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Effects of the Treatment with Flavonoids on Metabolic Syndrome Components in Humans: A Systematic Review Focusing on Mechanisms of Action.
Gouveia, HJCB, Urquiza-Martínez, MV, Manhães-de-Castro, R, Costa-de-Santana, BJR, Villarreal, JP, Mercado-Camargo, R, Torner, L, de Souza Aquino, J, Toscano, AE, Guzmán-Quevedo, O
International journal of molecular sciences. 2022;23(15)
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Metabolic syndrome is a condition characterised by at least three of the five risk factors, such as abdominal obesity, elevated fasting glucose, blood pressure and triglycerides and reduced high-density lipoprotein cholesterol (HDL-c). There is a strong link between metabolic syndrome and the development of cardiovascular disease and Type 2 diabetes. Research suggests that increasing consumption of flavonoid-rich foods can be beneficial in reducing cardiovascular morbidity and mortality. Flavonoids are bioactive compounds that possess antioxidative, anti-inflammatory, anti-cancerous, anti-mutagenic, and enzymatic properties. This systematic review of 29 randomised controlled trials evaluated the beneficial effects of long-term flavonoid supplementation in reducing the risk factors of metabolic syndrome. This review included a variety of flavonoid supplements, such as anthocyanin, hesperidin, quercetin, epigallocatechin gallate (egcg), genistein, theaflavin, catechin, and eriocitrin. Additionally, this research investigated the mechanisms behind the beneficial effects of flavonoid supplementation. Results showed that flavonoid supplementation for at least three weeks improved metabolic parameters and inflammatory markers, with hesperidin showing the greatest improvements in metabolic parameters. Healthcare professionals can use these findings to understand the potential benefits of long-term flavonoid supplementation in improving metabolic parameters. However, more robust studies are needed to determine the therapeutic dosages of different flavonoids.
Abstract
Diets high in bioactive compounds, such as polyphenols, have been used to mitigate metabolic syndrome (MetS). Polyphenols are a large group of naturally occurring bioactive compounds, classified into two main classes: non-flavonoids and flavonoids. Flavonoids are distributed in foods, such as fruits, vegetables, tea, red wine, and cocoa. Studies have already demonstrated the benefits of flavonoids on the cardiovascular and nervous systems, as well as cancer cells. The present review summarizes the results of clinical studies that evaluated the effects of flavonoids on the components of the MetS and associated complications when offered as supplements over the long term. The results show that flavonoids can significantly modulate several metabolic parameters, such as lipid profile, blood pressure, and blood glucose. Only theaflavin and catechin were unable to affect metabolic parameters. Moreover, only body weight and body mass index were unaltered. Thus, the evidence presented in this systematic review offers bases in support of a flavonoid supplementation, held for at least 3 weeks, as a strategy to improve several metabolic parameters and, consequently, reduce the risk of diseases associated with MetS. This fact becomes stronger due to the rare side effects reported with flavonoids.
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The Gut Microbiota (Microbiome) in Cardiovascular Disease and Its Therapeutic Regulation.
Rahman, MM, Islam, F, -Or-Rashid, MH, Mamun, AA, Rahaman, MS, Islam, MM, Meem, AFK, Sutradhar, PR, Mitra, S, Mimi, AA, et al
Frontiers in cellular and infection microbiology. 2022;12:903570
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Cardiovascular disease (CVD) accounts for 31% of all-cause mortality worldwide. Irregularities in the composition of intestinal microbial composition, genetic factors, nutrition, metabolic irregularities, and smoking are among the potential causes of CVD. Intestinal permeability and translocation of endotoxins and bacterial metabolites to systemic circulation may trigger an immune response and inflammation, which may increase the risk of CVD. Synthesis of bacterial metabolites such as trimethylamine N-oxide (TMAO) by choline-inducing gut bacteria and reduced consumption of dietary TMAO precursors may elevate the CVD risk. This review explores the latest research on the role of gut microbiota in the development of atherosclerosis and CVD, as well as potential strategies to prevent CVD by targeting TMAO-producing gut bacteria. Elevated levels of TMAO in the bloodstream can lead to the buildup of cholesterol and ultimately result in atherosclerosis. However, consuming probiotics and fibre-rich foods can help regulate gut bacteria, reduce inflammation, and improve lipid profiles, all of which contribute to better cardiovascular health. More future robust studies are required to examine the mechanistic insights and confirm whether TMAO can serve as a biomarker for preventing CVD through the therapeutic modulation of intestinal bacteria.
Abstract
In the last two decades, considerable interest has been shown in understanding the development of the gut microbiota and its internal and external effects on the intestine, as well as the risk factors for cardiovascular diseases (CVDs) such as metabolic syndrome. The intestinal microbiota plays a pivotal role in human health and disease. Recent studies revealed that the gut microbiota can affect the host body. CVDs are a leading cause of morbidity and mortality, and patients favor death over chronic kidney disease. For the function of gut microbiota in the host, molecules have to penetrate the intestinal epithelium or the surface cells of the host. Gut microbiota can utilize trimethylamine, N-oxide, short-chain fatty acids, and primary and secondary bile acid pathways. By affecting these living cells, the gut microbiota can cause heart failure, atherosclerosis, hypertension, myocardial fibrosis, myocardial infarction, and coronary artery disease. Previous studies of the gut microbiota and its relation to stroke pathogenesis and its consequences can provide new therapeutic prospects. This review highlights the interplay between the microbiota and its metabolites and addresses related interventions for the treatment of CVDs.
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The Effect of Ketogenic Diet on Shared Risk Factors of Cardiovascular Disease and Cancer.
Mohammadifard, N, Haghighatdoost, F, Rahimlou, M, Rodrigues, APS, Gaskarei, MK, Okhovat, P, de Oliveira, C, Silveira, EA, Sarrafzadegan, N
Nutrients. 2022;14(17)
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Cardiovascular disease and cancer are major causes of mortality worldwide and share common pathophysiological mechanisms and risk factors. The ketogenic diet, a low-carbohydrate and high-fat diet, may alter metabolic pathways, potentially lowering the risk of developing these diseases. Specifically, the ketogenic diet improves energy metabolism by promoting the use of body ketones for energy production. This review examines the protective effects of the ketogenic diet in reducing cardiovascular disease and cancer risk and explores the underlying mechanisms. The ketogenic diet may suppress oxidative stress and inflammation while improving common risk factors such as obesity, hypertension, diabetes, and dyslipidaemia. It is important to conduct further rigorous studies to assess the long-term effects of the ketogenic diet. However, healthcare professionals can use these findings to understand the short-term benefits of the diet in managing metabolic abnormalities and reducing the risk of developing cardiovascular disease and cancer.
Abstract
Cardiovascular disease (CVD) and cancer are the first and second leading causes of death worldwide, respectively. Epidemiological evidence has demonstrated that the incidence of cancer is elevated in patients with CVD and vice versa. However, these conditions are usually regarded as separate events despite the presence of shared risk factors between both conditions, such as metabolic abnormalities and lifestyle. Cohort studies suggested that controlling for CVD risk factors may have an impact on cancer incidence. Therefore, it could be concluded that interventions that improve CVD and cancer shared risk factors may potentially be effective in preventing and treating both diseases. The ketogenic diet (KD), a low-carbohydrate and high-fat diet, has been widely prescribed in weight loss programs for metabolic abnormalities. Furthermore, recent research has investigated the effects of KD on the treatment of numerous diseases, including CVD and cancer, due to its role in promoting ketolysis, ketogenesis, and modifying many other metabolic pathways with potential favorable health effects. However, there is still great debate regarding prescribing KD in patients either with CVD or cancer. Considering the number of studies on this topic, there is a clear need to summarize potential mechanisms through which KD can improve cardiovascular health and control cell proliferation. In this review, we explained the history of KD, its types, and physiological effects and discussed how it could play a role in CVD and cancer treatment and prevention.
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Vegetarian and Vegan Diet in Fibromyalgia: A Systematic Review.
Nadal-Nicolás, Y, Miralles-Amorós, L, Martínez-Olcina, M, Sánchez-Ortega, M, Mora, J, Martínez-Rodríguez, A
International journal of environmental research and public health. 2021;18(9)
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Fibromyalgia (FM) is a chronic non-degenerative disease of unknown etiology without effective medical treatment that mostly affects women. The aim of this study was to evaluate the efficacy of mainly plant-based diets in patients with FM compared to omnivorous diets. A secondary aim was to examine the main effects of these diets on patients’ symptoms and the improvement in their quality of life. This study is a systemic review of six studies (n = 4 clinical trials and n = 2 observational cohort studies). The selected studies included 157 FM patients in both the intervention and control groups, and more than 117 were women. Results indicate that a mainly plant-based diet improves biochemical parameters and body inflammation; body weight, sleep quality, quality of life, pain at rest as well as other symptoms of FM and their impact on health. Authors conclude that even though their findings are promising further well-designed clinical trials are needed to consolidate these dietary recommendations in FM patient.
Abstract
Fibromyalgia (FM) is a chronic non-degenerative disease characterized by the presence of multiple symptoms such as chronic pain, which negatively influence the quality of life of sufferers, most of whom are women. Currently, there is no effective treatment to limit the impact of these symptoms. The aim of this research is to review the scientific evidence on the effect of following a vegetarian or vegan diet on fibromyalgia patients. A systematic review included the original articles that answered the research question. These articles were in 2021 in the PubMed, Web of Science and Scopus databases. The research used the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. No time restriction was applied, and grey literature was not included. The evaluation of the methodological quality of the articles was carried out using the following different scales: STROBE (strengthening the reporting of observational studies in epidemiology), PEDro (Physiotherapy Evidence Database), and MMAT (Mixed Methods Appraisal Tool) scales. A total of 88 studies were analyzed, of which 6 investigations were included in this systematic review (n = 4 clinical trials and n = 2 cohort studies). These investigations show significant improvements in biochemical parameters, quality of life, quality of sleep, pain at rest and general health status when following mainly plant-based dietary patterns. In conclusion, these findings are promising but interpretation of the findings is limited due to the methodological quality of the studies. Well-designed clinical trials are needed to consolidate these dietary recommendations in FM patients.
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Anti-aging Effects of Calorie Restriction (CR) and CR Mimetics based on the Senoinflammation Concept.
Kim, DH, Bang, E, Jung, HJ, Noh, SG, Yu, BP, Choi, YJ, Chung, HY
Nutrients. 2020;12(2)
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Low grade, systemic, chronic inflammation is a feature of ageing and underlies many age-related chronic diseases states. As cells age their capacity to proliferate declines, which is referred to as cell senescence. Such senescent cells release multiple inflammatory markers contributing to a pro-inflammatory state. This is further aggravated by elevated oxidative stress and a reduced capacity to manage it, eventually leading to improper gene regulation and DNA damage. To define this age-related, complex inflammatory phenomena the authors introduced the term senoinflammation. A well-established intervention to reverse or slow down the ageing process and many ageing-associated diseases is calorie restriction (CR), by means of reducing overall caloric intake without malnutrition. CR exhibits potent anti-inflammatory effects, reduces age-associated oxidative stress, improves age-related metabolic dysregulation and enhances favourable gene expression. This review summarises how CR and CR-mimicking substances exert their anti-inflammatory effect and some of the cellular mechanism involved and may be of interest to those who are looking to get a more detailed understanding on ageing, inflammation and the benefits of CR.
Abstract
Chronic inflammation, a pervasive feature of the aging process, is defined by a continuous, multifarious, low-grade inflammatory response. It is a sustained and systemic phenomenon that aggravates aging and can lead to age-related chronic diseases. In recent years, our understanding of age-related chronic inflammation has advanced through a large number of investigations on aging and calorie restriction (CR). A broader view of age-related inflammation is the concept of senoinflammation, which has an outlook beyond the traditional view, as proposed in our previous work. In this review, we discuss the effects of CR on multiple phases of proinflammatory networks and inflammatory signaling pathways to elucidate the basic mechanism underlying aging. Based on studies on senoinflammation and CR, we recognized that senescence-associated secretory phenotype (SASP), which mainly comprises cytokines and chemokines, was significantly increased during aging, whereas it was suppressed during CR. Further, we recognized that cellular metabolic pathways were also dysregulated in aging; however, CR mimetics reversed these effects. These results further support and enhance our understanding of the novel concept of senoinflammation, which is related to the metabolic changes that occur in the aging process. Furthermore, a thorough elucidation of the effect of CR on senoinflammation will reveal key insights and allow possible interventions in aging mechanisms, thus contributing to the development of new therapies focused on improving health and longevity.
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Obesity, Cardiovascular Disease, and Influenza: How Are They Connected?
Gutiérrez-Spillari, L, Palma M, G, Aceituno-Melgar, J
Current tropical medicine reports. 2020;7(3):92-97
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Retrospective studies demonstrate that during the 2009 H1N1 pandemic, obesity was identified as a risk factor for hospitalization, mechanical ventilation, and mortality upon infection. This study is a review which focuses on how obesity and cardiovascular disease impact influenza response. A higher body mass index and metabolic syndrome in patients with influenza have shown an increased risk and length of hospitalization, increased disease severity, morbidity, and mortality during lower respiratory tract infections. Obesity causes a chronic state of inflammation in a generalized and constant way with negative effects on immunity. In fact, obese people have delayed immune responses to influenza virus infection and experience slower recovery from the disease. Thus, recent recommendation advocates the priority of vaccination against influenza in obese patients. Furthermore, cardiovascular diseases, such as ischemic heart disease and heart failure combined with influenza A infection, can trigger acute heart failure exacerbations that increase the overall mortality in a hospitalized setting. The cardioprotective mechanism of influenza vaccination may not function effectively in obese cohorts, thus authors conclude that in order to prevent these complications and in the absence of special consideration treatments for this population, a weight-loss approach is highly recommended.
Abstract
PURPOSE OF REVIEW To better understand the impact of obesity and cardiovascular diseases on influenza A infection. RECENT FINDINGS This infection could have detrimental outcomes in obese patients with cardiovascular diseases, such as an increased risk, length of hospitalization, disease severity, morbidity, and mortality. Nevertheless, there also might be some cardioprotective benefits associated with influenza vaccination, such as a reduced mortality, hospitalization, and acute coronary syndromes, in patients with coronary heart disease and/or heart failure. SUMMARY Obesity negatively impacts immune function and host defense. Recent studies report obesity to be an independent risk factor for increased morbidity and mortality following infection. Obese patients might need special considerations in the treatment; however, there is not enough evidence to fully comprehend the mechanisms behind the reduced immunocompetence when influenza A infection occurs. Future studies should focus on special consideration treatments when the patients have not been vaccinated and have cardiovascular diseases.
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Non-nutritive Sweeteners and Their Associations with Obesity and Type 2 Diabetes.
Walbolt, J, Koh, Y
Journal of obesity & metabolic syndrome. 2020;29(2):114-123
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Nutritive sweeteners (NS) contribute to overall caloric intake, and their adverse effects on metabolic health are well known. Non-nutritive sweeteners (NNS) on the other hand, have negligible or no calorific value and are therefore used as replacement of NS to negate their associated health risks. Whilst the consumption of NNS has steadily increased over the recent years, so has the evidence questioning their benefits. Some research suggesting that NNS could be an indirect contributor to the development of metabolic diseases. This review presents a brief compilation of current knowledge relating to NNS and metabolic syndrome, obesity, type 2 diabetes, and cardiovascular disease. Summarised are findings from randomised controlled trials (RCT), prospective cohort studies, observations from animal studies and recent microbiome research. The authors noted that NNS frequently exerted negative influences on health in prospective cohort studies, which observed selected population groups over time. Whilst in controlled trials, NNS often showed neutral or positive health benefits. Following a discussion of possible causes leading to such variations and conflicting outcomes, the authors called for more carefully designed studies to evaluate NNS and their metabolic influences. For clinicians, it may be worth considering further evidence relating to the individual types of sweeteners when evaluating NNS and their risks and benefits on cardiometabolic health.
Abstract
Evidence linking the excessive consumption of nutritive sweeteners (NS) to adverse metabolic health outcomes has led to an increase in consumption of non-nutritive sweeteners (NNS), particularly among the obese and individuals with diabetes. NNS are characterized by having zero-to-negligible caloric load, while also having a sweet taste. They are utilized as a replacement for traditional NS to reduce energy intake and to limit carbohydrate-related negative health outcomes. However, recent studies have suggested that NNS may actually contribute to the development or worsening of metabolic diseases, including metabolic syndrome, obesity, type 2 diabetes, and cardiovascular disease. Thus, it is imperative to understand the NNS efficacy and the relationship between NNS and metabolic diseases.
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Consumption of ultra-processed foods and health outcomes: a systematic review of epidemiological studies.
Chen, X, Zhang, Z, Yang, H, Qiu, P, Wang, H, Wang, F, Zhao, Q, Fang, J, Nie, J
Nutrition journal. 2020;19(1):86
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Unhealthy diets are recognized as a major determinant of the occurrence of non-communicable diseases (NCDs). The aim of this study was to summarize the evidence for the association between ultra-processed food (UPFs) consumption and health outcomes. This study is a systemic review of 20 published epidemiological studies (12 cohort and 8 cross-sectional studies), with a total of 334,114 participants and 10 diseases. Results indicate a positive association between UPFs consumption and risk of all-cause mortality, overall cardiovascular diseases, coronary heart diseases, cerebrovascular diseases, hypertension, metabolic syndrome, overweight and obesity, depression, irritable bowel syndrome, overall cancer, postmenopausal breast cancer, gestational obesity, adolescent asthma and wheezing, and frailty. However, on the contrary, there was not an obvious association with cardiovascular disease mortality, prostate and colorectal cancer, gestational diabetes mellitus and gestational overweight. Authors conclude that their findings encouraged a decrease in UPFs consumption and an increase in the proportion of unprocessed or minimally processed foods, such as fruits and vegetables.
Abstract
BACKGROUND Consumption of ultra-processed foods (UPFs) plays a potential role in the development of obesity and other diet-related noncommunicable diseases (NCDs), but no studies have systematically focused on this. This study aimed to summarize the evidence for the association between UPFs consumption and health outcomes. METHODS A comprehensive search was conducted in PubMed, Embase, and Web of Science to identify all relevant studies. Epidemiological studies were included, and identified studies were evaluated for risk of bias.A narrative review of the synthesized findings was provided to assess the association between UPFs consumption and health outcomes. RESULTS 20 studies (12 cohort and 8 cross-sectional studies) were included in the analysis, with a total of 334,114 participants and 10 health outcomes. In a narrative review, high UPFs consumption was obviously associated with an increased risk of all-cause mortality, overall cardiovascular diseases, coronary heart diseases, cerebrovascular diseases, hypertension, metabolic syndrome, overweight and obesity, depression, irritable bowel syndrome, overall cancer, postmenopausal breast cancer, gestational obesity, adolescent asthma and wheezing, and frailty. It showed no significant association with cardiovascular disease mortality, prostate and colorectal cancers, gestational diabetes mellitus and gestational overweight. CONCLUSIONS This study indicated a positive association between UPFs consumption and risk of several health outcomes. Large-scale prospective designed studies are needed to confirm our findings.
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Dietary Fructose and the Metabolic Syndrome.
Taskinen, MR, Packard, CJ, Borén, J
Nutrients. 2019;11(9)
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Fructose is a naturally occurring sugar in carbohydrate foods and is often used as an ingredient in foods and sugar sweetened beverages (SSB) such as sport and energy drinks. The consumption of these drinks accounts for up to 15-17% of calorie intake in the modern western diet. Excessive sugar consumption is becoming a major public health issue with high sugar intake linked to Metabolic Syndrome (MetS), cardiovascular disease, type II diabetes and non-alcoholic fatty liver disease. Fructose is largely absorbed in the small intestines however the liver is considered the major organ for fructose metabolism. Too much fructose in the diet appears to stimulate the liver to produce more sugars and triglyceride fats which can raise cholesterol levels and promote insulin resistance. This partially explains the role of fructose in promoting a build-up of fat around the liver leading to non-alcoholic fatty liver disease and central obesity. Too much fructose is also linked to unfavourable changes in gut bacteria which may contribute to obesity and MetS. Overall the study concludes that too much fructose contributes to an unhealthy lifestyle and is a risk factor for metabolic disturbances.
Abstract
Abstract: Consumption of fructose, the sweetest of all naturally occurring carbohydrates, has increased dramatically in the last 40 years and is today commonly used commercially in soft drinks, juice, and baked goods. These products comprise a large proportion of the modern diet, in particular in children, adolescents, and young adults. A large body of evidence associate consumption of fructose and other sugar-sweetened beverages with insulin resistance, intrahepatic lipid accumulation, and hypertriglyceridemia. In the long term, these risk factors may contribute to the development of type 2 diabetes and cardiovascular diseases. Fructose is absorbed in the small intestine and metabolized in the liver where it stimulates fructolysis, glycolysis, lipogenesis, and glucose production. This may result in hypertriglyceridemia and fatty liver. Therefore, understanding the mechanisms underlying intestinal and hepatic fructose metabolism is important. Here we review recent evidence linking excessive fructose consumption to health risk markers and development of components of the Metabolic Syndrome.
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Non-Nutritive Sweeteners and Their Implications on the Development of Metabolic Syndrome.
Liauchonak, I, Qorri, B, Dawoud, F, Riat, Y, Szewczuk, MR
Nutrients. 2019;11(3)
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Artificial sweeteners, such as aspartame, neotame, saccharin, sucralose, and stevia are widely promoted as low-calorie alternatives to sugar and are known as non-nutritive sweeteners (NNS). Generally, they have been considered as a healthy option to replace sugars, but data is emerging that they may influence obesity and metabolic syndrome (METs) and contribute to the development of type II diabetes. These non-nutritive sweeteners can be thousands of times sweeter than sugar and have been widely adopted by the food industry to help reduce calories, and promote weight loss and diabetic products. It is believed that 25% of children and 41% of adults consume low-calorie sweeteners regularly, with the beverage industry relying heavily on them. However, it is now been shown that these sweeteners can cause imbalances to gut bacteria and interact with taste receptors and insulin signalling. These findings mean that artificial sweeteners may trigger the same hormonal response as sugar by releasing insulin and overtime lead to insulin resistance, obesity, and overall metabolic syndrome. Finally, there is evidence that our body develops a learned response to sweeteners which paradoxically leads to weight gain.
Abstract
Individuals widely use non-nutritive sweeteners (NNS) in attempts to lower their overall daily caloric intake, lose weight, and sustain a healthy diet. There are insufficient scientific data that support the safety of consuming NNS. However, recent studies have suggested that NNS consumption can induce gut microbiota dysbiosis and promote glucose intolerance in healthy individuals that may result in the development of type 2 diabetes mellitus (T2DM). This sequence of events may result in changes in the gut microbiota composition through microRNA (miRNA)-mediated changes. The mechanism(s) by which miRNAs alter gene expression of different bacterial species provides a link between the consumption of NNS and the development of metabolic changes. Another potential mechanism that connects NNS to metabolic changes is the molecular crosstalk between the insulin receptor (IR) and G protein-coupled receptors (GPCRs). Here, we aim to highlight the role of NNS in obesity and discuss IR-GPCR crosstalk and miRNA-mediated changes, in the manipulation of the gut microbiota composition and T2DM pathogenesis.