466 DOI: 10.3390/healthcare13050482] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2025] [Revised: 02/14/2025] [Accepted: 02/21/2025] [Indexed: 03/14/2025] Open
Abstract
Background: Binge eating disorder (BED) is characterized by episodes of uncontrollable eating, defined by the rapid consumption of large quantities of food over a short period. This condition is associated with a variety of psychological and non-psychological factors, including behavioral, biological, genetic, neurological, and pharmacological influences, all of which adversely affect patients' daily lives. BED is linked to numerous health consequences, such as obesity, atherosclerosis, diabetes, chronic pain, and hypertension. Although BED is not exclusive to individuals with obesity, it is more prevalent in this population, who also face a heightened risk of developing metabolic syndrome (MetS). The latter is a cluster of five risk factors-obesity, hyperlipidemia, hyperinsulinemia, hypertension, and hyperglycemia-that significantly increase the likelihood of chronic diseases. Methods: This narrative review synthesizes existing research to explore the association between BED and MetS, examining shared pathophysiological mechanisms and clinical implications. It also highlights the role of escalating food insecurity and ongoing political, economic, and health crises in the development of BED. Results: BED is significantly associated with MetS components, including hypertension, obesity, type 2 diabetes, and dyslipidemia, all contributing to increased morbidity and mortality. Beyond body weight, behavioral, genetic, biological, and neurological factors mediate this relationship. Conclusions: BED is strongly linked to MetS through shared behavioral, genetic, and biological pathways. Early detection, integrated management strategies, and further research are crucial to addressing the public health challenges posed by this association.
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Affiliation(s)
- Michel Alagha
- Department of Biomedical Sciences, Faculty of Medicine and Medical Sciences, University of Balamand, Al-Koura, Tripoli P.O. Box 100, Lebanon; (M.A.); (K.S.); (L.E.); (G.N.); (F.H.); (S.A.)
| | - Firas Al-Alam
- Department of Psychology, Faculty of Arts and Sciences, University of Balamand, Al-Koura, Tripoli P.O. Box 100, Lebanon; (F.A.-A.); (N.N.)
| | - Karmen Saroufine
- Department of Biomedical Sciences, Faculty of Medicine and Medical Sciences, University of Balamand, Al-Koura, Tripoli P.O. Box 100, Lebanon; (M.A.); (K.S.); (L.E.); (G.N.); (F.H.); (S.A.)
| | - Linda Elias
- Department of Biomedical Sciences, Faculty of Medicine and Medical Sciences, University of Balamand, Al-Koura, Tripoli P.O. Box 100, Lebanon; (M.A.); (K.S.); (L.E.); (G.N.); (F.H.); (S.A.)
| | - Mark Klaimi
- Department of Biology, Faculty of Arts and Sciences, University of Balamand, Al-Koura, Tripoli P.O. Box 100, Lebanon;
| | - Ghassan Nabbout
- Department of Biomedical Sciences, Faculty of Medicine and Medical Sciences, University of Balamand, Al-Koura, Tripoli P.O. Box 100, Lebanon; (M.A.); (K.S.); (L.E.); (G.N.); (F.H.); (S.A.)
| | - Frederic Harb
- Department of Biomedical Sciences, Faculty of Medicine and Medical Sciences, University of Balamand, Al-Koura, Tripoli P.O. Box 100, Lebanon; (M.A.); (K.S.); (L.E.); (G.N.); (F.H.); (S.A.)
| | - Sami Azar
- Department of Biomedical Sciences, Faculty of Medicine and Medical Sciences, University of Balamand, Al-Koura, Tripoli P.O. Box 100, Lebanon; (M.A.); (K.S.); (L.E.); (G.N.); (F.H.); (S.A.)
| | - Nayla Nahas
- Department of Psychology, Faculty of Arts and Sciences, University of Balamand, Al-Koura, Tripoli P.O. Box 100, Lebanon; (F.A.-A.); (N.N.)
| | - Hilda E. Ghadieh
- Department of Biomedical Sciences, Faculty of Medicine and Medical Sciences, University of Balamand, Al-Koura, Tripoli P.O. Box 100, Lebanon; (M.A.); (K.S.); (L.E.); (G.N.); (F.H.); (S.A.)
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Wei J, Wu H, Zheng Y, Wang N, Benedict C, Chen W, Tan X. Adequate sleep duration accentuates the effect of glucagon-like peptide-1 receptor variant on HbA1c: A gene-environment interaction study. Diabetes Res Clin Pract 2024; 218:111927. [PMID: 39536975 DOI: 10.1016/j.diabres.2024.111927] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Revised: 10/24/2024] [Accepted: 11/10/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND Both glucagon-like peptide-1 receptor (GLP1R) agonists and lifestyle modifications are widely adopted in managing glycemia. However, the joint effects of GLP1R agonists with lifestyle on glycemic traits have not been evaluated. METHODS This gene-environment study tested the interaction between GLP1R-rs10305492 variant, consistent with the effect of GLP1R agonist therapies, and four lifestyle factors (diet, physical activity, sleep duration, and chronotype) for glucose and glycated hemoglobin (HbA1c) levels among 263,846 UK Biobank participants. Linear regression models were conducted to evaluate the effects of the rs10305492 and lifestyle factors on glucose and HbA1c levels. RESULTS GLP1R-rs10305492-AA/AG genotype combined a healthy diet, regular physical activity, adequate sleep duration, or morning chronotype were associated with lower glucose and HbA1c levels (all P for trend < 0.001). A synergistic effect was found between rs10305492 and sleep duration on HbA1c, suggesting a recommended adequate sleep duration (7-8 h/day) may amplify the HbA1c lowering effect of GLP1R agonists. Joint effects of the rs10305492 and adequate sleep were associated with a 26 % reduced risk of hyperglycemia (>7.8 mmol/L) risk and a 22 % lower of high HbA1c (>39 mmol/mol or 5.7 %). CONCLUSIONS Combining GLP1R agonists with adequate sleep may provide additional benefits for glycemic control in clinical practice.
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Affiliation(s)
- Jiahe Wei
- Department of Big Data in Health Science, Zhejiang University School of Public Health and Department of Psychiatry, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China; The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Hangzhou, China
| | - Hanzhang Wu
- Department of Big Data in Health Science, Zhejiang University School of Public Health and Department of Psychiatry, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China; The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Hangzhou, China
| | - Ying Zheng
- Department of Big Data in Health Science, Zhejiang University School of Public Health and Department of Psychiatry, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China; The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Hangzhou, China
| | - Ningjian Wang
- Department of Endocrinology and Metabolism, Institute of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Christian Benedict
- Molecular Neuropharmacology, Department of Pharmaceutical Biosciences, Uppsala University, 75124, Uppsala, Sweden
| | - Wei Chen
- Department of Psychiatry, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
| | - Xiao Tan
- Department of Big Data in Health Science, Zhejiang University School of Public Health and Department of Psychiatry, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China; The Key Laboratory of Intelligent Preventive Medicine of Zhejiang Province, Hangzhou, China; Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
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Habib S. Team players in the pathogenesis of metabolic dysfunctions-associated steatotic liver disease: The basis of development of pharmacotherapy. World J Gastrointest Pathophysiol 2024; 15:93606. [PMID: 39220834 PMCID: PMC11362842 DOI: 10.4291/wjgp.v15.i4.93606] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Revised: 05/14/2024] [Accepted: 07/23/2024] [Indexed: 08/22/2024] Open
Abstract
Nutrient metabolism is regulated by several factors. Social determinants of health with or without genetics are the primary regulator of metabolism, and an unhealthy lifestyle affects all modulators and mediators, leading to the adaptation and finally to the exhaustion of cellular functions. Hepatic steatosis is defined by presence of fat in more than 5% of hepatocytes. In hepatocytes, fat is stored as triglycerides in lipid droplet. Hepatic steatosis results from a combination of multiple intracellular processes. In a healthy individual nutrient metabolism is regulated at several steps. It ranges from the selection of nutrients in a grocery store to the last step of consumption of ATP as an energy or as a building block of a cell as structural component. Several hormones, peptides, and genes have been described that participate in nutrient metabolism. Several enzymes participate in each nutrient metabolism as described above from ingestion to generation of ATP. As of now several publications have revealed very intricate regulation of nutrient metabolism, where most of the regulatory factors are tied to each other bidirectionally, making it difficult to comprehend chronological sequence of events. Insulin hormone is the primary regulator of all nutrients' metabolism both in prandial and fasting states. Insulin exerts its effects directly and indirectly on enzymes involved in the three main cellular function processes; metabolic, inflammation and repair, and cell growth and regeneration. Final regulators that control the enzymatic functions through stimulation or suppression of a cell are nuclear receptors in especially farnesoid X receptor and peroxisome proliferator-activated receptor/RXR ligands, adiponectin, leptin, and adiponutrin. Insulin hormone has direct effect on these final modulators. Whereas blood glucose level, serum lipids, incretin hormones, bile acids in conjunction with microbiota are intermediary modulators which are controlled by lifestyle. The purpose of this review is to overview the key players in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) that help us understand the disease natural course, risk stratification, role of lifestyle and pharmacotherapy in each individual patient with MASLD to achieve personalized care and target the practice of precision medicine. PubMed and Google Scholar databases were used to identify publication related to metabolism of carbohydrate and fat in states of health and disease states; MASLD, cardiovascular disease and cancer. More than 1000 publications including original research and review papers were reviewed.
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Affiliation(s)
- Shahid Habib
- Department of Hepatology, Liver Institute PLLC, Tucson, AZ 85712, United States
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Perez-Leighton C, Kerr B, Scherer PE, Baudrand R, Cortés V. The interplay between leptin, glucocorticoids, and GLP1 regulates food intake and feeding behaviour. Biol Rev Camb Philos Soc 2024; 99:653-674. [PMID: 38072002 DOI: 10.1111/brv.13039] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 11/21/2023] [Accepted: 12/01/2023] [Indexed: 05/09/2024]
Abstract
Nutritional, endocrine, and neurological signals converge in multiple brain centres to control feeding behaviour and food intake as part of the allostatic regulation of energy balance. Among the several neuroendocrine systems involved, the leptin, glucocorticoid, and glucagon-like peptide 1 (GLP1) systems have been extensively researched. Leptin is at the top hierarchical level since its complete absence is sufficient to trigger severe hyperphagia. Glucocorticoids are key regulators of the energy balance adaptation to stress and their sustained excess leads to excessive adiposity and metabolic perturbations. GLP1 participates in metabolic adaptation to food intake, regulating insulin secretion and satiety by parallel central and peripheral signalling systems. Herein, we review the brain and peripheral targets of these three hormone systems that integrate to regulate food intake, feeding behaviour, and metabolic homeostasis. We examine the functional relationships between leptin, glucocorticoids, and GLP1 at the central and peripheral levels, including the cross-regulation of their circulating levels and their cooperative or antagonistic actions at different brain centres. The pathophysiological roles of these neuroendocrine systems in dysregulated intake are explored in the two extremes of body adiposity - obesity and lipodystrophy - and eating behaviour disorders.
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Affiliation(s)
- Claudio Perez-Leighton
- Departmento de Fisiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Av. Libertador Bernardo O'Higgins 340, Santiago, 830024, Chile
| | - Bredford Kerr
- Centro de Biología Celular y Biomedicina-CEBICEM, Facultad de Medicina y Ciencia, Universidad San Sebastián, Carmen Sylva 2444, Providencia, Santiago, Chile
| | - Philipp E Scherer
- Touchstone Diabetes Center, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390, USA
| | - René Baudrand
- Departmento de Endocrinología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Av. Libertador Bernardo O'Higgins 340, Santiago, 830024, Chile
- Centro Translacional de Endocrinología (CETREN), Facultad de Medicina, Pontificia Universidad Católica de Chile, Av. Libertador Bernardo O'Higgins 340, Santiago, 830024, Chile
| | - Víctor Cortés
- Departmento de Nutrición, Diabetes y Metabolismo, Facultad de Medicina, Pontificia Universidad Católica de Chile, Av. Libertador Bernardo O'Higgins 340, Santiago, 830024, Chile
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Paiva IHRD, Maciel LM, Silva RSD, Mendonça IP, Souza JRBD, Peixoto CA. Prebiotics modulate the microbiota-gut-brain axis and ameliorate anxiety and depression-like behavior in HFD-fed mice. Food Res Int 2024; 182:114153. [PMID: 38519181 DOI: 10.1016/j.foodres.2024.114153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Revised: 02/05/2024] [Accepted: 02/17/2024] [Indexed: 03/24/2024]
Abstract
Previous research has demonstrated that Prebiotics can influence the composition of the gut microbiota, consequently impacting mood regulation. This study aimed to assess the effects of Prebiotics, specifically Fructooligosaccharides (FOS) and Galactooligosaccharides (GOS) on neuroinflammation, depression, and anxiety-like behavior in a mouse model fed a high-fat diet (HFD). Initially, mice were divided into two groups: a control group on a standard diet (n = 15) and a group on an HFD for 18 weeks (n = 45). By the 13th week, the HFD group was further divided into experimental groups: Control (n = 15), HFD (n = 15), HFD receiving Prebiotics (n = 15), and HFD receiving Fluoxetine (n = 15). From the 13th week onward, the HFD + Prebiotics group received both the high-fat diet and a combination of FOS and GOS, while the HFD + Fluoxetine group received Fluoxetine in their drinking water. In the 18th week, all mice underwent tests to evaluate behavior, including the Tail Suspension Test (TST), Forced Swimming Test (FST), Sucrose Preference Test (SPT), and the Plus Maze Test (PMT), after which they were euthanized. Mice on the HFD exhibited increased body weight, abdominal size, blood glucose, triglyceride levels, cholesterol, insulin, HOMA index, and higher serum IL-1β. These obese mice also displayed an increased number of microglia and astrocytes, activation of the TLR4 pathway, and elevated levels of neuroinflammatory markers like TNF-α, IL-1β, and COX-2. Moreover, obese mice showed increased activation of the IDO pathway and decreased levels of NMDA receptors. Additionally, markers of neurogenesis and synaptic plasticity, such as PSD, SAP 102, CREB-p, and BDNF, were lower. Treatment with FOS and GOS reversed symptoms of depression and anxiety in mice subjected to HD. This improvement in behavior resulted from a reduction in dysbiosis with an increase in acetate-producing bacteria (B. acidifaciens and B. dorei) and intestinal permeability, leading to a decrease in chronic peripheral and central inflammation. Furthermore, the modulation of the gut-brain axis by FOS and GOS promoted elevated acetate and GPR43 levels in the brain and a reduction in the levels of pro-inflammatory cytokines, positively impacting signaling pathways of neuronal proliferation and survival in the hippocampus and prefrontal cortex.
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Affiliation(s)
- Igor Henrique Rodrigues de Paiva
- Laboratory of Ultrastructure, Aggeu Magalhães Institute (IAM), PE, Brazil; Postgraduate Program in Biological Sciences/Center of Biosciences, Federal University of Pernambuco (UFPE), Recife, PE, Brazil.
| | - Laís Macedo Maciel
- Laboratory of Ultrastructure, Aggeu Magalhães Institute (IAM), PE, Brazil
| | - Rodrigo Soares da Silva
- Laboratory of Ultrastructure, Aggeu Magalhães Institute (IAM), PE, Brazil; Postgraduate Program in Biological Sciences/Center of Biosciences, Federal University of Pernambuco (UFPE), Recife, PE, Brazil
| | - Ingrid Prata Mendonça
- Laboratory of Ultrastructure, Aggeu Magalhães Institute (IAM), PE, Brazil; Postgraduate Program in Biological Sciences/Center of Biosciences, Federal University of Pernambuco (UFPE), Recife, PE, Brazil
| | | | - Christina Alves Peixoto
- Laboratory of Ultrastructure, Aggeu Magalhães Institute (IAM), PE, Brazil; Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM), Brazil.
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Sangsuriyothai P, Watari I, Serirukchutarungsee S, Satrawaha S, Podyma-Inoue KA, Ono T. Expression of glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in the rat submandibular gland is influenced by pre- and post-natal high-fat diet exposure. Front Physiol 2024; 15:1357730. [PMID: 38595641 PMCID: PMC11002158 DOI: 10.3389/fphys.2024.1357730] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Accepted: 02/20/2024] [Indexed: 04/11/2024] Open
Abstract
Background: Incretins, i.e., glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) promote insulin secretion to reduce postprandial blood sugar. Previous studies found incretins in the salivary glands. However, the role of GLP-1 and GIP in the submandibular gland (SMG) is unclear. This study investigates the effects of a high-fat diet (HFD) on the expression of GLP-1 and GIP throughout the development of rat SMG. Methods: Pregnant 11-week-old Wistar rats were divided into two groups: those fed on a standard diet (n = 5) and those fed on a HFD (n = 5). From day 7 of pregnancy and throughout the lactation period, all the rats were fed on either a chow diet or HFD. The newborns were divided into four subgroups (n = 6): standard diet males (SM), HFD males (HM), standard diet females (SF), and HFD females (HF). The SMGs of 3- and 10-week-old rats from each subgroup were collected under general anesthesia. Moreover, body weight, food intake, and fasting blood sugar were measured. The mRNA expression of GLP-1 and GIP was quantified, and the localization was observed using immunohistochemistry (p < 0.05). Results: GLP-1 mRNA expression was statistically significantly more upregulated in HM than in HF at 3 weeks. Moreover, GLP-1 mRNA expression was significantly higher in HM than in both SM and HF at 10 weeks. Although a decreasing trend was observed in GIP mRNA expression in both 3- and 10-week-old rats fed on a HFD, a significant difference between HM and SM only occurred at 3 weeks. Furthermore, the GIP mRNA expression of HM was lower than that of HF at 10 weeks. Immunohistochemical staining revealed GLP-1 and GIP expression mainly in the SMG duct system. Moreover, vacuolated cytoplasm in the duct was observed in rats fed on a HFD. Conclusion: Exposure to HFD during pre- and post-natal periods increased GLP-1 mRNA expression in the SMGs of male rats. However, GIP expression decreased following the HFD in male newborns. Furthermore, a decreasing trend of GIP mRNA expression was observed in male newborns after HFD feeding. Sex influenced incretin hormones secretion and obesity-related conditions. HFD during pre- and post-natal periods reprograms the epigenome, contributing to subsequent disease development.
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Affiliation(s)
- Pornchanok Sangsuriyothai
- Department of Orthodontic Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan
- Department of Orthodontics, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
| | - Ippei Watari
- Department of Orthodontic Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan
| | - Saranya Serirukchutarungsee
- Department of Orthodontic Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan
- Department of Pedodontics and Preventive Dentistry, Faculty of Dentistry, Srinakharinwirot University, Bangkok, Thailand
| | - Sirichom Satrawaha
- Department of Orthodontics, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
| | - Katarzyna Anna Podyma-Inoue
- Department of Biochemistry, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan
| | - Takashi Ono
- Department of Orthodontic Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan
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Yin M, Wang Y, Han M, Liang R, Li S, Wang G, Gang X. Mechanisms of bariatric surgery for weight loss and diabetes remission. J Diabetes 2023; 15:736-752. [PMID: 37442561 PMCID: PMC10509523 DOI: 10.1111/1753-0407.13443] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 06/12/2023] [Accepted: 06/26/2023] [Indexed: 07/15/2023] Open
Abstract
Obesity and type 2 diabetes(T2D) lead to defects in intestinal hormones secretion, abnormalities in the composition of bile acids (BAs), increased systemic and adipose tissue inflammation, defects of branched-chain amino acids (BCAAs) catabolism, and dysbiosis of gut microbiota. Bariatric surgery (BS) has been shown to be highly effective in the treatment of obesity and T2D, which allows us to view BS not simply as weight-loss surgery but as a means of alleviating obesity and its comorbidities, especially T2D. In recent years, accumulating studies have focused on the mechanisms of BS to find out which metabolic parameters are affected by BS through which pathways, such as which hormones and inflammatory processes are altered. The literatures are saturated with the role of intestinal hormones and the gut-brain axis formed by their interaction with neural networks in the remission of obesity and T2D following BS. In addition, BAs, gut microbiota and other factors are also involved in these benefits after BS. The interaction of these factors makes the mechanisms of metabolic improvement induced by BS more complicated. To date, we do not fully understand the exact mechanisms of the metabolic alterations induced by BS and its impact on the disease process of T2D itself. This review summarizes the changes of intestinal hormones, BAs, BCAAs, gut microbiota, signaling proteins, growth differentiation factor 15, exosomes, adipose tissue, brain function, and food preferences after BS, so as to fully understand the actual working mechanisms of BS and provide nonsurgical therapeutic strategies for obesity and T2D.
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Affiliation(s)
- Mengsha Yin
- Department of Endocrinology and MetabolismThe First Hospital of Jilin UniversityChangchunChina
| | - Yao Wang
- Department of OrthopedicsThe Second Hospital Jilin UniversityChangchunChina
| | - Mingyue Han
- Department of Endocrinology and MetabolismThe First Hospital of Jilin UniversityChangchunChina
| | - Ruishuang Liang
- Department of Endocrinology and MetabolismThe First Hospital of Jilin UniversityChangchunChina
| | - Shanshan Li
- Department of Endocrinology and MetabolismThe First Hospital of Jilin UniversityChangchunChina
| | - Guixia Wang
- Department of Endocrinology and MetabolismThe First Hospital of Jilin UniversityChangchunChina
| | - Xiaokun Gang
- Department of Endocrinology and MetabolismThe First Hospital of Jilin UniversityChangchunChina
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10
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Zečević K, Popović N, Vuksanović Božarić A, Vukmirović M, Rizzo M, Muzurović E. Timing Is Important-Management of Metabolic Syndrome According to the Circadian Rhythm. Biomedicines 2023; 11:biomedicines11041171. [PMID: 37189789 DOI: 10.3390/biomedicines11041171] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2023] [Revised: 04/01/2023] [Accepted: 04/10/2023] [Indexed: 05/17/2023] Open
Abstract
Physiological processes occur in accordance with a rhythm regulated by the endogenous biological clock. This clock is programmed at the molecular level and synchronized with the daily light-dark cycle, as well as activities such as feeding, exercise, and social interactions. It consists of the core clock genes, Circadian Locomotor Output Cycles Protein Kaput (CLOCK) and Brain and Muscle Arnt-Like protein 1 (BMAL1), and their products, the period (PER) and cryptochrome (CRY) proteins, as well as an interlocked feedback loop which includes reverse-strand avian erythroblastic leukemia (ERBA) oncogene receptors (REV-ERBs) and retinoic acid-related orphan receptors (RORs). These genes are involved in the regulation of metabolic pathways and hormone release. Therefore, circadian rhythm disruption leads to development of metabolic syndrome (MetS). MetS refers to a cluster of risk factors (RFs), which are not only associated with the development of cardiovascular (CV) disease (CVD), but also with increased all-cause mortality. In this review, we consider the importance of the circadian rhythm in the regulation of metabolic processes, the significance of circadian misalignment in the pathogenesis of MetS, and the management of MetS in relation to the cellular molecular clock.
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Affiliation(s)
- Ksenija Zečević
- Faculty of Medicine, University of Montenegro, 81000 Podgorica, Montenegro
| | - Nataša Popović
- Faculty of Medicine, University of Montenegro, 81000 Podgorica, Montenegro
| | | | - Mihailo Vukmirović
- Faculty of Medicine, University of Montenegro, 81000 Podgorica, Montenegro
- Cardiology Clinic, Clinical Center of Montenegro, 81000 Podgorica, Montenegro
| | - Manfredi Rizzo
- Promise Department, School of Medicine, University of Palermo, 90127 Palermo, Italy
| | - Emir Muzurović
- Faculty of Medicine, University of Montenegro, 81000 Podgorica, Montenegro
- Department of Internal Medicine, Endocrinology Section, Clinical Center of Montenegro, 81000 Podgorica, Montenegro
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11
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Effects of Lactobacillus acidophilus administration to anorexigenic neuropeptides and some biochemical parameters on rats fed with a high-fat diet. Prostaglandins Other Lipid Mediat 2023; 166:106729. [PMID: 36914021 DOI: 10.1016/j.prostaglandins.2023.106729] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Revised: 03/07/2023] [Accepted: 03/09/2023] [Indexed: 03/15/2023]
Abstract
AIM One of the rapidly rising global public health concern is obesity. Over the past three decades, the prevalence of obesity has doubled/tripled in several nations around the world, most likely as a result of urbanization, sedentary lifestyles, and increased intake of high-calorie processed foods. In this study, it was aimed to investigate the effects of Lactobacillus acidophilus administration on rats exposed to high-fat diet experimentally on anorexigenic peptides in the brain and some biochemical parameters in the serum. METHODS In the study, 4 different experimental groups were formed. Group 1 was designated as the control group and fed with a standard rat chow (SD). Group 2 was designated as the high-fat diet (HFD) fed group. Group 3 fed with SD and L. acidophilus probiotic administered. Group 4 fed with HFD and L. acidophilus probiotic administered. At the end of the experiment, leptin, serotonin, glucagon-like peptide-1 (GLP-1) levels were measured in the brain tissue and serum. Glucose, total cholesterol (TC), triglyceride (TG), total protein (TP), albumin, uric acid, aspartate transaminase (AST), alanine aminotransferase (ALT) levels were determined in the serum. RESULTS At the end of the study, it was found that there was an increase in body weight and body mass index in Group 2 compared to Group 1. It was determined that the levels of AST, ALT, TG, TC, glucose, leptin in the serum were significantly high (P < 0.05). The levels of GLP-1 and serotonin in the serum and in the brain were significantly low (P < 0.05). There was a significant decrease in TG and TC in Groups 3 and 4 compared to Group 2 (P < 0.05). The leptin hormone levels in serum and brain were significantly higher in Group 2 than in other groups (P < 0.05). GLP-1 and serotonin levels were found to be significantly low (P < 0.05). The leptin levels in the serum of Groups 3 and 4 decreased significantly compared to Group 2 (P < 0.05). CONCLUSION It was found that probiotic supplementation in high-fat diet had positive effects on anorexigenic peptides. It was concluded that L. acidophilus probiotic can be recommended as a food supplement in the treatment of obesity.
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Bodilly L, Williamson L, Howell K, Alder MN, Kaplan JM. OBESE MICE WITH PNEUMONIA HAVE HYPERLEPTINEMIA AND INCREASED PULMONARY SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION 3 ACTIVATION. Shock 2023; 59:409-416. [PMID: 36597767 PMCID: PMC9991986 DOI: 10.1097/shk.0000000000002050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
ABSTRACT Obesity is an ongoing epidemic that influences pathobiology in numerous disease states. Obesity is associated with increased plasma leptin levels, a hormone that activates the signal transducer and activator of transcription 3 (STAT3) pathway. Pneumonia is a significant cause of morbidity and mortality. During pneumonia, inflammatory pathways including STAT3 are activated. Outcomes in obese patients with pneumonia are mixed, with some studies showing obesity increases harm and others showing benefit. It is unclear whether obesity alters STAT3 activation during bacterial pneumonia and how this might impact outcomes from pneumonia. We used a murine model of obesity and pneumonia challenge with Pseudomonas aeruginosa in obese and nonobese mice to investigate the effect of obesity on STAT3 activation. We found obese mice with bacterial pneumonia had increased mortality compared with nonobese mice. Inflammatory markers, IL-6 and TNF-α, and lung neutrophil infiltration were elevated at 6 h after pneumonia in both nonobese and obese mice. Obese mice had greater lung injury compared with nonobese mice at 6 h after pneumonia. Leptin and insulin levels were higher in obese mice compared with nonobese mice, and obese mice with pneumonia had higher pulmonary STAT3 activation compared with nonobese mice.
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Affiliation(s)
- Lauren Bodilly
- Department of Pediatrics, University of Iowa, Iowa City, IA
| | - Lauren Williamson
- Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Kendra Howell
- Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
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13
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Gautier T, Fahet N, Tamanai-Shacoori Z, Oliviero N, Blot M, Sauvager A, Burel A, Gall SDL, Tomasi S, Blat S, Bousarghin L. Roseburia intestinalis Modulates PYY Expression in a New a Multicellular Model including Enteroendocrine Cells. Microorganisms 2022; 10:2263. [PMID: 36422333 PMCID: PMC9694292 DOI: 10.3390/microorganisms10112263] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 11/08/2022] [Accepted: 11/10/2022] [Indexed: 09/10/2024] Open
Abstract
The gut microbiota contributes to human health and disease; however, the mechanisms by which commensal bacteria interact with the host are still unclear. To date, a number of in vitro systems have been designed to investigate the host-microbe interactions. In most of the intestinal models, the enteroendocrine cells, considered as a potential link between gut bacteria and several human diseases, were missing. In the present study, we have generated a new model by adding enteroendocrine cells (ECC) of L-type (NCI-H716) to the one that we have previously described including enterocytes, mucus, and M cells. After 21 days of culture with the other cells, enteroendocrine-differentiated NCI-H716 cells showed neuropods at their basolateral side and expressed their specific genes encoding proglucagon (GCG) and chromogranin A (CHGA). We showed that this model could be stimulated by commensal bacteria playing a key role in health, Roseburia intestinalis and Bacteroides fragilis, but also by a pathogenic strain such as Salmonella Heidelberg. Moreover, using cell-free supernatants of B. fragilis and R. intestinalis, we have shown that R. intestinalis supernatant induced a significant increase in IL-8 and PYY but not in GCG gene expression, while B. fragilis had no impact. Our data indicated that R. intestinalis produced short chain fatty acids (SCFAs) such as butyrate whereas B. fragilis produced more propionate. However, these SCFAs were probably not the only metabolites implicated in PYY expression since butyrate alone had no effect. In conclusion, our new quadricellular model of gut epithelium could be an effective tool to highlight potential beneficial effects of bacteria or their metabolites, in order to develop new classes of probiotics.
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Affiliation(s)
- Thomas Gautier
- Institut NUMECAN, INSERM, Univ Rennes, INRAE, F-35000 Rennes, France
| | - Nelly Fahet
- Institut NUMECAN, INSERM, Univ Rennes, INRAE, F-35000 Rennes, France
| | | | - Nolwenn Oliviero
- Institut NUMECAN, INSERM, Univ Rennes, INRAE, F-35000 Rennes, France
| | - Marielle Blot
- ISCR (Institut des Sciences Chimiques de Rennes)-UMR CNRS 6226, Univ Rennes, CNRS, F-35000 Rennes, France
| | - Aurélie Sauvager
- ISCR (Institut des Sciences Chimiques de Rennes)-UMR CNRS 6226, Univ Rennes, CNRS, F-35000 Rennes, France
| | - Agnes Burel
- Plateforme Microscopie Electronique MRic/ISFR Biosit/Campus Santé, Univ Rennes, F-35000 Rennes, France
| | | | - Sophie Tomasi
- ISCR (Institut des Sciences Chimiques de Rennes)-UMR CNRS 6226, Univ Rennes, CNRS, F-35000 Rennes, France
| | - Sophie Blat
- Institut NUMECAN, INSERM, Univ Rennes, INRAE, F-35000 Rennes, France
| | - Latifa Bousarghin
- Institut NUMECAN, INSERM, Univ Rennes, INRAE, F-35000 Rennes, France
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14
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Li Y, Wu Y, Wu L, Qin L, Liu T. The effects of probiotic administration on patients with prediabetes: a meta-analysis and systematic review. J Transl Med 2022; 20:498. [PMID: 36324119 PMCID: PMC9632036 DOI: 10.1186/s12967-022-03695-y] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Revised: 09/26/2022] [Accepted: 10/06/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND This paper aimed to examine the effects of probiotics on eight factors in the prediabetic population by meta-analysis, namely, fasting blood glucose (FBG), glycated haemoglobin A1c (HbA1c), homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), and the mechanisms of action are summarized from the existing studies. METHODS Seven databases (PubMed, Web of Science, Embase, Cochrane Library, SinoMed, CNKI, and Wanfang Med) were searched until March 2022. Review Manager 5.4 was used for meta-analysis. The data were analysed using weighted mean differences (WMDs) or standardized mean differences (SMDs) under a fixed effect model to observe the efficacy of probiotic supplementation on the included indicators. RESULTS Seven publications with a total of 460 patients were included. According to the meta-analysis, probiotics were able to significantly decrease the levels of HbA1c (WMD, -0.07; 95% CI -0.11, -0.03; P = 0.001), QUICKI (WMD, 0.01; 95% CI 0.00, 0.02; P = 0.04), TC (SMD, -0.28; 95% CI -0.53, -0.22; P = 0.03), TG (SMD, -0.26; 95% CI -0.52, -0.01; P = 0.04), and LDL-C (WMD, -8.94; 95% CI -14.91, -2.97; P = 0.003) compared to levels in the placebo group. The effects on FBG (WMD, -0.53; 95% CI -2.31, 1.25; P = 0.56), HOMA-IR (WMD, -0.21; 95% CI -0.45, 0.04; P = 0.10), and HDL-C (WMD, 2.05; 95% CI -0.28, 4.38; P = 0.08) were not different from those of the placebo group. CONCLUSION The present study clearly indicated that probiotics may fulfil an important role in the regulation of HbA1c, QUICKI, TC, TG and LDL-C in patients with prediabetes. In addition, based on existing studies, we concluded that probiotics may regulate blood glucose homeostasis in a variety of ways. TRIAL REGISTRATION This meta-analysis has been registered at PROSPERO with ID: CRD42022321995.
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Affiliation(s)
- Ya Li
- Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, 100029, Beijing, China
| | - You Wu
- Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, 100029, Beijing, China
| | - Lili Wu
- Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, 100029, Beijing, China
| | - Lingling Qin
- Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, 100029, Beijing, China
| | - Tonghua Liu
- Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, 100029, Beijing, China.
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15
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Brubaker PL. The Molecular Determinants of Glucagon-like Peptide Secretion by the Intestinal L cell. Endocrinology 2022; 163:6717959. [PMID: 36156130 DOI: 10.1210/endocr/bqac159] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Indexed: 11/19/2022]
Abstract
The intestinal L cell secretes a diversity of biologically active hormones, most notably the glucagon-like peptides, GLP-1 and GLP-2. The highly successful introduction of GLP-1-based drugs into the clinic for the treatment of patients with type 2 diabetes and obesity, and of a GLP-2 analog for patients with short bowel syndrome, has led to the suggestion that stimulation of the endogenous secretion of these peptides may serve as a novel therapeutic approach in these conditions. Situated in the intestinal epithelium, the L cell demonstrates complex relationships with not only circulating, paracrine, and neural regulators, but also ingested nutrients and other factors in the lumen, most notably the microbiota. The integrated input from these numerous secretagogues results in a variety of temporal patterns in L cell secretion, ranging from minutes to 24 hours. This review combines the findings of traditional, physiological studies with those using newer molecular approaches to describe what is known and what remains to be elucidated after 5 decades of research on the intestinal L cell and its secreted peptides, GLP-1 and GLP-2.
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Affiliation(s)
- Patricia L Brubaker
- Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada
- Department of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada
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16
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Signaling pathways in obesity: mechanisms and therapeutic interventions. Signal Transduct Target Ther 2022; 7:298. [PMID: 36031641 PMCID: PMC9420733 DOI: 10.1038/s41392-022-01149-x] [Citation(s) in RCA: 170] [Impact Index Per Article: 56.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Revised: 07/26/2022] [Accepted: 08/08/2022] [Indexed: 12/19/2022] Open
Abstract
Obesity is a complex, chronic disease and global public health challenge. Characterized by excessive fat accumulation in the body, obesity sharply increases the risk of several diseases, such as type 2 diabetes, cardiovascular disease, and nonalcoholic fatty liver disease, and is linked to lower life expectancy. Although lifestyle intervention (diet and exercise) has remarkable effects on weight management, achieving long-term success at weight loss is extremely challenging, and the prevalence of obesity continues to rise worldwide. Over the past decades, the pathophysiology of obesity has been extensively investigated, and an increasing number of signal transduction pathways have been implicated in obesity, making it possible to fight obesity in a more effective and precise way. In this review, we summarize recent advances in the pathogenesis of obesity from both experimental and clinical studies, focusing on signaling pathways and their roles in the regulation of food intake, glucose homeostasis, adipogenesis, thermogenesis, and chronic inflammation. We also discuss the current anti-obesity drugs, as well as weight loss compounds in clinical trials, that target these signals. The evolving knowledge of signaling transduction may shed light on the future direction of obesity research, as we move into a new era of precision medicine.
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17
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do Rosário Caldas N, Braulio VB, Brasil MAA, Furtado VCS, de Carvalho DP, Cotrik EM, Dantas JR, Zajdenverg L. Binge eating disorder, frequency of depression, and systemic inflammatory state in individuals with obesity - A cross sectional study. ARCHIVES OF ENDOCRINOLOGY AND METABOLISM 2022; 66:489-497. [PMID: 35758834 PMCID: PMC10697643 DOI: 10.20945/2359-3997000000489] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Accepted: 03/07/2022] [Indexed: 06/15/2023]
Abstract
Introduction Binge eating disorder (BED) is the most prevalent eating disorder in individuals with obesity. Its association with factors that control hunger and satiety has not yet been elucidated. We evaluated whether levels of inflammatory markers, frequency of psychiatric comorbidities, and appetite-related hormones levels differ between individuals with obesity with and without BED. Subjects and methods The Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-5 - Clinician Version (SCID-5-CV), Binge Eating Scale, and Hospital Anxiety and Depression Scale were evaluated in 39 individuals with obesity. Plasma levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), leptin, ghrelin, and glucagon-like peptide-1 (GLP-1) were measured. Results Individuals of the BED group exhibited significantly higher percentages of altered eating patterns (hyperphagia, bingeing, post-dinner eating, feeling "stuffed", and emotional eating), higher depressive symptom scores and levels of leptin, CRP, and TNF-α, compared to those from the non-BED group. Logistic regression showed that BED was independently associated with depressive symptoms and CRP levels. Conclusion Individuals with obesity and BED showed greater psychiatric comorbidity, worse eating patterns and worse inflammatory profile than those without BED. BED should be assessed as an indicator of clinical severity in patients with obesity.
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Affiliation(s)
- Nelson do Rosário Caldas
- Universidade Federal do Rio de Janeiro, Serviço de Psiquiatria e Psicologia Médica, Rio de Janeiro, RJ, Brasil,
| | - Valeria Bender Braulio
- Universidade Federal do Rio de Janeiro, Serviço de Nutrologia, Rio de Janeiro, RJ, Brasil
| | - Marco Antônio Alves Brasil
- Universidade Federal do Rio de Janeiro, Serviço de Psiquiatria e Psicologia Médica, Rio de Janeiro, RJ, Brasil
| | | | - Denise Pires de Carvalho
- Universidade Federal do Rio de Janeiro, Instituto de Biofísica Carlos Chagas Filho, Rio de Janeiro, RJ, Brasil
| | - Ervin Michelstaedter Cotrik
- Universidade Federal do Rio de Janeiro, Serviço de Psiquiatria e Psicologia Médica, Rio de Janeiro, RJ, Brasil
| | - Joana Rodrigues Dantas
- Universidade Federal do Rio de Janeiro, Serviço de Nutrologia, Rio de Janeiro, RJ, Brasil
| | - Lenita Zajdenverg
- Universidade Federal do Rio de Janeiro, Serviço de Nutrologia, Rio de Janeiro, RJ, Brasil
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18
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Martchenko A, Biancolin AD, Martchenko SE, Brubaker PL. Nobiletin ameliorates high fat-induced disruptions in rhythmic glucagon-like peptide-1 secretion. Sci Rep 2022; 12:7271. [PMID: 35508494 PMCID: PMC9068808 DOI: 10.1038/s41598-022-11223-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Accepted: 04/20/2022] [Indexed: 02/06/2023] Open
Abstract
The incretin hormone glucagon-like peptide-1 (GLP-1) is secreted by the intestinal L cell in response to nutrient intake. However, GLP-1 secretion also follows a circadian rhythm which is disrupted by the saturated fatty acid palmitate in vitro and high-fat diet (HFD) feeding in vivo. The flavonoid nobiletin is a clock enhancer which improves metabolic homeostasis. Therefore, the aim of this study was to elucidate whether and how nobiletin mitigates the negative effects of palmitate and HFD-feeding on rhythmic GLP-1 release. Pre-treatment of murine GLUTag L cells with palmitate dampened the GLP-1 secretory response at the normal peak of secretion, while nobiletin co-treatment restored GLP-1 secretion and upregulated the ‘metabolic pathway’ transcriptome. Mice fed a HFD also lost their GLP-1 secretory rhythm in association with markedly increased GLP-1 levels and upregulation of L cell transcriptional pathways related to ‘sensing’ and ‘transducing’ cellular stimuli at the normal peak of GLP-1 release. Nobiletin co-administration reduced GLP-1 levels to more physiological levels and upregulated L cell ‘oxidative metabolism’ transcriptional pathways. Furthermore, nobiletin improved colonic microbial 16S rRNA gene diversity and reduced the levels of Proteobacteria in HFD-fed mice. Collectively, this study establishes that nobiletin improves the normal rhythm in GLP-1 secretion following fat-induced disruption.
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Affiliation(s)
- Alexandre Martchenko
- Department of Physiology, University of Toronto, Rm 3366 Medical Sciences Building, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada
| | - Andrew D Biancolin
- Department of Physiology, University of Toronto, Rm 3366 Medical Sciences Building, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada
| | - Sarah E Martchenko
- Department of Physiology, University of Toronto, Rm 3366 Medical Sciences Building, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada
| | - Patricia L Brubaker
- Department of Physiology, University of Toronto, Rm 3366 Medical Sciences Building, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada. .,Department of Medicine, University of Toronto, Toronto, ON, Canada.
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19
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Bastos RMC, Simplício-Filho A, Sávio-Silva C, Oliveira LFV, Cruz GNF, Sousa EH, Noronha IL, Mangueira CLP, Quaglierini-Ribeiro H, Josefi-Rocha GR, Rangel ÉB. Fecal Microbiota Transplant in a Pre-Clinical Model of Type 2 Diabetes Mellitus, Obesity and Diabetic Kidney Disease. Int J Mol Sci 2022; 23:3842. [PMID: 35409202 PMCID: PMC8998923 DOI: 10.3390/ijms23073842] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Revised: 01/31/2022] [Accepted: 02/07/2022] [Indexed: 01/27/2023] Open
Abstract
Diabetes mellitus (DM) burden encompasses diabetic kidney disease (DKD), the leading cause of end-stage renal disease worldwide. Despite compelling evidence indicating that pharmacological intervention curtails DKD progression, the search for non-pharmacological strategies can identify novel targets for drug development against metabolic diseases. One of those emergent strategies comprises the modulation of the intestinal microbiota through fecal transplant from healthy donors. This study sought to investigate the benefits of fecal microbiota transplant (FMT) on functional and morphological parameters in a preclinical model of type 2 DM, obesity, and DKD using BTBRob/ob mice. These animals develop hyperglycemia and albuminuria in a time-dependent manner, mimicking DKD in humans. Our main findings unveiled that FMT prevented body weight gain, reduced albuminuria and tumor necrosis factor-α (TNF-α) levels within the ileum and ascending colon, and potentially ameliorated insulin resistance in BTBRob/ob mice. Intestinal structural integrity was maintained. Notably, FMT was associated with the abundance of the succinate-consuming Odoribacteraceae bacteria family throughout the intestine. Collectively, our data pointed out the safety and efficacy of FMT in a preclinical model of type 2 DM, obesity, and DKD. These findings provide a basis for translational research on intestinal microbiota modulation and testing its therapeutic potential combined with current treatment for DM.
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Affiliation(s)
- Rosana M. C. Bastos
- Hospital Israelita Albert Einstein, São Paulo 05652-900, SP, Brazil; (R.M.C.B.); (A.S.-F.); (C.S.-S.); (E.H.S.); (C.L.P.M.); (H.Q.-R.); (G.R.J.-R.)
| | - Antônio Simplício-Filho
- Hospital Israelita Albert Einstein, São Paulo 05652-900, SP, Brazil; (R.M.C.B.); (A.S.-F.); (C.S.-S.); (E.H.S.); (C.L.P.M.); (H.Q.-R.); (G.R.J.-R.)
| | - Christian Sávio-Silva
- Hospital Israelita Albert Einstein, São Paulo 05652-900, SP, Brazil; (R.M.C.B.); (A.S.-F.); (C.S.-S.); (E.H.S.); (C.L.P.M.); (H.Q.-R.); (G.R.J.-R.)
| | | | | | - Eliza H. Sousa
- Hospital Israelita Albert Einstein, São Paulo 05652-900, SP, Brazil; (R.M.C.B.); (A.S.-F.); (C.S.-S.); (E.H.S.); (C.L.P.M.); (H.Q.-R.); (G.R.J.-R.)
| | - Irene L. Noronha
- Division of Nephrology, School of Medicine, University of São Paulo, São Paulo 01246-903, SP, Brazil;
| | - Cristóvão L. P. Mangueira
- Hospital Israelita Albert Einstein, São Paulo 05652-900, SP, Brazil; (R.M.C.B.); (A.S.-F.); (C.S.-S.); (E.H.S.); (C.L.P.M.); (H.Q.-R.); (G.R.J.-R.)
| | - Heloísa Quaglierini-Ribeiro
- Hospital Israelita Albert Einstein, São Paulo 05652-900, SP, Brazil; (R.M.C.B.); (A.S.-F.); (C.S.-S.); (E.H.S.); (C.L.P.M.); (H.Q.-R.); (G.R.J.-R.)
| | - Gleice R. Josefi-Rocha
- Hospital Israelita Albert Einstein, São Paulo 05652-900, SP, Brazil; (R.M.C.B.); (A.S.-F.); (C.S.-S.); (E.H.S.); (C.L.P.M.); (H.Q.-R.); (G.R.J.-R.)
| | - Érika B. Rangel
- Hospital Israelita Albert Einstein, São Paulo 05652-900, SP, Brazil; (R.M.C.B.); (A.S.-F.); (C.S.-S.); (E.H.S.); (C.L.P.M.); (H.Q.-R.); (G.R.J.-R.)
- Nephrology Division, Federal University of São Paulo, São Paulo 04023-900, SP, Brazil
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20
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Antidiabetic Effects of Pediococcus acidilactici pA1c on HFD-Induced Mice. Nutrients 2022; 14:nu14030692. [PMID: 35277051 PMCID: PMC8839473 DOI: 10.3390/nu14030692] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 01/28/2022] [Accepted: 01/28/2022] [Indexed: 12/11/2022] Open
Abstract
Prediabetes (PreD), which is associated with impaired glucose tolerance and fasting blood glucose, is a potential risk factor for type 2 diabetes mellitus (T2D). Growing evidence suggests the role of the gastrointestinal microbiota in both PreD and T2D, which opens the possibility for a novel nutritional approach, based on probiotics, for improving glucose regulation and delaying disease progression of PreD to T2D. In this light, the present study aimed to assess the antidiabetic properties of Pediococcus acidilactici (pA1c) in a murine model of high-fat diet (HFD)-induced T2D. For that purpose, C57BL/6 mice were given HFD enriched with either probiotic (1 × 1010 CFU/day) or placebo for 12 weeks. We determined body weight, fasting blood glucose, glucose tolerance, HOMA-IR and HOMA-β index, C-peptide, GLP-1, leptin, and lipid profile. We also measured hepatic gene expression (G6P, PEPCK, GCK, IL-1β, and IL-6) and examined pancreatic and intestinal histology (% of GLP-1+ cells, % of goblet cells and villus length). We found that pA1c supplementation significantly attenuated body weight gain, mitigated glucose dysregulation by reducing fasting blood glucose levels, glucose tolerance test, leptin levels, and insulin resistance, increased C-peptide and GLP-1 levels, enhanced pancreatic function, and improved intestinal histology. These findings indicate that pA1c improved HFD-induced T2D derived insulin resistance and intestinal histology, as well as protected from body weight increase. Together, our study proposes that pA1c may be a promising new dietary management strategy to improve metabolic disorders in PreD and T2D.
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21
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Dimas A, Politi A, Papaioannou G, Barber TM, Weickert MO, Grammatopoulos DK, Kumar S, Kalantaridou S, Valsamakis G. The Gestational Effects of Maternal Appetite Axis Molecules on Fetal Growth, Metabolism and Long-Term Metabolic Health: A Systematic Review. Int J Mol Sci 2022; 23:ijms23020695. [PMID: 35054881 PMCID: PMC8776066 DOI: 10.3390/ijms23020695] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Revised: 01/02/2022] [Accepted: 01/04/2022] [Indexed: 12/12/2022] Open
Abstract
Increased maternal food intake is considered a normal pregnancy adjustment. However, the overavailability of nutrients may lead to dysregulated fetal development and increased adiposity, with long-lasting effects on offspring in later life. Several gut-hormone molecules regulate maternal appetite, with both their orexigenic and anorectic effects being in a state of sensitive equilibrium. The aim of this manuscript is to systematically review literature on the effects of maternal gut-hormone molecules on fetal growth and metabolism, birth weight and the later metabolic health of offspring. Maternal serum ghrelin, leptin, IGF-1 and GLP-1 appear to influence fetal growth; however, a lack of consistent and strong correlations of maternal appetite axis hormones with birth weight and the concomitant correlation with fetal and birth waist circumference may suggest that these molecules primarily mediate fetal energy deposition mechanisms, preparing the fetus for survival after birth. Dysregulated intrauterine environments seem to have detrimental, sex-dependent effects on fetal energy stores, affecting not only fetal growth, fat mass deposition and birth weight, but also future metabolic and endocrine wellbeing of offspring.
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Affiliation(s)
- Angelos Dimas
- 3rd University Department of Obstetrics & Gynecology, Attikon University Hospital, Medical School of Athens, Ethnikon and Kapodistriakon University of Athens, 12462 Athens, Greece; (G.P.); (S.K.)
- Correspondence:
| | - Anastasia Politi
- Nephrology Department, University Hospital of Ioannina, Stavros Niarchos Ave., 45500 Ioannina, Greece;
| | - George Papaioannou
- 3rd University Department of Obstetrics & Gynecology, Attikon University Hospital, Medical School of Athens, Ethnikon and Kapodistriakon University of Athens, 12462 Athens, Greece; (G.P.); (S.K.)
| | - Thomas M. Barber
- Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire, Clifford Bridge Road, Coventry CV2 2DX, UK; (T.M.B.); (M.O.W.); (S.K.)
| | - Martin O. Weickert
- Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire, Clifford Bridge Road, Coventry CV2 2DX, UK; (T.M.B.); (M.O.W.); (S.K.)
| | - Dimitris K. Grammatopoulos
- Institute of Precision Diagnostics and Translational Medicine, Pathology, University Hospitals Coventry and Warwickshire (UHCW) NHS Trust, Coventry CV2 2DX, UK; (D.K.G.); (G.V.)
| | - Sudhesh Kumar
- Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism, University Hospitals Coventry and Warwickshire, Clifford Bridge Road, Coventry CV2 2DX, UK; (T.M.B.); (M.O.W.); (S.K.)
| | - Sophia Kalantaridou
- 3rd University Department of Obstetrics & Gynecology, Attikon University Hospital, Medical School of Athens, Ethnikon and Kapodistriakon University of Athens, 12462 Athens, Greece; (G.P.); (S.K.)
- Reproductive Endocrinology Unit, 3rd University Department of Obstetrics & Gynecology, Attikon University Hospital, Medical School of Athens, 12462 Athens, Greece
| | - Georgios Valsamakis
- Institute of Precision Diagnostics and Translational Medicine, Pathology, University Hospitals Coventry and Warwickshire (UHCW) NHS Trust, Coventry CV2 2DX, UK; (D.K.G.); (G.V.)
- 2nd University Department of Obstetrics & Gynecology, Aretaieion University Hospital, Medical School of Athens, Ethnikon and Kapodistriakon University of Athens, 12462 Athens, Greece
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22
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Abstract
Cross-talk between peripheral tissues is essential to ensure the coordination of nutrient intake with disposition during the feeding period, thereby preventing metabolic disease. This mini-review considers the interactions between the key peripheral tissues that constitute the metabolic clock, each of which is considered in a separate mini-review in this collation of articles published in Endocrinology in 2020 and 2021, by Martchenko et al (Circadian rhythms and the gastrointestinal tract: relationship to metabolism and gut hormones); Alvarez et al (The microbiome as a circadian coordinator of metabolism); Seshadri and Doucette (Circadian regulation of the pancreatic beta cell); McCommis et al (The importance of keeping time in the liver); Oosterman et al (The circadian clock, shift work, and tissue-specific insulin resistance); and Heyde et al (Contributions of white and brown adipose tissues to the circadian regulation of energy metabolism). The use of positive- and negative-feedback signals, both hormonal and metabolic, between these tissues ensures that peripheral metabolic pathways are synchronized with the timing of food intake, thus optimizing nutrient disposition and preventing metabolic disease. Collectively, these articles highlight the critical role played by the circadian clock in maintaining metabolic homeostasis.
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Affiliation(s)
- Patricia L Brubaker
- Department of Physiology, University of Toronto, Toronto, Ontario M5S 1A8Canada
- Department of Medicine, University of Toronto, Toronto, Ontario M5S 1A8Canada
- Correspondence: P. L. Brubaker, PhD, Departments of Physiology and Medicine, University of Toronto, Medical Sciences Bldg, Rm 3366, 1 King’s College Cir, Toronto, ON M5S 1A8, Canada.
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23
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Desmet L, Thijs T, Segers A, Verbeke K, Depoortere I. Chronodisruption by chronic jetlag impacts metabolic and gastrointestinal homeostasis in male mice. Acta Physiol (Oxf) 2021; 233:e13703. [PMID: 34107165 DOI: 10.1111/apha.13703] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Revised: 05/28/2021] [Accepted: 06/04/2021] [Indexed: 01/20/2023]
Abstract
AIM Chronodisruption desynchronizes peripheral clocks and leads to metabolic diseases. Feeding cues are important synchronizers of peripheral clocks and influence rhythmic oscillations in intestinal microbiota and their metabolites. We investigated whether chronic jetlag, mimicking frequent time zone travelling, affected the diurnal fluctuations in faecal short-chain fatty acid (SCFA) levels, that feed back to the gut clock to regulate rhythmicity in gut function. METHODS Rhythms in faecal SCFAs levels and in the expression of clock genes and epithelial markers were measured in the colonic mucosa of control and jetlagged mice. The entraining effect of SCFAs on the rhythm in clock gene mRNA expression was studied in primary colonic crypts. The role of the circadian clock in epithelial marker expression was studied in Arntl-/- mice. RESULTS Chronic jetlag increased body weight gain and abolished the day/night food intake pattern which resulted in a phase-delay in the rhythm of faecal SCFAs that paralleled the shift in the expression of mucosal clock genes. This effect was mimicked by stimulation of primary colonic crypts from control mice with SCFAs. Jetlag abolished the rhythm in Tnfα, proglucagon and ghrelin expression but not in the expression of tight junction markers. Only a dampening in plasma glucagon-like peptide-1 but not in ghrelin levels was observed. Rhythms in ghrelin but not proglucagon mRNA expression were abolished in Arntl-/- mice. CONCLUSION The altered food intake pattern during chronodisruption corresponds with the changes in rhythmicity of SCFA levels that entrain clock genes to affect rhythms in mRNA expression of gut epithelial markers.
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Affiliation(s)
- Louis Desmet
- Translational Research Center for Gastrointestinal Disorders KU Leuven Leuven Belgium
| | - Theo Thijs
- Translational Research Center for Gastrointestinal Disorders KU Leuven Leuven Belgium
| | - Anneleen Segers
- Translational Research Center for Gastrointestinal Disorders KU Leuven Leuven Belgium
| | - Kristin Verbeke
- Translational Research Center for Gastrointestinal Disorders KU Leuven Leuven Belgium
| | - Inge Depoortere
- Translational Research Center for Gastrointestinal Disorders KU Leuven Leuven Belgium
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24
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Stahel P, Xiao C, Nahmias A, Tian L, Lewis GF. Multi-organ Coordination of Lipoprotein Secretion by Hormones, Nutrients and Neural Networks. Endocr Rev 2021; 42:815-838. [PMID: 33743013 PMCID: PMC8599201 DOI: 10.1210/endrev/bnab008] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Indexed: 12/15/2022]
Abstract
Plasma triglyceride-rich lipoproteins (TRL), particularly atherogenic remnant lipoproteins, contribute to atherosclerotic cardiovascular disease. Hypertriglyceridemia may arise in part from hypersecretion of TRLs by the liver and intestine. Here we focus on the complex network of hormonal, nutritional, and neuronal interorgan communication that regulates secretion of TRLs and provide our perspective on the relative importance of these factors. Hormones and peptides originating from the pancreas (insulin, glucagon), gut [glucagon-like peptide 1 (GLP-1) and 2 (GLP-2), ghrelin, cholecystokinin (CCK), peptide YY], adipose tissue (leptin, adiponectin) and brain (GLP-1) modulate TRL secretion by receptor-mediated responses and indirectly via neural networks. In addition, the gut microbiome and bile acids influence lipoprotein secretion in humans and animal models. Several nutritional factors modulate hepatic lipoprotein secretion through effects on the central nervous system. Vagal afferent signaling from the gut to the brain and efferent signals from the brain to the liver and gut are modulated by hormonal and nutritional factors to influence TRL secretion. Some of these factors have been extensively studied and shown to have robust regulatory effects whereas others are "emerging" regulators, whose significance remains to be determined. The quantitative importance of these factors relative to one another and relative to the key regulatory role of lipid availability remains largely unknown. Our understanding of the complex interorgan regulation of TRL secretion is rapidly evolving to appreciate the extensive hormonal, nutritional, and neural signals emanating not only from gut and liver but also from the brain, pancreas, and adipose tissue.
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Affiliation(s)
- Priska Stahel
- Division of Endocrinology and Metabolism, Departments of Medicine and Physiology, Banting & Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada
| | - Changting Xiao
- Department of Anatomy, Physiology and Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | - Avital Nahmias
- Division of Endocrinology and Metabolism, Departments of Medicine and Physiology, Banting & Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada
| | - Lili Tian
- Division of Endocrinology and Metabolism, Departments of Medicine and Physiology, Banting & Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada
| | - Gary Franklin Lewis
- Division of Endocrinology and Metabolism, Departments of Medicine and Physiology, Banting & Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada
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25
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Redondo-Puente M, Mateos R, Seguido MA, García-Cordero J, González S, Tarradas RM, Bravo-Clemente L, Sarriá B. Appetite and Satiety Effects of the Acute and Regular Consumption of Green Coffee Phenols and Green Coffee Phenol/Oat β-Glucan Nutraceuticals in Subjects with Overweight and Obesity. Foods 2021; 10:2511. [PMID: 34828792 PMCID: PMC8622553 DOI: 10.3390/foods10112511] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Revised: 09/29/2021] [Accepted: 10/17/2021] [Indexed: 12/17/2022] Open
Abstract
Green coffee has weight management properties, yet its effects on appetite and satiety remain unclear as few, mainly acute, studies perform objective measurements. Therefore, the influence on appetite/satiety of acute and regular consumption of two nutraceuticals, a decaffeinated green coffee phenolic extract (GC) alone or combined with oat β-glucans (GC/BG), with known satiating properties, has been analysed subjectively using visual analog scales (VAS) and objectively measuring actual food intake and postprandial appetite and satiety hormones. A randomised, cross-over, blind trial was carried out in 29 overweight volunteers who consumed GC or GC/BG twice a day for 8 weeks. After acute (day = 0) and regular consumption (day = 56) of the nutraceuticals, satiety was measured at 30, 60, 90, 150, and 210 min, as well as food intake at breakfast (30 min) and lunch (300 min). Additionally, in a subgroup of participants (n = 9), cholecystokinin, peptide-YY, glucagon-like-peptide-1, ghrelin and leptin concentrations were analysed in blood samples taken at the same time-points. According to VAS results, GC/BG reduced hunger more efficiently than GC. However, there were no statistically significant differences in food intake. Comparing the effects of the acute consumption of GC/BG and GC, leptin concentration at 150 min was higher after GC/BG intake vs. GC. Moreover, when comparing the effects of regularly consuming the two nutraceuticals, maximum ghrelin level decreased with GC/BG vs. GC. In conclusion, acute and regular effects of the nutraceuticals on appetite/satiety differed, and subjective and objective results partially agreed; GC/BG may reduce hunger more efficiently than GC.
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Affiliation(s)
| | | | | | | | | | | | | | - Beatriz Sarriá
- Department of Metabolism and Nutrition, Institute of Food Science, Technology and Nutrition (ICTAN-CSIC), Spanish National Research Council (CSIC), José Antonio Nováis 10, 28040 Madrid, Spain; (M.R.-P.); (R.M.); (M.A.S.); (J.G.-C.); (S.G.); (R.M.T.); (L.B.-C.)
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26
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Morrow NM, Hanson AA, Mulvihill EE. Distinct Identity of GLP-1R, GLP-2R, and GIPR Expressing Cells and Signaling Circuits Within the Gastrointestinal Tract. Front Cell Dev Biol 2021; 9:703966. [PMID: 34660576 PMCID: PMC8511495 DOI: 10.3389/fcell.2021.703966] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Accepted: 08/16/2021] [Indexed: 12/17/2022] Open
Abstract
Enteroendocrine cells directly integrate signals of nutrient content within the gut lumen with distant hormonal responses and nutrient disposal via the production and secretion of peptides, including glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1) and glucagon-like peptide 2 (GLP-2). Given their direct and indirect control of post-prandial nutrient uptake and demonstrated translational relevance for the treatment of type 2 diabetes, malabsorption and cardiometabolic disease, there is significant interest in the locally engaged circuits mediating these metabolic effects. Although several specific populations of cells in the intestine have been identified to express endocrine receptors, including intraepithelial lymphocytes (IELs) and αβ and γδ T-cells (Glp1r+) and smooth muscle cells (Glp2r+), the definitive cellular localization and co-expression, particularly in regards to the Gipr remain elusive. Here we review the current state of the literature and evaluate the identity of Glp1r, Glp2r, and Gipr expressing cells within preclinical and clinical models. Further elaboration of our understanding of the initiating G-protein coupled receptor (GPCR) circuits engaged locally within the intestine and how they become altered with high-fat diet feeding can offer insight into the dysregulation observed in obesity and diabetes.
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Affiliation(s)
- Nadya M Morrow
- Energy Substrate Laboratory, University of Ottawa Heart Institute, Ottawa, ON, Canada.,Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada
| | - Antonio A Hanson
- Energy Substrate Laboratory, University of Ottawa Heart Institute, Ottawa, ON, Canada.,Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada
| | - Erin E Mulvihill
- Energy Substrate Laboratory, University of Ottawa Heart Institute, Ottawa, ON, Canada.,Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada.,Montreal Diabetes Research Center CRCHUM-Pavillion R, Montreal, QC, Canada.,Centre for Infection, Immunity and Inflammation, University of Ottawa, Ottawa, ON, Canada
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27
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Yaribeygi H, Maleki M, Atkin SL, Jamialahmadi T, Sahebkar A. Impact of Incretin-Based Therapies on Adipokines and Adiponectin. J Diabetes Res 2021; 2021:3331865. [PMID: 34660808 PMCID: PMC8516550 DOI: 10.1155/2021/3331865] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Accepted: 09/27/2021] [Indexed: 12/14/2022] Open
Abstract
Adipokines are a family of hormones and cytokines with both pro- and anti-inflammatory effects released into the circulation to exert their hormonal effects. Adipokines are closely involved in most metabolic pathways and play an important modulatory role in lipid and carbohydrate homeostasis as they are involved in the pathophysiology of most metabolic disorders. Incretin-based therapy is a newly introduced class of antidiabetic drugs that restores euglycemia through several cellular processes; however, its effect on adipokines expression/secretion is not fully understood. In this review, we propose that incretin-based therapy may function through adipokine modulation that may result in pharmacologic properties beyond their direct antidiabetic effects, resulting in better management of diabetes and diabetes-related complications.
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Affiliation(s)
- Habib Yaribeygi
- Research Center of Physiology, Semnan University of Medical Sciences, Semnan, Iran
| | - Mina Maleki
- Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Tannaz Jamialahmadi
- Department of Food Science and Technology, Quchan Branch, Islamic Azad University, Quchan, Iran
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirhossein Sahebkar
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
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28
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Lee LC, Hou YC, Hsieh YY, Chen YH, Shen YC, Lee IJ, Monica Shih MC, Hou WC, Liu HK. Dietary supplementation of rutin and rutin-rich buckwheat elevates endogenous glucagon-like peptide 1 levels to facilitate glycemic control in type 2 diabetic mice. J Funct Foods 2021; 85:104653. [DOI: 10.1016/j.jff.2021.104653] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
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29
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Mooldijk SS, Ikram MK, Ikram MA. Adiponectin, leptin and resistin and the risk of dementia. J Gerontol A Biol Sci Med Sci 2021; 77:1245-1249. [PMID: 34525197 PMCID: PMC9159665 DOI: 10.1093/gerona/glab267] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Indexed: 02/04/2023] Open
Abstract
Background Adipokines are hormones secreted by adipose tissue with roles in energy homeostasis and regulation of metabolism. Their dysregulation is suggested to contribute to the increased risk of dementia seen with midlife obesity, but longitudinal studies investigating this are scarce. We determined the association between plasma levels of adiponectin, leptin, and resistin with the risk of dementia. Methods We performed a case–cohort study embedded in the prospective, population-based Rotterdam Study. Plasma levels of the adiponectin, leptin, and resistin were measured at baseline (1997–1999) in a random subcohort of 945 participants without dementia, and additionally in 177 participants, who were diagnosed with dementia during follow-up (until January 1, 2018). Results Higher levels of leptin and resistin were associated with a decreased risk of dementia (adjusted hazard ratio [95% confidence interval] per SD increase of log-transformed values: 0.85 [0.72–1.00] for leptin; 0.82 [0.71–0.95] for resistin). The association of leptin with dementia was further modified by body mass index and by APOE ε4 carrier status. Adiponectin levels were not associated with the risk of dementia. Conclusions These findings support the hypothesis that adipokines have a role in the pathophysiology of dementia. Future studies are warranted to confirm the findings and to explore the underlying mechanisms.
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Affiliation(s)
- Sanne S Mooldijk
- Department of Epidemiology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - M Kamran Ikram
- Department of Epidemiology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands.,Department of Neurology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - M Arfan Ikram
- Department of Epidemiology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands
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30
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Kabahizi A, Wallace B, Lieu L, Chau D, Dong Y, Hwang ES, Williams KW. Glucagon-like peptide-1 (GLP-1) signalling in the brain: From neural circuits and metabolism to therapeutics. Br J Pharmacol 2021; 179:600-624. [PMID: 34519026 PMCID: PMC8820188 DOI: 10.1111/bph.15682] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Revised: 08/23/2021] [Accepted: 08/27/2021] [Indexed: 12/18/2022] Open
Abstract
Glucagon‐like‐peptide‐1 (GLP‐1) derived from gut enteroendocrine cells and a discrete population of neurons in the caudal medulla acts through humoral and neural pathways to regulate satiety, gastric motility and pancreatic endocrine function. These physiological attributes contribute to GLP‐1 having a potent therapeutic action in glycaemic regulation and chronic weight management. In this review, we provide an overview of the neural circuits targeted by endogenous versus exogenous GLP‐1 and related drugs. We also highlight candidate subpopulations of neurons and cellular mechanisms responsible for the acute and chronic effects of GLP‐1 and GLP‐1 receptor agonists on energy balance and glucose metabolism. Finally, we present potential future directions to translate these findings towards the development of effective therapies for treatment of metabolic disease.
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Affiliation(s)
- Anita Kabahizi
- Department of Internal Medicine, Center for Hypothalamic Research, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA
| | - Briana Wallace
- Department of Internal Medicine, Center for Hypothalamic Research, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA
| | - Linh Lieu
- Department of Internal Medicine, Center for Hypothalamic Research, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA
| | - Dominic Chau
- Department of Internal Medicine, Center for Hypothalamic Research, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA
| | - Yanbin Dong
- Department of Internal Medicine, Center for Hypothalamic Research, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA
| | - Eun-Sang Hwang
- Department of Internal Medicine, Center for Hypothalamic Research, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA
| | - Kevin W Williams
- Department of Internal Medicine, Center for Hypothalamic Research, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA
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31
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Comparison of metabolic beneficial effects of Liraglutide and Semaglutide in male C57BL/6J mice. Can J Diabetes 2021; 46:216-224.e2. [DOI: 10.1016/j.jcjd.2021.08.012] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Revised: 08/10/2021] [Accepted: 08/27/2021] [Indexed: 11/29/2022]
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32
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Mechanisms of Glucose Absorption in the Small Intestine in Health and Metabolic Diseases and Their Role in Appetite Regulation. Nutrients 2021; 13:nu13072474. [PMID: 34371983 PMCID: PMC8308647 DOI: 10.3390/nu13072474] [Citation(s) in RCA: 57] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Revised: 07/13/2021] [Accepted: 07/16/2021] [Indexed: 12/11/2022] Open
Abstract
The worldwide prevalence of metabolic diseases such as obesity, metabolic syndrome and type 2 diabetes shows an upward trend in recent decades. A characteristic feature of these diseases is hyperglycemia which can be associated with hyperphagia. Absorption of glucose in the small intestine physiologically contributes to the regulation of blood glucose levels, and hence, appears as a putative target for treatment of hyperglycemia. In fact, recent progress in understanding the molecular and cellular mechanisms of glucose absorption in the gut and its reabsorption in the kidney helped to develop a new strategy of diabetes treatment. Changes in blood glucose levels are also involved in regulation of appetite, suggesting that glucose absorption may be relevant to hyperphagia in metabolic diseases. In this review we discuss the mechanisms of glucose absorption in the small intestine in physiological conditions and their alterations in metabolic diseases as well as their relevance to the regulation of appetite. The key role of SGLT1 transporter in intestinal glucose absorption in both physiological conditions and in diabetes was clearly established. We conclude that although inhibition of small intestinal glucose absorption represents a valuable target for the treatment of hyperglycemia, it is not always suitable for the treatment of hyperphagia. In fact, independent regulation of glucose absorption and appetite requires a more complex approach for the treatment of metabolic diseases.
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Verbeure W, van Goor H, Mori H, van Beek AP, Tack J, van Dijk PR. The Role of Gasotransmitters in Gut Peptide Actions. Front Pharmacol 2021; 12:720703. [PMID: 34354597 PMCID: PMC8329365 DOI: 10.3389/fphar.2021.720703] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Accepted: 07/07/2021] [Indexed: 12/31/2022] Open
Abstract
Although gasotransmitters nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S) receive a bad connotation; in low concentrations these play a major governing role in local and systemic blood flow, stomach acid release, smooth muscles relaxations, anti-inflammatory behavior, protective effect and more. Many of these physiological processes are upstream regulated by gut peptides, for instance gastrin, cholecystokinin, secretin, motilin, ghrelin, glucagon-like peptide 1 and 2. The relationship between gasotransmitters and gut hormones is poorly understood. In this review, we discuss the role of NO, CO and H2S on gut peptide release and functioning, and whether manipulation by gasotransmitter substrates or specific blockers leads to physiological alterations.
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Affiliation(s)
- Wout Verbeure
- Translational Research Center for Gastrointestinal Disorders, KU Leuven, Leuven, Belgium
| | - Harry van Goor
- Departement of Endocrinology, University Medical Center Groningen, Groningen, Netherlands
| | - Hideki Mori
- Translational Research Center for Gastrointestinal Disorders, KU Leuven, Leuven, Belgium
| | - André P. van Beek
- Departement of Endocrinology, University Medical Center Groningen, Groningen, Netherlands
| | - Jan Tack
- Translational Research Center for Gastrointestinal Disorders, KU Leuven, Leuven, Belgium
| | - Peter R. van Dijk
- Departement of Endocrinology, University Medical Center Groningen, Groningen, Netherlands
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Pavlisova J, Horakova O, Kalendova V, Buresova J, Bardova K, Holendova B, Plecita-Hlavata L, Vackova S, Windrichova J, Topolcan O, Kopecky J, Rossmeisl M. Chronic n-3 fatty acid intake enhances insulin response to oral glucose and elevates GLP-1 in high-fat diet-fed obese mice. Food Funct 2021; 11:9764-9775. [PMID: 33078809 DOI: 10.1039/d0fo01942a] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
n-3 polyunsaturated fatty acids (PUFA) can exert beneficial effects on glucose homeostasis, especially in obese rodents. Gut incretin hormones regulate glucose and lipid homeostasis, but their involvement in the above effects is not entirely clear. This study aims to assess the effects of chronic n-3 PUFA administration on the insulin and incretin responses in C57BL/6N obese male mice subjected to oral glucose tolerance test (oGTT) after 8 weeks of feeding a corn-oil-based high-fat diet (cHF). The weight gain and adiposity were partially reduced in mice fed cHF in which some of the corn oil was replaced with n-3 PUFA concentrate containing ∼60% DHA and EPA in a 3 : 1 ratio. In addition, these mice had improved glucose tolerance, which was consistent with an increased insulin response to oral glucose and plasma glucagon-like peptide-1 (GLP-1) levels. While the stimulatory effects of n-3 PUFA on GLP-1 levels could not be attributed to changes in intestinal or plasma dipeptidyl peptidase-4 activity, their beneficial effects on glucose tolerance were abolished when mice were pretreated with the GLP-1 receptor antagonist exendin 9-39. Moreover, chronic n-3 PUFA intake prevented the detrimental effects of cHF feeding on glucose-stimulated insulin secretion in the pancreatic islets. Collectively, our data suggest that n-3 PUFA may modulate postprandial glucose metabolism in obese mice through a GLP-1-based mechanism. The significance of these findings in terms of the effective DHA and EPA ratio of the n-3 PUFA concentrate as well as the effect of n-3 PUFA in humans requires further research.
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Affiliation(s)
- Jana Pavlisova
- Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic.
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35
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Heiss CN, Mannerås-Holm L, Lee YS, Serrano-Lobo J, Håkansson Gladh A, Seeley RJ, Drucker DJ, Bäckhed F, Olofsson LE. The gut microbiota regulates hypothalamic inflammation and leptin sensitivity in Western diet-fed mice via a GLP-1R-dependent mechanism. Cell Rep 2021; 35:109163. [PMID: 34038733 DOI: 10.1016/j.celrep.2021.109163] [Citation(s) in RCA: 63] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Revised: 04/06/2021] [Accepted: 04/29/2021] [Indexed: 12/14/2022] Open
Abstract
Mice lacking a microbiota are protected from diet-induced obesity. Previous studies have shown that feeding a Western diet causes hypothalamic inflammation, which in turn can lead to leptin resistance and weight gain. Here, we show that wild-type (WT) mice with depleted gut microbiota, i.e., germ-free (GF) and antibiotic-treated mice, have elevated levels of glucagon-like peptide-1 (GLP-1), are protected against diet-induced hypothalamic inflammation, and have enhanced leptin sensitivity when fed a Western diet. Using GLP-1 receptor (GLP-1R)-deficient mice and pharmacological inhibition of the GLP-1R in WT mice, we demonstrate that intact GLP-1R signaling is required for preventing hypothalamic inflammation and enhancing leptin sensitivity. Furthermore, we show that astrocytes express the GLP-1R, and deletion of the receptor in glial fibrillary acidic protein (GFAP)-expressing cells diminished the antibiotic-induced protection against diet-induced hypothalamic inflammation. Collectively, our results suggest that depletion of the gut microbiota attenuates diet-induced hypothalamic inflammation and enhances leptin sensitivity via GLP-1R-dependent mechanisms.
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Affiliation(s)
- Christina N Heiss
- Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, 41345 Gothenburg, Sweden
| | - Louise Mannerås-Holm
- Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, 41345 Gothenburg, Sweden
| | - Ying Shiuan Lee
- Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, 41345 Gothenburg, Sweden
| | - Julia Serrano-Lobo
- Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, 41345 Gothenburg, Sweden
| | - Anna Håkansson Gladh
- Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, 41345 Gothenburg, Sweden
| | - Randy J Seeley
- Department of Surgery, University of Michigan Medical School, Ann Arbor, MI 48109, USA
| | - Daniel J Drucker
- Department of Medicine, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, ON M5G 1X5, Canada
| | - Fredrik Bäckhed
- Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, 41345 Gothenburg, Sweden; Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Receptology and Enteroendocrinology, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; Department of Clinical Physiology, Region Västra Götaland, Sahlgrenska University Hospital, 41345 Gothenburg, Sweden
| | - Louise E Olofsson
- Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, 41345 Gothenburg, Sweden.
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36
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Schalla MA, Taché Y, Stengel A. Neuroendocrine Peptides of the Gut and Their Role in the Regulation of Food Intake. Compr Physiol 2021; 11:1679-1730. [PMID: 33792904 DOI: 10.1002/cphy.c200007] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The regulation of food intake encompasses complex interplays between the gut and the brain. Among them, the gastrointestinal tract releases different peptides that communicate the metabolic state to specific nuclei in the hindbrain and the hypothalamus. The present overview gives emphasis on seven peptides that are produced by and secreted from specialized enteroendocrine cells along the gastrointestinal tract in relation with the nutritional status. These established modulators of feeding are ghrelin and nesfatin-1 secreted from gastric X/A-like cells, cholecystokinin (CCK) secreted from duodenal I-cells, glucagon-like peptide 1 (GLP-1), oxyntomodulin, and peptide YY (PYY) secreted from intestinal L-cells and uroguanylin (UGN) released from enterochromaffin (EC) cells. © 2021 American Physiological Society. Compr Physiol 11:1679-1730, 2021.
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Affiliation(s)
- Martha A Schalla
- Charité Center for Internal Medicine and Dermatology, Department for Psychosomatic Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
| | - Yvette Taché
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, CURE: Digestive Diseases Research Center, David Geffen School of Medicine, UCLA, Los Angeles, California, USA.,VA Greater Los Angeles Healthcare System, Los Angeles, California, USA
| | - Andreas Stengel
- Charité Center for Internal Medicine and Dermatology, Department for Psychosomatic Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany.,Department of Psychosomatic Medicine and Psychotherapy, Medical University Hospital Tübingen, Tübingen, Germany
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37
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Lee CY. A Combination of Glucagon-Like Peptide-1 Receptor Agonist and Dietary Intervention Could Be a Promising Approach for Obesity Treatment. Front Endocrinol (Lausanne) 2021; 12:748477. [PMID: 34616367 PMCID: PMC8489573 DOI: 10.3389/fendo.2021.748477] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Accepted: 08/30/2021] [Indexed: 12/14/2022] Open
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Pereira SC, Crisóstomo L, Sousa M, Oliveira PF, Alves MG. Metabolic diseases affect male reproduction and induce signatures in gametes that may compromise the offspring health. ENVIRONMENTAL EPIGENETICS 2020; 6:dvaa019. [PMID: 33324496 PMCID: PMC7722800 DOI: 10.1093/eep/dvaa019] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Revised: 09/03/2020] [Accepted: 09/15/2020] [Indexed: 05/30/2023]
Abstract
The most prevalent diseases worldwide are non-communicable such as obesity and type 2 diabetes. Noteworthy, the prevalence of obesity and type 2 diabetes is expected to steadily increase in the next decades, mostly fueled by bad feeding habits, stress, and sedentarism. The reproductive function of individuals is severely affected by abnormal metabolic environments, both at mechanical and biochemical levels. Along with mechanical dysfunctions, and decreased sperm quality (promoted both directly and indirectly by metabolic abnormalities), several studies have already reported the potentially harmful effects of metabolic disorders in the genetic and epigenetic cargo of spermatozoa, and the epigenetic inheritance of molecular signatures induced by metabolic profile (paternal diet, obesity, and diabetes). The inheritance of epigenetic factors towards the development of metabolic abnormalities means that more people in reproductive age can potentially suffer from these disorders and for longer periods. In its turn, these individuals can also transmit this (epi)genetic information to future generations, creating a vicious cycle. In this review, we collect the reported harmful effects related to acquired metabolic disorders and diet in sperm parameters and male reproductive potential. Besides, we will discuss the novel findings regarding paternal epigenetic inheritance, particularly the ones induced by paternal diet rich in fats, obesity, and type 2 diabetes. We analyze the data attained with in vitro and animal models as well as in long-term transgenerational population studies. Although the findings on this topic are very recent, epigenetic inheritance of metabolic disease has a huge societal impact, which may be crucial to tackle the 'fat epidemic' efficiently.
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Affiliation(s)
- Sara C Pereira
- Unit for Multidisciplinary Research in Biomedicine (UMIB), Laboratory of Cell Biology, Department of Microscopy, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal
| | - Luís Crisóstomo
- Unit for Multidisciplinary Research in Biomedicine (UMIB), Laboratory of Cell Biology, Department of Microscopy, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal
| | - Mário Sousa
- Unit for Multidisciplinary Research in Biomedicine (UMIB), Laboratory of Cell Biology, Department of Microscopy, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal
| | - Pedro F Oliveira
- QOPNA & LAQV, Department of Chemistry, University of Aveiro, Aveiro, Portugal
| | - Marco G Alves
- Unit for Multidisciplinary Research in Biomedicine (UMIB), Laboratory of Cell Biology, Department of Microscopy, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal
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Diz-Chaves Y, Herrera-Pérez S, González-Matías LC, Lamas JA, Mallo F. Glucagon-Like Peptide-1 (GLP-1) in the Integration of Neural and Endocrine Responses to Stress. Nutrients 2020; 12:nu12113304. [PMID: 33126672 PMCID: PMC7692797 DOI: 10.3390/nu12113304] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Revised: 10/14/2020] [Accepted: 10/27/2020] [Indexed: 12/20/2022] Open
Abstract
Glucagon like-peptide 1 (GLP-1) within the brain is produced by a population of preproglucagon neurons located in the caudal nucleus of the solitary tract. These neurons project to the hypothalamus and another forebrain, hindbrain, and mesolimbic brain areas control the autonomic function, feeding, and the motivation to feed or regulate the stress response and the hypothalamic-pituitary-adrenal axis. GLP-1 receptor (GLP-1R) controls both food intake and feeding behavior (hunger-driven feeding, the hedonic value of food, and food motivation). The activation of GLP-1 receptors involves second messenger pathways and ionic events in the autonomic nervous system, which are very relevant to explain the essential central actions of GLP-1 as neuromodulator coordinating food intake in response to a physiological and stress-related stimulus to maintain homeostasis. Alterations in GLP-1 signaling associated with obesity or chronic stress induce the dysregulation of eating behavior. This review summarized the experimental shreds of evidence from studies using GLP-1R agonists to describe the neural and endocrine integration of stress responses and feeding behavior.
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Affiliation(s)
- Yolanda Diz-Chaves
- CINBIO, Universidade de Vigo, Grupo FB3A, Laboratorio de Endocrinología, 36310 Vigo, Spain;
- Correspondence: (Y.D.-C.); (F.M.); Tel.: +34-(986)-130226 (Y.D.-C.); +34-(986)-812393 (F.M.)
| | - Salvador Herrera-Pérez
- CINBIO, Universidade de Vigo, Grupo FB3B, Laboratorio de Neurociencia, 36310 Vigo, Spain; (S.H.-P.); (J.A.L.)
| | | | - José Antonio Lamas
- CINBIO, Universidade de Vigo, Grupo FB3B, Laboratorio de Neurociencia, 36310 Vigo, Spain; (S.H.-P.); (J.A.L.)
| | - Federico Mallo
- CINBIO, Universidade de Vigo, Grupo FB3A, Laboratorio de Endocrinología, 36310 Vigo, Spain;
- Correspondence: (Y.D.-C.); (F.M.); Tel.: +34-(986)-130226 (Y.D.-C.); +34-(986)-812393 (F.M.)
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40
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Braga TG, Graças Coelho de Souza MD, Menezes M, Nogueira Neto JF, Dellatorre-Teixeira L, Bouskela E, le Roux CW, Kraemer-Aguiar LG. Dipeptidyl peptidase-4 activity, lipopolysaccharide, C-reactive protein, glucose metabolism, and gut peptides 3 months after bariatric surgery. Surg Obes Relat Dis 2020; 17:113-120. [PMID: 33036944 DOI: 10.1016/j.soard.2020.08.030] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Revised: 08/17/2020] [Accepted: 08/19/2020] [Indexed: 01/06/2023]
Abstract
BACKGROUND Bariatric surgery induces weight loss, but changes in glucose metabolism, gut peptides, and inflammatory biomarkers still have conflicting results. SETTINGS University hospital. OBJECTIVES We investigated glucose metabolism, gut hormones, and inflammatory profile after bariatric surgery and medical treatment. METHODS Forty patients with obesity were recruited and were subjected to Roux-en-Y gastric bypass (n = 15; Bariatric Surgery Group - BSG) or received medical care (n = 20; MG). Sleeve gastrectomy was performed in five patients who were excluded from analysis. Glucose, insulin, homeostatic model for the assessment of insulin resistance (HOMA-IR), glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), glucagon, ghrelin, dipeptidyl peptidase-4 (DPP-4) activity, circulating lipopolysaccharide (LPS), LPS-binding protein (LPB) and high-sensitivity C-reactive protein (hs-CRP) were evaluated before and three months after each treatment. Except for HOMA-IR, hs-CRP, and LBP, all variables were assessed at fasting and 30- and 60-minutes after a standard meal. RESULTS After 3 months, both groups lost weight. However, BSG had a more extensive reduction than MG (respectively, 17.6% vs. 4.25%; P < 0.01). Except for LPS levels, higher on BSG than MG (1.38 ± 0.96 vs. 0.83 ± 0.60 EU/ml, P < 0.01), groups were similar before treatment. In respect to metabolic/hormonal changes, the BSG showed higher glucose, insulin, GLP-1, and GIP levels at 30-min and also GLP-1 at 30- and 60-minutes. DPP-4 activity, HOMA-IR, and fasting LBP did not change. LPS levels at 60-minutes decreased after surgery in the BSG. hs-CRP decreased on BSG compared to MG. CONCLUSIONS Bariatric surgery resulted in more extensive effects on glucose metabolism, gut hormones, and inflammation.
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Affiliation(s)
- Tassia Gomide Braga
- Postgraduate Program in Clinical and Experimental Physiopathology, Faculty of Medical Sciences, State University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Maria Das Graças Coelho de Souza
- Laboratory of Clinical and Experimental Research on Vascular Biology, Biomedical Center, State University of Rio de Janeiro, Rio de Janeiro, Brazil
| | | | | | | | - Eliete Bouskela
- Laboratory of Clinical and Experimental Research on Vascular Biology, Biomedical Center, State University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Carel W le Roux
- Diabetes Complications Research Centre Conway Institute University College, Dublin, Ireland; Investigate Science, Imperial College, London, United Kingdom
| | - Luiz Guilherme Kraemer-Aguiar
- Laboratory of Clinical and Experimental Research on Vascular Biology, Biomedical Center, State University of Rio de Janeiro, Rio de Janeiro, Brazil; Obesity Unit, Department of Internal Medicine, Faculty of Medical Sciences, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
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41
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Wueest S, Konrad D. The controversial role of IL-6 in adipose tissue on obesity-induced dysregulation of glucose metabolism. Am J Physiol Endocrinol Metab 2020; 319:E607-E613. [PMID: 32715746 DOI: 10.1152/ajpendo.00306.2020] [Citation(s) in RCA: 50] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Interleukin (IL)-6 is a pleotropic cytokine with various physiological and pathophysiological functions in different cells and tissues. In cells residing within white adipose tissue, several, and sometimes conflicting, IL-6 actions have been described in the development of obesity-associated derangements of glucose metabolism. Herein, we aim to summarize opposing findings and discuss recent evidence that IL-6 signaling in adipose tissue is regulated in a depot and cell-specific manner.
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Affiliation(s)
- Stephan Wueest
- Division of Pediatric Endocrinology and Diabetology, University Children's Hospital, Zurich, Switzerland
- Children's Research Center, University Children's Hospital, Zurich, Switzerland
| | - Daniel Konrad
- Division of Pediatric Endocrinology and Diabetology, University Children's Hospital, Zurich, Switzerland
- Children's Research Center, University Children's Hospital, Zurich, Switzerland
- Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
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42
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Tian L, Ning H, Shao W, Song Z, Badakhshi Y, Ling W, Yang BB, Brubaker PL, Jin T. Dietary Cyanidin-3-Glucoside Attenuates High-Fat-Diet-Induced Body-Weight Gain and Impairment of Glucose Tolerance in Mice via Effects on the Hepatic Hormone FGF21. J Nutr 2020; 150:2101-2111. [PMID: 32470979 PMCID: PMC7398791 DOI: 10.1093/jn/nxaa140] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Revised: 01/08/2020] [Accepted: 04/27/2020] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND Dietary polyphenols including anthocyanins target multiple organs. OBJECTIVE We aimed to assess the involvement of glucagon-like peptide 1 (GLP-1), leptin, insulin and fibroblast growth factor 21 (FGF21) in mediating metabolic beneficial effects of purified anthocyanin cyanidin-3-glucoside (Cy3G). METHODS Intestinal proglucagon gene (Gcg; encoding GLP-1) and liver Fgf21 expression were assessed in 6-wk-old male C57BL-6J mice fed a low-fat-diet (LFD; 10% of energy from fat), alone or with 1.6 mg Cy3G/L in drinking water for 3 wk [experiment (Exp.) 1; n = 5/group]. Similar mice were fed the LFD or a high-fat diet (HFD; 60% energy from fat) with or without Cy3G for 20 wk. Half of the mice administered Cy3G also received 4 broad-spectrum antibiotics (ABs) in drinking water between weeks 11 and 14, for a total of 6 groups (n = 8/group). Metabolic tolerance tests were conducted between weeks 2 and 16. Relevant hormone gene expression and plasma hormone concentrations were assessed mainly at the end of 20 wk (Exp. 2). RESULTS In Exp. 1, Cy3G administration increased ileal but not colonic Gcg level by 2-fold (P < 0.05). In Exp. 2, Cy3G attenuated HFD-induced body-weight gain (20.3% at week 16), and improved glucose tolerance (26.5% at week 15) but not insulin tolerance. Although Cy3G had no effect on glucose tolerance in LFD mice, LFD/Cy3G/AB mice showed better glucose tolerance than LFD/Cy3G mice (23%). In contrast, HFD/Cy3G/AB mice showed worse glucose tolerance compared with HFD/Cy3G mice (15%). Beneficial effects of Cy3G in HFD mice were not associated with changes in plasma leptin, insulin or GLP-1 concentrations. However, Cy3G increased hepatic Fgf21 expression in mice in Exp. 1 by 4-fold and attenuated Fgf21 overexpression in HFD mice (Exp. 2, 22%), associated with increased expression of genes that encode FGFR1 and β-klotho (>3-fold, P < 0.05). CONCLUSIONS Dietary Cy3G may reduce body weight and exert metabolic homeostatic effects in mice via changes in hepatic FGF21.
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Affiliation(s)
- Lili Tian
- Division of Advanced Diagnostics, Toronto General Hospital Research Institute, University Health Network, Toronto, Canada,Department of Physiology, University of Toronto, Toronto, Canada,Banting and Best Diabetes Centre, Faculty of Medicine, University of Toronto, Toronto, Canada
| | - Hongmei Ning
- Division of Advanced Diagnostics, Toronto General Hospital Research Institute, University Health Network, Toronto, Canada,Henan Institute of Science and Technology, Xinxiang, Henan, China
| | - Weijuan Shao
- Division of Advanced Diagnostics, Toronto General Hospital Research Institute, University Health Network, Toronto, Canada,Department of Physiology, University of Toronto, Toronto, Canada,Banting and Best Diabetes Centre, Faculty of Medicine, University of Toronto, Toronto, Canada
| | - Zhuolun Song
- Division of Advanced Diagnostics, Toronto General Hospital Research Institute, University Health Network, Toronto, Canada,Department of Physiology, University of Toronto, Toronto, Canada,Banting and Best Diabetes Centre, Faculty of Medicine, University of Toronto, Toronto, Canada
| | - Yasaman Badakhshi
- Division of Advanced Diagnostics, Toronto General Hospital Research Institute, University Health Network, Toronto, Canada,Department of Physiology, University of Toronto, Toronto, Canada,Banting and Best Diabetes Centre, Faculty of Medicine, University of Toronto, Toronto, Canada
| | - Wenhua Ling
- Department of Nutrition, School of Public Health, Sun Yet-Sen University, Guangzhou, China
| | - Burton B Yang
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada
| | - Patricia L Brubaker
- Department of Physiology, University of Toronto, Toronto, Canada,Department of Medicine, University of Toronto, Toronto, Canada
| | - Tianru Jin
- Division of Advanced Diagnostics, Toronto General Hospital Research Institute, University Health Network, Toronto, Canada,Department of Physiology, University of Toronto, Toronto, Canada,Banting and Best Diabetes Centre, Faculty of Medicine, University of Toronto, Toronto, Canada,Department of Medicine, University of Toronto, Toronto, Canada,Address correspondence to TJ (e-mail: )
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Campbell JR, Martchenko A, Sweeney ME, Maalouf MF, Psichas A, Gribble FM, Reimann F, Brubaker PL. Essential Role of Syntaxin-Binding Protein-1 in the Regulation of Glucagon-Like Peptide-1 Secretion. Endocrinology 2020; 161:5788420. [PMID: 32141504 PMCID: PMC7124137 DOI: 10.1210/endocr/bqaa039] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Accepted: 02/28/2020] [Indexed: 12/12/2022]
Abstract
Circadian secretion of the incretin, glucagon-like peptide-1 (GLP-1), correlates with expression of the core clock gene, Bmal1, in the intestinal L-cell. Several SNARE proteins known to be circadian in pancreatic α- and β-cells are also necessary for GLP-1 secretion. However, the role of the accessory SNARE, Syntaxin binding protein-1 (Stxbp1; also known as Munc18-1) in the L-cell is unknown. The aim of this study was to determine whether Stxbp1 is under circadian regulation in the L-cell and its role in the control of GLP-1 secretion. Stxbp1 was highly-enriched in L-cells, and STXBP1 was expressed in a subpopulation of L-cells in mouse and human intestinal sections. Stxbp1 transcripts and protein displayed circadian patterns in mGLUTag L-cells line, while chromatin-immunoprecipitation revealed increased interaction between BMAL1 and Stxbp1 at the peak time-point of the circadian pattern. STXBP1 recruitment to the cytosol and plasma membrane within 30 minutes of L-cell stimulation was also observed at this time-point. Loss of Stxbp1 in vitro and in vivo led to reduced stimulated GLP-1 secretion at the peak time-point of circadian release, and impaired GLP-1 secretion ex vivo. In conclusion, Stxbp1 is a circadian regulated exocytotic protein in the intestinal L-cell that is an essential regulatory component of GLP-1 secretion.
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Affiliation(s)
| | | | - Maegan E Sweeney
- Departments of Physiology, University of Toronto, Toronto, ON, Canada
| | - Michael F Maalouf
- Departments of Physiology, University of Toronto, Toronto, ON, Canada
| | - Arianna Psichas
- Departments of Medicine, University of Toronto, Toronto, ON, Canada
| | - Fiona M Gribble
- Departments of Medicine, University of Toronto, Toronto, ON, Canada
| | - Frank Reimann
- Departments of Medicine, University of Toronto, Toronto, ON, Canada
| | - Patricia L Brubaker
- Departments of Physiology, University of Toronto, Toronto, ON, Canada
- Wellcome Trust-MRC Institute of Metabolic Science – Metabolic Research Laboratories (IMS-MRL), University of Cambridge, Cambridge, UK
- Correspondence: P.L. Brubaker, Rm. 3366 Medical Sciences Building, University of Toronto, 1 King’s College Circle, Toronto, ON M5S 1A8. E-mail:
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Sun C, Qian Y, Liu W, Xu W, Wang K, Liu B. Dietary squid paste supplementation promotes feed intake via brain-gut dynamic response in Chinese soft-shelled turtle Pelodiscus sinensis. PeerJ 2020; 8:e9031. [PMID: 32355579 PMCID: PMC7185028 DOI: 10.7717/peerj.9031] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2019] [Accepted: 03/31/2020] [Indexed: 01/26/2023] Open
Abstract
Background As the primary source of protein for aquaculture, fishmeal has reached the extremity of sustainable development, our previous studies have proven that rice protein concentrate and squid paste are outstanding protein source and stimulant for Pelodiscus sinensis. However, little attention has been given to the molecular mechanism of the appetite modulated by the dietary nutrient factor, especially for a reptile. Thus, the present study aimed to evaluate feed intake and brain-gut dynamic responses to dietary rice protein concentrate and squid paste in Chinese soft-shelled turtle Pelodiscus sinensis. Methods Three isonitrogenous and isoenergetic practical diets were formulated including 60% fishmeal (CT), 42% fishmeal + 18% rice protein concentrate (RP) and 42% fishmeal + 18% rice protein concentrate + 1% squid paste (RPS), respectively. Microcapsule lysine was supplemented in RP and RPS diets to balance the amino acid profile. Turtles (initial weight 30.65 ± 0.97 g) were fed three times daily to apparent satiation. After the 8-week feeding trial, the turtles were exposed to 48h food deprivation, then the dynamic expression of the orexigenic and anorexigenic peptides were measured. Results The results showed that no significant effect was observed on feed intake when fishmeal was replaced by rice protein concentrate (P = 0.421), while significantly improved feed intake was found by squid paste supplemented (P = 0.02). The mRNA expression of anorexigenic peptides, such as leptin receptor, insulin receptor, pro-opiomelanocortin, cocaine and amphetamine-regulated transcript, cholecystokinin (and its receptor) and glucagon-like peptide-1 receptor in the brain increased significantly at 3 h past feeding (P < 0.05), and then decreased. Nevertheless, neuropeptide Y and peptide YY mRNA expression showed the valley at 3h and peak at 12h past feeding. Intestinal cholecystokinin receptor and glucagon-like peptide-1 receptor mRNA expression showed no difference during the postprandial time (P > 0.05). The results suggested that squid paste is an outstanding stimulant for Pelodiscus sinensis. Furthermore, the orexigenic and anorexigenic peptides evaluated here might play an essential role in short-term fasting to this species, of which the dynamic expression levels were regulated by squid paste.
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Affiliation(s)
- Cunxin Sun
- Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture and Rural Affairs, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi, China.,Laboratory of Aquatic Nutrition and Ecology, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China
| | - Yu Qian
- Laboratory of Aquatic Nutrition and Ecology, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China
| | - Wenbin Liu
- Laboratory of Aquatic Nutrition and Ecology, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China
| | - Weina Xu
- Laboratory of Aquatic Nutrition and Ecology, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.,School of Agriculture and Biology, Shanghai Jiaotong University, Shanghai, China
| | - Kaizhou Wang
- Laboratory of Aquatic Nutrition and Ecology, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China
| | - Bo Liu
- Key Laboratory of Freshwater Fisheries and Germplasm Resources Utilization, Ministry of Agriculture and Rural Affairs, Freshwater Fisheries Research Center, Chinese Academy of Fishery Sciences, Wuxi, China
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Higgins V, Asgari S, Hamilton JK, Wolska A, Remaley AT, Hartmann B, Holst JJ, Adeli K. Postprandial Dyslipidemia, Hyperinsulinemia, and Impaired Gut Peptides/Bile Acids in Adolescents with Obesity. J Clin Endocrinol Metab 2020; 105:dgz261. [PMID: 31825485 PMCID: PMC7065844 DOI: 10.1210/clinem/dgz261] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Accepted: 12/10/2019] [Indexed: 01/08/2023]
Abstract
BACKGROUND With increased rates of obesity and insulin resistance in youth, development of postprandial dyslipidemia, an important cardiovascular disease risk factor, is a concern. Glucagon-like peptides (ie, GLP-1 and GLP-2) and bile acids have been shown to regulate dietary fat absorption and postprandial lipids in animal models and humans. We hypothesize that the physiological response of GLPs and bile acids to dietary fat ingestion is impaired in adolescents with obesity and this associates with marked postprandial dyslipidemia and insulin resistance. METHODS In this cross-sectional study, normal weight adolescents and adolescents with obesity underwent a 6-hour oral fat tolerance test. The postprandial lipoprotein phenotype profile was determined using various assays, including nuclear magnetic resonance spectroscopy, to characterize lipoprotein particle number, size, lipid content, and apolipoproteins. GLP-1 and GLP-2 were quantified by electrochemiluminescent immunoassays. Total bile acids were measured by an automated enzymatic cycling colorimetric method and the bile acid profile by mass spectrometry. RESULTS Adolescents with obesity exhibited fasting and postprandial dyslipidemia, particularly augmented postprandial excursion of large triglyceride-rich lipoproteins. Postprandial GLPs were reduced and inversely correlated with postprandial dyslipidemia and insulin resistance. Postprandial bile acids were also diminished, particularly lithocholic acid, a potent stimulator of GLP-1 secretion. CONCLUSION Blunted postprandial GLP and bile acid response to dietary fat ingestion strongly associates with marked postprandial dyslipidemia. Further investigation is needed to assess their potential utility as early biomarkers for postprandial dyslipidemia in adolescents with obesity.
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Affiliation(s)
- Victoria Higgins
- Molecular Medicine and Pediatric Laboratory Medicine, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada
- Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada
| | - Shervin Asgari
- Molecular Medicine and Pediatric Laboratory Medicine, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada
| | - Jill K Hamilton
- Division of Endocrinology, The Hospital for Sick Children, Toronto, ON, Canada
- Department of Paediatrics, University of Toronto, Toronto, ON, Canada
| | - Anna Wolska
- National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland
| | - Alan T Remaley
- National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland
| | - Bolette Hartmann
- Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
| | - Jens J Holst
- Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
| | - Khosrow Adeli
- Molecular Medicine and Pediatric Laboratory Medicine, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada
- Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada
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Handgraaf S, Dusaulcy R, Visentin F, Philippe J, Gosmain Y. Let-7e-5p Regulates GLP-1 Content and Basal Release From Enteroendocrine L Cells From DIO Male Mice. Endocrinology 2020; 161:5697307. [PMID: 31905402 DOI: 10.1210/endocr/bqz037] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2019] [Accepted: 01/02/2020] [Indexed: 12/30/2022]
Abstract
Characterization of enteroendocrine L cells in diabetes is critical for better understanding of the role of glucagon-like peptide-1 (GLP-1) in physiology and diabetes. We studied L-cell transcriptome changes including microRNA (miRNA) dysregulation in obesity and diabetes. We evaluated the regulation of miRNAs through microarray analyses on sorted enteroendocrine L cells from control and obese glucose-intolerant (I-HFD) and hyperglycemic (H-HFD) mice after 16 weeks of respectively low-fat diet (LFD) or high-fat diet (HFD) feeding. The identified altered miRNAs were studied in vitro using the mouse GLUTag cell line to investigate their regulation and potential biological functions. We identified that let-7e-5p, miR-126a-3p, and miR-125a-5p were differentially regulated in L cells of obese HFD mice compared with control LFD mice. While downregulation of let-7e-5p expression was observed in both I-HFD and H-HFD mice, levels of miR-126a-3p increased and of miR-125a-5p decreased significantly only in I-HFD mice compared with controls. Using miRNA inhibitors and mimics we observed that modulation of let-7e-5p expression affected specifically GLP-1 cellular content and basal release, whereas Gcg gene expression and acute GLP-1 secretion and cell proliferation were not affected. In addition, palmitate treatment resulted in a decrease of let-7e-5p expression along with an increase in GLP-1 content and release, suggesting that palmitate acts on GLP-1 through let-7e-5p. By contrast, modulation of miR-125a-5p and miR-126a-3p in the same conditions did not affect content or secretion of GLP-1. We conclude that decrease of let-7e-5p expression in response to palmitate may constitute a compensatory mechanism contributing to maintaining constant glycemia in obese mice.
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Affiliation(s)
- Sandra Handgraaf
- Molecular Diabetes Laboratory, Division of Endocrinology, Diabetes, Hypertension and Nutrition, University Hospital/Diabetes Center/University of Geneva Medical School, Geneva, Switzerland
| | - Rodolphe Dusaulcy
- Molecular Diabetes Laboratory, Division of Endocrinology, Diabetes, Hypertension and Nutrition, University Hospital/Diabetes Center/University of Geneva Medical School, Geneva, Switzerland
| | - Florian Visentin
- Molecular Diabetes Laboratory, Division of Endocrinology, Diabetes, Hypertension and Nutrition, University Hospital/Diabetes Center/University of Geneva Medical School, Geneva, Switzerland
| | - Jacques Philippe
- Molecular Diabetes Laboratory, Division of Endocrinology, Diabetes, Hypertension and Nutrition, University Hospital/Diabetes Center/University of Geneva Medical School, Geneva, Switzerland
| | - Yvan Gosmain
- Molecular Diabetes Laboratory, Division of Endocrinology, Diabetes, Hypertension and Nutrition, University Hospital/Diabetes Center/University of Geneva Medical School, Geneva, Switzerland
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Vanderhout SM, Aglipay M, Torabi N, Jüni P, da Costa BR, Birken CS, O'Connor DL, Thorpe KE, Maguire JL. Whole milk compared with reduced-fat milk and childhood overweight: a systematic review and meta-analysis. Am J Clin Nutr 2020; 111:266-279. [PMID: 31851302 PMCID: PMC6997094 DOI: 10.1093/ajcn/nqz276] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2019] [Accepted: 10/14/2019] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND The majority of children in North America consume cow-milk daily. Children aged >2 y are recommended to consume reduced-fat (0.1-2%) cow-milk to lower the risk of obesity. OBJECTIVES To evaluate the relation between cow-milk fat consumption and adiposity in children aged 1-18 y. METHODS Embase (Excerpta Medica Database), CINAHL (Cumulative Index to Nursing and Allied Health Literature), MEDLINE, Scopus, and Cochrane Library databases from inception to August 2019 were used. The search included observational and interventional studies of healthy children aged 1-18 y that described the association between cow-milk fat consumption and adiposity. Two reviewers extracted data, using the Newcastle-Ottawa Scale to assess risk of bias. Meta-analysis was conducted using random effects to evaluate the relation between cow-milk fat and risk of overweight or obesity. Adiposity was assessed using BMI z-score (zBMI). RESULTS Of 5862 reports identified by the search, 28 met the inclusion criteria: 20 were cross-sectional and 8 were prospective cohort. No clinical trials were identified. In 18 studies, higher cow-milk fat consumption was associated with lower child adiposity, and 10 studies did not identify an association. Meta-analysis included 14 of the 28 studies (n = 20,897) that measured the proportion of children who consumed whole milk compared with reduced-fat milk and direct measures of overweight or obesity. Among children who consumed whole (3.25% fat) compared with reduced-fat (0.1-2%) milk, the OR of overweight or obesity was 0.61 (95% CI: 0.52, 0.72; P < 0.0001), but heterogeneity between studies was high (I2 = 73.8%). CONCLUSIONS Observational research suggests that higher cow-milk fat intake is associated with lower childhood adiposity. International guidelines that recommend reduced-fat milk for children might not lower the risk of childhood obesity. Randomized trials are needed to determine which cow-milk fat minimizes risk of excess adiposity. This systematic review and meta-analysis was registered with PROSPERO (registration number: CRD42018085075).
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Affiliation(s)
- Shelley M Vanderhout
- Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada,Department of Paediatrics, St Michael's Hospital, Toronto, Ontario, Canada,Applied Health Research Centre, St Michael's Hospital, Toronto, Ontario, Canada
| | - Mary Aglipay
- Department of Paediatrics, St Michael's Hospital, Toronto, Ontario, Canada
| | - Nazi Torabi
- Scotiabank Health Sciences Library, Li Ka Shing Knowledge Institute of St Michael's Hospital, Toronto, Ontario, Canada
| | - Peter Jüni
- Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada,Applied Health Research Centre, St Michael's Hospital, Toronto, Ontario, Canada
| | - Bruno R da Costa
- Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada,Applied Health Research Centre, St Michael's Hospital, Toronto, Ontario, Canada
| | - Catherine S Birken
- Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada,Division of Paediatric Medicine and the Paediatric Outcomes Research Team, The Hospital for Sick Children, Toronto, Ontario, Canada,Child Health Evaluative Sciences, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Deborah L O'Connor
- Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada,Child Health Evaluative Sciences, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Kevin E Thorpe
- Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada,Applied Health Research Centre, St Michael's Hospital, Toronto, Ontario, Canada
| | - Jonathon L Maguire
- Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada,Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada,Department of Paediatrics, St Michael's Hospital, Toronto, Ontario, Canada,Applied Health Research Centre, St Michael's Hospital, Toronto, Ontario, Canada,Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada,Division of Paediatric Medicine and the Paediatric Outcomes Research Team, The Hospital for Sick Children, Toronto, Ontario, Canada,Child Health Evaluative Sciences, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, Ontario, Canada,Address correspondence to JLM (e-mail: )
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Hira T, Pinyo J, Hara H. What Is GLP-1 Really Doing in Obesity? Trends Endocrinol Metab 2020; 31:71-80. [PMID: 31636017 DOI: 10.1016/j.tem.2019.09.003] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2019] [Revised: 08/28/2019] [Accepted: 09/10/2019] [Indexed: 02/06/2023]
Abstract
Glucagon-like peptide-1 (GLP-1) is a gastrointestinal hormone released in response to meal ingestion and enhances insulin secretion from pancreatic β cells. In several human studies, GLP-1 secretory responses to oral glucose load or a meal were decreased in subjects with obesity, glucose intolerance, or diabetes compared with those in healthy subjects. However, the results of meta-analysis and cohort studies do not necessarily support this concept. Results from animal studies are also inconsistent; in multiple studies, GLP-1 secretory responses to a meal were repeatedly higher in diet-induced obese rats than in control rats. Thus, the postprandial GLP-1 response is not necessarily decreased but rather enhanced during obesity development, which is likely to play a protective role against glucose intolerance.
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Affiliation(s)
- Tohru Hira
- Research Faculty of Agriculture, Hokkaido University, Sapporo, Japan; Graduate School of Agriculture, Hokkaido University, Sapporo, Japan.
| | - Jukkrapong Pinyo
- Graduate School of Agriculture, Hokkaido University, Sapporo, Japan
| | - Hiroshi Hara
- Department of Food Science and Human Nutrition, Fuji Women's University, Ishikari, Hokkaido, Japan
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Stahel P, Xiao C, Nahmias A, Lewis GF. Role of the Gut in Diabetic Dyslipidemia. Front Endocrinol (Lausanne) 2020; 11:116. [PMID: 32231641 PMCID: PMC7083132 DOI: 10.3389/fendo.2020.00116] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2019] [Accepted: 02/21/2020] [Indexed: 12/13/2022] Open
Abstract
Type 2 diabetes (T2D) is associated with increased risk of cardiovascular disease (CVD). In insulin resistant states such as the metabolic syndrome, overproduction and impaired clearance of liver-derived very-low-density lipoproteins and gut-derived chylomicrons (CMs) contribute to hypertriglyceridemia and elevated atherogenic remnant lipoproteins. Although ingested fat is the major stimulus of CM secretion, intestinal lipid handling and ultimately CM secretory rate is determined by numerous additional regulatory inputs including nutrients, hormones and neural signals that fine tune CM secretion during fasted and fed states. Insulin resistance and T2D represent perturbed metabolic states in which intestinal sensitivity to key regulatory hormones such as insulin, leptin and glucagon-like peptide-1 (GLP-1) may be altered, contributing to increased CM secretion. In this review, we describe the evidence from human and animal models demonstrating increased CM secretion in insulin resistance and T2D and discuss the molecular mechanisms underlying these effects. Several novel compounds are in various stages of preclinical and clinical investigation to modulate intestinal CM synthesis and secretion. Their efficacy, safety and therapeutic utility are discussed. Similarly, the effects of currently approved lipid modulating therapies such as statins, ezetimibe, fibrates, and PCSK9 inhibitors on intestinal CM production are discussed. The intricacies of intestinal CM production are an active area of research that may yield novel therapies to prevent atherosclerotic CVD in insulin resistance and T2D.
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Yang K, Zhang X, Zhou Y, Chen F, Shen M, Wang Y. Changes in Serum Nesfatin-1 After Laparoscopic Sleeve Gastrectomy are Associated with Improvements in Nonalcoholic Fatty Liver Disease. Diabetes Metab Syndr Obes 2020; 13:1459-1464. [PMID: 32431529 PMCID: PMC7200260 DOI: 10.2147/dmso.s246281] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Accepted: 03/15/2020] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a serious and widespread disease worldwide. Bariatric surgery is one of the treatments for NAFLD. Nesfatin-1 is located in the brain, periphery and plasma. We studied the relationship between nesfatin-1 changes after laparoscopic sleeve gastrectomy (LSG) and NAFLD remission. METHODS A total of 29 patients participated in the study, which collected clinical information on the patients and indicators of liver function, hepatic steatosis score and nesfatin-1 level before and after LSG. RESULTS The average BMI of the patients before surgery was 42.63±8.91 kg/m2, and the average BMI was 28.54±5.63 kg/m2 one year after surgery (p < 0.05). One year after LSG, the total weight loss percentage (TWL%) was 32.11±7.10%. The mean value of nesfatin-1 before surgery was 3.04±0.81 ng/mL, and the mean value of nesfatin-1 was 5.52±1.55 ng/mL at one year after surgery (p < 0.05). The average preoperative hepatic steatosis index (HSI) score of the patients was 52.55±9.17, and the average postoperative HSI score was 38.84±5.82 (p < 0.05). Before LSG (p < 0.05, r= -0.81) and 1 year after surgery (p < 0.05, r = -0.58), HSI and nesfatin-1 were significantly negatively correlated. Percentage of increased nesfatin-1 and percentage of decreased HSI showed positive correlation after LSG. CONCLUSION There was a negative correlation between HSI and nesfatin-1 before and after LSG, which may suggest that nesfatin-1 plays a role in NAFLD.
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Affiliation(s)
- Keyu Yang
- Department of General Surgery, Fourth Affiliated Hospital of China Medical University, Shenyang City, Liaoning Province110032, People’s Republic of China
| | - Xiaowei Zhang
- Department of General Surgery, Fourth Affiliated Hospital of China Medical University, Shenyang City, Liaoning Province110032, People’s Republic of China
| | - Yong Zhou
- Department of General Surgery, Fourth Affiliated Hospital of China Medical University, Shenyang City, Liaoning Province110032, People’s Republic of China
| | - Fu Chen
- Department of General Surgery, Fourth Affiliated Hospital of China Medical University, Shenyang City, Liaoning Province110032, People’s Republic of China
| | - Mingyang Shen
- Department of General Surgery, Fourth Affiliated Hospital of China Medical University, Shenyang City, Liaoning Province110032, People’s Republic of China
| | - Yong Wang
- Department of General Surgery, Fourth Affiliated Hospital of China Medical University, Shenyang City, Liaoning Province110032, People’s Republic of China
- Correspondence: Yong Wang Department of General Surgery, Fourth Affiliated Hospital of China Medical University, No. 4, Chongshan East Road, Huanggu District, Shenyang City, Liaoning Province110032, People’s Republic of ChinaTel +8618940259733 Email
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