International Journal of Molecular Sciences

Research

Jump to: Review

17 pages, 10807 KiB

Open AccessArticle

Biological Determinants of Metabolic Syndrome in Visceral and Subcutaneous Adipose Tissue from Severely Obese Women

by Óscar Osorio-Conles, Arturo Vega-Beyhart, Ainitze Ibarzabal, José María Balibrea, Josep Vidal and Ana de Hollanda

Int. J. Mol. Sci. 2022, 23(4), 2394; https://doi.org/10.3390/ijms23042394 - 21 Feb 2022

Cited by 1 | Viewed by 3388

Abstract

The metabolic syndrome (MetS) is a cluster of the most dangerous heart attack risk factors: diabetes or raised fasting plasma glucose, abdominal obesity, high cholesterol and high blood pressure. The goal of this study is to compare the state of the main features [...] Read more.

The metabolic syndrome (MetS) is a cluster of the most dangerous heart attack risk factors: diabetes or raised fasting plasma glucose, abdominal obesity, high cholesterol and high blood pressure. The goal of this study is to compare the state of the main features of obesity-associated white adipose tissue (WAT) dysfunction in 66 women with severe obesity without (MetS−) or with MetS (MetS+). Fat cell area, adipocyte size distribution and histological fibrosis were analysed in visceral (VAT) and abdominal subcutaneous WAT (SAT) in 33 age- and BMI-matched pairs of MetS− and MetS+ subjects. The mRNA expression of 93 genes implicated in obesity-associated WAT dysfunction was analysed by RT-qPCR in both fat depots. MetS+ females showed higher adipocyte hypertrophy in both fat depots and increased fibrosis and expression of macrophage and hypoxia markers in SAT. Transcriptional data suggest increased fatty acid oxidation in SAT and impaired thermogenesis and extracellular matrix remodelling in VAT from MetS+ subjects. A sPLS-DA model, including SAT expression of PPARA and LEPR genes identified MetS with an AUC = 0.87. Despite equal age, BMI and body composition, MetS+ females display morphological and transcriptional differences in both WAT depots, especially in SAT. These factors may contribute to the transition to MetS. Full article

(This article belongs to the Special Issue Metabolic Syndrome: From Molecular Mechanisms to Novel Therapies)

► Show Figures

Figure 1

22 pages, 5688 KiB

Open AccessArticle

Male and Female Animals Respond Differently to High-Fat Diet and Regular Exercise Training in a Mouse Model of Hyperlipidemia

by Melinda E. Tóth, Brigitta Dukay, Mária Péter, Gábor Balogh, Gergő Szűcs, Ágnes Zvara, Gábor J. Szebeni, Petra Hajdu, Márta Sárközy, László G. Puskás, Zsolt Török, Tamás Csont, László Vígh and Miklós Sántha

Int. J. Mol. Sci. 2021, 22(8), 4198; https://doi.org/10.3390/ijms22084198 - 18 Apr 2021

Cited by 21 | Viewed by 6642

Abstract

Inappropriate nutrition and a sedentary lifestyle can lead to obesity, one of the most common risk factors for several chronic diseases. Although regular physical exercise is an efficient approach to improve cardiometabolic health, the exact cellular processes are still not fully understood. We [...] Read more.

Inappropriate nutrition and a sedentary lifestyle can lead to obesity, one of the most common risk factors for several chronic diseases. Although regular physical exercise is an efficient approach to improve cardiometabolic health, the exact cellular processes are still not fully understood. We aimed to analyze the morphological, gene expression, and lipidomic patterns in the liver and adipose tissues in response to regular exercise. Healthy (wild type on a normal diet) and hyperlipidemic, high-fat diet-fed (HFD-fed) apolipoprotein B-100 (APOB-100)-overexpressing mice were trained by treadmill running for 7 months. The serum concentrations of triglyceride and tumor necrosis factor α (TNFα), as well as the level of lipid accumulation in the liver, were significantly higher in HFD-fed APOB-100 males compared to females. However, regular exercise almost completely abolished lipid accumulation in the liver of hyperlipidemic animals. The expression level of the thermogenesis marker, uncoupling protein-1 (Ucp1), was significantly higher in the subcutaneous white adipose tissue of healthy females, as well as in the brown adipose tissue of HFD-fed APOB-100 females, compared to males. Lipidomic analyses revealed that hyperlipidemia essentially remodeled the lipidome of brown adipose tissue, affecting both the membrane and storage lipid fractions, which was partially restored by exercise in both sexes. Our results revealed more severe metabolic disturbances in HFD-fed APOB-100 males compared to females. However, exercise efficiently reduced the body weight, serum triglyceride levels, expression of pro-inflammatory factors, and hepatic lipid accumulation in our model. Full article

(This article belongs to the Special Issue Metabolic Syndrome: From Molecular Mechanisms to Novel Therapies)

► Show Figures

Figure 1

12 pages, 1893 KiB

Open AccessArticle

Postnatal Catch-Up Growth Programs Telomere Dynamics and Glucose Intolerance in Low Birth Weight Mice

by Eva Pericuesta, Julia L. Gutiérrez-Arroyo, Maria J. Sánchez-Calabuig and Alfonso Gutiérrez-Adán

Int. J. Mol. Sci. 2021, 22(7), 3657; https://doi.org/10.3390/ijms22073657 - 1 Apr 2021

Cited by 8 | Viewed by 2427

Abstract

Low birth weight and rapid postnatal weight gain are independent predictors of obesity and diabetes in adult life, yet the molecular events involved in this process remain unknown. In inbred and outbred mice, this study examines natural intrauterine growth restriction (IUGR) in relation [...] Read more.

Low birth weight and rapid postnatal weight gain are independent predictors of obesity and diabetes in adult life, yet the molecular events involved in this process remain unknown. In inbred and outbred mice, this study examines natural intrauterine growth restriction (IUGR) in relation to body weight, telomere length (TL), glucose tolerance, and growth factor gene (Igf1, Igf2, Insr, Igf1r, and Igf2r) mRNA expression levels in the brain, liver, and muscle at 2- and 10 days of age and then at 3- and 9 months of age. At birth, ~15% of the animals showed IUGR, but by 3 and 9 months, half of these animals had regained the same weight as controls without IUGR (recuperated group). At 10 days, there was no difference in TL between animals undergoing IUGR and controls. However, by 3 and 9 months of age, the recuperated animals had shorter TL than the control and IUGR-non recuperated animals and also showed glucose intolerance. Further, compared to controls, Igf1 and Igf2 growth factor mRNA expression was lower in Day 2-IUGR mice, while Igf2r and Insr mRNA expression was higher in D10-IUGR animals. Moreover, at 3 months of age, only in the recuperated group were brain and liver Igf1, Igf2, Insr, and Igf2r expression levels higher than in the control and IUGR-non-recuperated groups. These data indicate that catch-up growth but not IUGR per se affects TL and glucose tolerance, and suggest a role in this latter process of insulin/insulin-like growth signaling pathway gene expression during early development. Full article

(This article belongs to the Special Issue Metabolic Syndrome: From Molecular Mechanisms to Novel Therapies)

► Show Figures

Figure 1

26 pages, 4344 KiB

Open AccessArticle

Chronic Effects of a High Sucrose Diet on Murine Gastrointestinal Nutrient Sensor Gene and Protein Expression Levels and Lipid Metabolism

by Patrick O’Brien, Ge Han, Priya Ganpathy, Shweta Pitre, Yi Zhang, John Ryan, Pei Ying Sim, Scott V. Harding, Robert Gray, Victor R. Preedy, Thomas A. B. Sanders and Christopher P. Corpe

Int. J. Mol. Sci. 2021, 22(1), 137; https://doi.org/10.3390/ijms22010137 - 25 Dec 2020

Cited by 6 | Viewed by 4489

Abstract

The gastrointestinal tract (GIT) plays a key role in regulating nutrient metabolism and appetite responses. This study aimed to identify changes in the GIT that are important in the development of diet related obesity and diabetes. GIT samples were obtained from C57BL/6J male [...] Read more.

The gastrointestinal tract (GIT) plays a key role in regulating nutrient metabolism and appetite responses. This study aimed to identify changes in the GIT that are important in the development of diet related obesity and diabetes. GIT samples were obtained from C57BL/6J male mice chronically fed a control diet or a high sucrose diet (HSD) and analysed for changes in gene, protein and metabolite levels. In HSD mice, GIT expression levels of fat oxidation genes were reduced, and increased de novo lipogenesis was evident in ileum. Gene expression levels of the putative sugar sensor, slc5a4a and slc5a4b, and fat sensor, cd36, were downregulated in the small intestines of HSD mice. In HSD mice, there was also evidence of bacterial overgrowth and a lipopolysaccharide activated inflammatory pathway involving inducible nitric oxide synthase (iNOS). In Caco-2 cells, sucrose significantly increased the expression levels of the nos2, iNOS and nitric oxide (NO) gas levels. In conclusion, sucrose fed induced obesity/diabetes is associated with changes in GI macronutrient sensing, appetite regulation and nutrient metabolism and intestinal microflora. These may be important drivers, and thus therapeutic targets, of diet-related metabolic disease. Full article

(This article belongs to the Special Issue Metabolic Syndrome: From Molecular Mechanisms to Novel Therapies)

► Show Figures

Figure 1

Review

Jump to: Research

17 pages, 815 KiB

Open AccessReview

Metabolic Alterations in Cellular Senescence: The Role of Citrate in Ageing and Age-Related Disease

by Maria Elzbieta Mycielska, Emma Naomi James and Eric Kenneth Parkinson

Int. J. Mol. Sci. 2022, 23(7), 3652; https://doi.org/10.3390/ijms23073652 - 26 Mar 2022

Cited by 20 | Viewed by 4781

Abstract

Recent mouse model experiments support an instrumental role for senescent cells in age-related diseases and senescent cells may be causal to certain age-related pathologies. A strongly supported hypothesis is that extranuclear chromatin is recognized by the cyclic GMP–AMP synthase-stimulator of interferon genes pathway, [...] Read more.

Recent mouse model experiments support an instrumental role for senescent cells in age-related diseases and senescent cells may be causal to certain age-related pathologies. A strongly supported hypothesis is that extranuclear chromatin is recognized by the cyclic GMP–AMP synthase-stimulator of interferon genes pathway, which in turn leads to the induction of several inflammatory cytokines as part of the senescence-associated secretory phenotype. This sterile inflammation increases with chronological age and age-associated disease. More recently, several intracellular and extracellular metabolic changes have been described in senescent cells but it is not clear whether any of them have functional significance. In this review, we highlight the potential effect of dietary and age-related metabolites in the modulation of the senescent phenotype in addition to discussing how experimental conditions may influence senescent cell metabolism, especially that of energy regulation. Finally, as extracellular citrate accumulates following certain types of senescence, we focus on the recently reported role of extracellular citrate in aging and age-related pathologies. We propose that citrate may be an active component of the senescence-associated secretory phenotype and via its intake through the diet may even contribute to the cause of age-related disease. Full article

(This article belongs to the Special Issue Metabolic Syndrome: From Molecular Mechanisms to Novel Therapies)

► Show Figures

Figure 1

38 pages, 1749 KiB

Open AccessReview

Metabolic Syndrome: Updates on Pathophysiology and Management in 2021

by Gracia Fahed, Laurence Aoun, Morgan Bou Zerdan, Sabine Allam, Maroun Bou Zerdan, Youssef Bouferraa and Hazem I. Assi

Int. J. Mol. Sci. 2022, 23(2), 786; https://doi.org/10.3390/ijms23020786 - 12 Jan 2022

Cited by 570 | Viewed by 70603

Abstract

Metabolic syndrome (MetS) forms a cluster of metabolic dysregulations including insulin resistance, atherogenic dyslipidemia, central obesity, and hypertension. The pathogenesis of MetS encompasses multiple genetic and acquired entities that fall under the umbrella of insulin resistance and chronic low-grade inflammation. If left untreated, [...] Read more.

Metabolic syndrome (MetS) forms a cluster of metabolic dysregulations including insulin resistance, atherogenic dyslipidemia, central obesity, and hypertension. The pathogenesis of MetS encompasses multiple genetic and acquired entities that fall under the umbrella of insulin resistance and chronic low-grade inflammation. If left untreated, MetS is significantly associated with an increased risk of developing diabetes and cardiovascular diseases (CVDs). Given that CVDs constitute by far the leading cause of morbidity and mortality worldwide, it has become essential to investigate the role played by MetS in this context to reduce the heavy burden of the disease. As such, and while MetS relatively constitutes a novel clinical entity, the extent of research about the disease has been exponentially growing in the past few decades. However, many aspects of this clinical entity are still not completely understood, and many questions remain unanswered to date. In this review, we provide a historical background and highlight the epidemiology of MetS. We also discuss the current and latest knowledge about the histopathology and pathophysiology of the disease. Finally, we summarize the most recent updates about the management and the prevention of this clinical syndrome. Full article

(This article belongs to the Special Issue Metabolic Syndrome: From Molecular Mechanisms to Novel Therapies)

► Show Figures

Figure 1

21 pages, 1460 KiB

Open AccessReview

Early-Life Origins of Metabolic Syndrome: Mechanisms and Preventive Aspects

by Chien-Ning Hsu, Chih-Yao Hou, Wei-Hsuan Hsu and You-Lin Tain

Int. J. Mol. Sci. 2021, 22(21), 11872; https://doi.org/10.3390/ijms222111872 - 2 Nov 2021

Cited by 45 | Viewed by 7323

Abstract

One of the leading global public-health burdens is metabolic syndrome (MetS), despite the many advances in pharmacotherapies. MetS, now known as “developmental origins of health and disease” (DOHaD), can have its origins in early life. Offspring MetS can be programmed by various adverse [...] Read more.

One of the leading global public-health burdens is metabolic syndrome (MetS), despite the many advances in pharmacotherapies. MetS, now known as “developmental origins of health and disease” (DOHaD), can have its origins in early life. Offspring MetS can be programmed by various adverse early-life conditions, such as nutrition imbalance, maternal conditions or diseases, maternal chemical exposure, and medication use. Conversely, early interventions have shown potential to revoke programming processes to prevent MetS of developmental origins, namely reprogramming. In this review, we summarize what is currently known about adverse environmental insults implicated in MetS of developmental origins, including the fundamental underlying mechanisms. We also describe animal models that have been developed to study the developmental programming of MetS. This review extends previous research reviews by addressing implementation of reprogramming strategies to prevent the programming of MetS. These mechanism-targeted strategies include antioxidants, melatonin, resveratrol, probiotics/prebiotics, and amino acids. Much work remains to be accomplished to determine the insults that could induce MetS, to identify the mechanisms behind MetS programming, and to develop potential reprogramming strategies for clinical translation. Full article

(This article belongs to the Special Issue Metabolic Syndrome: From Molecular Mechanisms to Novel Therapies)

► Show Figures

Figure 1

13 pages, 2010 KiB

Open AccessReview

Reconnoitering the Role of Long-Noncoding RNAs in Hypertrophic Cardiomyopathy: A Descriptive Review

by Syeda K. Shahzadi, Nerissa Naidoo, Alawi Alsheikh-Ali, Manfredi Rizzo, Ali A. Rizvi, Raul D. Santos and Yajnavalka Banerjee

Int. J. Mol. Sci. 2021, 22(17), 9378; https://doi.org/10.3390/ijms22179378 - 29 Aug 2021

Cited by 9 | Viewed by 3818

Abstract

Hypertrophic cardiomyopathy (HCM) is the most common form of hereditary cardiomyopathy. It is characterized by an unexplained non-dilated hypertrophy of the left ventricle with a conserved or elevated ejection fraction. It is a genetically heterogeneous disease largely caused by variants of genes encoding [...] Read more.

Hypertrophic cardiomyopathy (HCM) is the most common form of hereditary cardiomyopathy. It is characterized by an unexplained non-dilated hypertrophy of the left ventricle with a conserved or elevated ejection fraction. It is a genetically heterogeneous disease largely caused by variants of genes encoding for cardiac sarcomere proteins, including MYH7, MYBPC3, ACTC1, TPM1, MYL2, MYL3, TNNI3, and TNNT23. Preclinical evidence indicates that the enhanced calcium sensitivity of the myofilaments plays a key role in the pathophysiology of HCM. Notably, this is not always a direct consequence of sarcomeric variations but may also result from secondary mutation-driven alterations. Long non-coding RNAs (lncRNAs) are a large class of transcripts ≥200 nucleotides in length that do not encode proteins. Compared to coding mRNAs, most lncRNAs are not as well-annotated and their functions are greatly unexplored. Nevertheless, increasing evidence shows that lncRNAs are involved in a variety of biological processes and diseases including HCM. Accumulating evidence has indicated that lncRNAs are dysregulated in HCM, and closely related to sarcomere construction, calcium channeling and homeostasis of mitochondria. In this review, we have summarized the known regulatory and functional roles of lncRNAs in HCM. Full article

(This article belongs to the Special Issue Metabolic Syndrome: From Molecular Mechanisms to Novel Therapies)

► Show Figures

Figure 1

17 pages, 926 KiB

Open AccessReview

Exploring the Role of Skeletal Muscle in Insulin Resistance: Lessons from Cultured Cells to Animal Models

by Alessandra Feraco, Stefania Gorini, Andrea Armani, Elisabetta Camajani, Manfredi Rizzo and Massimiliano Caprio

Int. J. Mol. Sci. 2021, 22(17), 9327; https://doi.org/10.3390/ijms22179327 - 28 Aug 2021

Cited by 39 | Viewed by 11562

Abstract

Skeletal muscle is essential to maintain vital functions such as movement, breathing, and thermogenesis, and it is now recognized as an endocrine organ. Muscles release factors named myokines, which can regulate several physiological processes. Moreover, skeletal muscle is particularly important in maintaining body [...] Read more.

Skeletal muscle is essential to maintain vital functions such as movement, breathing, and thermogenesis, and it is now recognized as an endocrine organ. Muscles release factors named myokines, which can regulate several physiological processes. Moreover, skeletal muscle is particularly important in maintaining body homeostasis, since it is responsible for more than 75% of all insulin-mediated glucose disposal. Alterations of skeletal muscle differentiation and function, with subsequent dysfunctional expression and secretion of myokines, play a key role in the pathogenesis of obesity, type 2 diabetes, and other metabolic diseases, finally leading to cardiometabolic complications. Hence, a deeper understanding of the molecular mechanisms regulating skeletal muscle function related to energy metabolism is critical for novel strategies to treat and prevent insulin resistance and its cardiometabolic complications. This review will be focused on both cellular and animal models currently available for exploring skeletal muscle metabolism and endocrine function. Full article

(This article belongs to the Special Issue Metabolic Syndrome: From Molecular Mechanisms to Novel Therapies)

► Show Figures

Figure 1

15 pages, 1300 KiB

Open AccessReview

The Role of Glycemic Variability in Cardiovascular Disorders

by Valentina Alfieri, Veronika A. Myasoedova, Maria Cristina Vinci, Maurizio Rondinelli, Paola Songia, Ilaria Massaiu, Nicola Cosentino, Donato Moschetta, Vincenza Valerio, Michele Ciccarelli, Giancarlo Marenzi, Stefano Genovese and Paolo Poggio

Int. J. Mol. Sci. 2021, 22(16), 8393; https://doi.org/10.3390/ijms22168393 - 4 Aug 2021

Cited by 32 | Viewed by 4508

Abstract

Diabetes mellitus (DM) is one of the most common and costly disorders that affect humans around the world. Recently, clinicians and scientists have focused their studies on the effects of glycemic variability (GV), which is especially associated with cardiovascular diseases. In healthy subjects, [...] Read more.

Diabetes mellitus (DM) is one of the most common and costly disorders that affect humans around the world. Recently, clinicians and scientists have focused their studies on the effects of glycemic variability (GV), which is especially associated with cardiovascular diseases. In healthy subjects, glycemia is a very stable parameter, while in poorly controlled DM patients, it oscillates greatly throughout the day and between days. Clinically, GV could be measured by different parameters, but there are no guidelines on standardized assessment. Nonetheless, DM patients with high GV experience worse cardiovascular disease outcomes. In vitro and in vivo studies showed that high GV causes several detrimental effects, such as increased oxidative stress, inflammation, and apoptosis linked to endothelial dysfunction. However, the evidence that treating GV is beneficial is still scanty. Clinical trials aiming to improve the diagnostic and prognostic accuracy of GV measurements correlated with cardiovascular outcomes are needed. The present review aims to evaluate the clinical link between high GV and cardiovascular diseases, taking into account the underlined biological mechanisms. A clear view of this challenge may be useful to standardize the clinical evaluation and to better identify treatments and strategies to counteract this DM aspect. Full article

(This article belongs to the Special Issue Metabolic Syndrome: From Molecular Mechanisms to Novel Therapies)

► Show Figures

Graphical abstract

12 pages, 550 KiB

Open AccessReview

The Evolving Role of Fetuin-A in Nonalcoholic Fatty Liver Disease: An Overview from Liver to the Heart

by Teoman Dogru, Ali Kirik, Hasan Gurel, Ali A. Rizvi, Manfredi Rizzo and Alper Sonmez

Int. J. Mol. Sci. 2021, 22(12), 6627; https://doi.org/10.3390/ijms22126627 - 21 Jun 2021

Cited by 19 | Viewed by 4322

Abstract

Nonalcoholic fatty liver disease (NAFLD) is strongly associated to the features of metabolic syndrome which can progress to cirrhosis, liver failure and hepatocellular carcinoma. However, the most common cause of mortality in people with NAFLD is not liver-related but stems from atherosclerotic cardiovascular [...] Read more.

Nonalcoholic fatty liver disease (NAFLD) is strongly associated to the features of metabolic syndrome which can progress to cirrhosis, liver failure and hepatocellular carcinoma. However, the most common cause of mortality in people with NAFLD is not liver-related but stems from atherosclerotic cardiovascular disease (CVD). The prevalence of NAFLD is on the rise, mainly as a consequence of its close association with two major worldwide epidemics, obesity and type 2 diabetes (T2D). The exact pathogenesis of NAFLD and especially the mechanisms leading to disease progression and CVD have not been completely elucidated. Human fetuin-A (alpha-2-Heremans Schmid glycoprotein), a glycoprotein produced by the liver and abundantly secreted into the circulation appears to play a role in insulin resistance, metabolic syndrome and inflammation. This review discusses the links between NAFLD and CVD by specifically focusing on fetuin-A’s function in the pathogenesis of NAFLD and atherosclerotic CVD. Full article

(This article belongs to the Special Issue Metabolic Syndrome: From Molecular Mechanisms to Novel Therapies)

► Show Figures

Figure 1

20 pages, 407 KiB

Open AccessReview

Epigenetics, microRNA and Metabolic Syndrome: A Comprehensive Review

by Farha Ramzan, Mark H. Vickers and Richard F. Mithen

Int. J. Mol. Sci. 2021, 22(9), 5047; https://doi.org/10.3390/ijms22095047 - 10 May 2021

Cited by 53 | Viewed by 7068

Abstract

Epigenetics refers to the DNA chemistry changes that result in the modification of gene transcription and translation independently of the underlying DNA coding sequence. Epigenetic modifications are reported to involve various molecular mechanisms, including classical epigenetic changes affecting DNA methylation and histone modifications [...] Read more.

Epigenetics refers to the DNA chemistry changes that result in the modification of gene transcription and translation independently of the underlying DNA coding sequence. Epigenetic modifications are reported to involve various molecular mechanisms, including classical epigenetic changes affecting DNA methylation and histone modifications and small RNA-mediated processes, particularly that of microRNAs. Epigenetic changes are reversible and are closely interconnected. They are recognised to play a critical role as mediators of gene regulation, and any alteration in these mechanisms has been identified to mediate various pathophysiological conditions. Moreover, genetic predisposition and environmental factors, including dietary alterations, lifestyle or metabolic status, are identified to interact with the human epigenome, highlighting the importance of epigenetic factors as underlying processes in the aetiology of various diseases such as MetS. This review will reflect on how both the classical and microRNA-regulated epigenetic changes are associated with the pathophysiology of metabolic syndrome. We will then focus on the various aspects of epigenetic-based strategies used to modify MetS outcomes, including epigenetic diet, epigenetic drugs, epigenome editing tools and miRNA-based therapies. Full article

(This article belongs to the Special Issue Metabolic Syndrome: From Molecular Mechanisms to Novel Therapies)

19 pages, 1015 KiB

Open AccessReview

Genetics of Cardiovascular Disease: How Far Are We from Personalized CVD Risk Prediction and Management?

by Michal Vrablik, Dana Dlouha, Veronika Todorovova, Denes Stefler and Jaroslav A. Hubacek

Int. J. Mol. Sci. 2021, 22(8), 4182; https://doi.org/10.3390/ijms22084182 - 17 Apr 2021

Cited by 30 | Viewed by 9372

Abstract

Despite the rapid progress in diagnosis and treatment of cardiovascular disease (CVD), this disease remains a major cause of mortality and morbidity. Recent progress over the last two decades in the field of molecular genetics, especially with new tools such as genome-wide association [...] Read more.

Despite the rapid progress in diagnosis and treatment of cardiovascular disease (CVD), this disease remains a major cause of mortality and morbidity. Recent progress over the last two decades in the field of molecular genetics, especially with new tools such as genome-wide association studies, has helped to identify new genes and their variants, which can be used for calculations of risk, prediction of treatment efficacy, or detection of subjects prone to drug side effects. Although the use of genetic risk scores further improves CVD prediction, the significance is not unambiguous, and some subjects at risk remain undetected. Further research directions should focus on the “second level” of genetic information, namely, regulatory molecules (miRNAs) and epigenetic changes, predominantly DNA methylation and gene-environment interactions. Full article

(This article belongs to the Special Issue Metabolic Syndrome: From Molecular Mechanisms to Novel Therapies)

► Show Figures

Figure 1

13 pages, 1890 KiB

Open AccessReview

Glucagon-Like Peptide 1 and Taste Perception: From Molecular Mechanisms to Potential Clinical Implications

by Mojca Jensterle, Manfredi Rizzo and Andrej Janez

Int. J. Mol. Sci. 2021, 22(2), 902; https://doi.org/10.3390/ijms22020902 - 18 Jan 2021

Cited by 13 | Viewed by 5280

Abstract

Preclinical studies provided some important insights into the action of glucagon-like peptide 1 (GLP-1) in taste perception. This review examines the literature to uncover some molecular mechanisms and connections between GLP-1 and the gustatory coding. Local GLP-1 production in the taste bud cells, [...] Read more.

Preclinical studies provided some important insights into the action of glucagon-like peptide 1 (GLP-1) in taste perception. This review examines the literature to uncover some molecular mechanisms and connections between GLP-1 and the gustatory coding. Local GLP-1 production in the taste bud cells, the expression of GLP-1 receptor on the adjacent nerves, a functional continuum in the perception of sweet chemicals from the gut to the tongue and an identification of GLP-1 induced signaling pathways in peripheral and central gustatory coding all strongly suggest that GLP-1 is involved in the taste perception, especially sweet. However, the impact of GLP-1 based therapies on gustatory coding in humans remains largely unaddressed. Based on the molecular background we encourage further exploration of the tongue as a new treatment target for GLP-1 receptor agonists in clinical studies. Given that pharmacological manipulation of gustatory coding may represent a new potential strategy against obesity and diabetes, the topic is of utmost clinical relevance. Full article

(This article belongs to the Special Issue Metabolic Syndrome: From Molecular Mechanisms to Novel Therapies)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Metabolic Syndrome: From Molecular Mechanisms to Novel Therapies

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (14 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI