Chrononutrition in the Prevention and Management of Metabolic Disorders: A Literature Review.

BACKGROUND: The concept of time-restricted eating (TRE) or time-restricted feeding (TRF) promotes daily periods of feeding and fasting to determine whole-body physiology. Chronic misalignment of circadian rhythms or chrono-disruption is related to an increased risk of diverse metabolic disorders. The progression of non-communicable diseases seems to be affected by the timing of meals. As a result, intermittent fasting is a promising approach for their management. The aim of the present literature review is to examine and scrutinize the TRE protocols in the fields of prevention and management of metabolic disorders. METHODS: This is a thorough literature review of the reported associations among circadian rhythm, metabolic disorders, diabetes mellitus, obesity, TRE, TRF, dietary habits, circadian disruption, cardiovascular diseases, atherosclerosis, and non-alcoholic fatty liver to find the already existing clinical studies from the last decade (2014-2024) in the most precise scientific online databases, using relevant specific keywords. Several inclusion and exclusion criteria were applied to scrutinize only longitudinal, cross-sectional, descriptive, and prospective clinical human studies. RESULTS: The currently available clinical findings remain scarce and suggest that chrononutrition behaviors such as TRE or TRF may promote several metabolic benefits, mainly in body weight control and fat loss. Improvements in glucose levels and lipid profiles are currently quite controversial since some clinical studies show little or no effect. As far as liver diseases are concerned, the efficacy of intermittent fasting seems to be stronger in the management of non-alcoholic fatty liver disease due to body weight decline and fat loss. CONCLUSIONS: Even if there has been a gradual increase in clinical studies in the last few years, providing promising perspectives, currently, there is no conclusive evidence for the role of chrononutrition in metabolic disorders. Future studies should be well-designed with longer duration and larger sample sizes. Moreover, it is important to examine the best timing of the eating window and its feasibility.

Targeting Metabolic Diseases: The Role of Nutraceuticals in Modulating Oxidative Stress and Inflammation.

The escalating prevalence of metabolic and cardiometabolic disorders, often characterized by oxidative stress and chronic inflammation, poses significant health challenges globally. As the traditional therapeutic approaches may sometimes fall short in managing these health conditions, attention is growing toward nutraceuticals worldwide; with compounds being obtained from natural sources with potential therapeutic beneficial effects being shown to potentially support and, in some cases, replace pharmacological treatments, especially for individuals who do not qualify for conventional pharmacological treatments. This review delves into the burgeoning field of nutraceutical-based pharmacological modulation as a promising strategy for attenuating oxidative stress and inflammation in metabolic and cardiometabolic disorders. Drawing from an extensive body of research, the review showcases various nutraceutical agents, such as polyphenols, omega-3 fatty acids, and antioxidants, which exhibit antioxidative and anti-inflammatory properties. All these can be classified as novel nutraceutical-based drugs that are capable of regulating pathways to mitigate oxidative-stress- and inflammation-associated metabolic diseases. By exploring the mechanisms through which nutraceuticals interact with oxidative stress pathways and immune responses, this review highlights their potential to restore redox balance and temper chronic inflammation. Additionally, the challenges and prospects of nutraceutical-based interventions are discussed, encompassing bioavailability enhancement, personalized treatment approaches, and clinical translation. Through a comprehensive analysis of the latest scientific reports, this article underscores the potential of nutraceutical-based pharmacological treatment modulation as a novel avenue to fight oxidative stress and inflammation in the complex landscape of metabolic disorders, particularly accentuating their impact on cardiovascular health.

Maternal Phlorizin Intake Protects Offspring from Maternal Obesity-Induced Metabolic Disorders in Mice via Targeting Gut Microbiota to Activate the SCFA-GPR43 Pathway.

Maternal obesity increases the risk of obesity and metabolic disorders (MDs) in offspring, which can be mediated by the gut microbiota. Phlorizin (PHZ) can improve gut dysbiosis and positively affect host health; however, its transgenerational metabolic benefits remain largely unclear. This study aimed to investigate the potential of maternal PHZ intake in attenuating the adverse impacts of a maternal high-fat diet on obesity-related MDs in dams and offspring. The results showed that maternal PHZ reduced HFD-induced body weight gain and fat accumulation and improved glucose intolerance and abnormal lipid profiles in both dams and offspring. PHZ improved gut dysbiosis by promoting expansion of SCFA-producing bacteria, Akkermansia and Blautia, while inhibiting LPS-producing and pro-inflammatory bacteria, resulting in significantly increased fecal SCFAs, especially butyric acid, and reduced serum lipopolysaccharide levels and intestinal inflammation. PHZ also promoted intestinal GLP-1/2 secretion and intestinal development and enhanced gut barrier function by activating G protein-coupled receptor 43 (GPR43) in the offspring. Antibiotic-treated mice receiving FMT from PHZ-regulated offspring could attenuate MDs induced by receiving FMT from HFD offspring through the gut microbiota to activate the GPR43 pathway. It can be regarded as a promising functional food ingredient for preventing intergenerational transmission of MDs and breaking the obesity cycle.

Preventing metabolic disease: Part I.

While the successes of modern medicine have significantly extended the human lifespan, the burden of chronic metabolic disease increasingly impacts the quality of life of almost two billion people worldwide. It is now imperative that we recognize metabolic disease as a pandemic and urgently prioritize preventive measures to halt its expansion.

Maternal methyl donor supplementation: A potential therapy for metabolic disorder in offspring.

The prevalences of diabetes mellitus and obesity are increasing yearly and has become a serious social burden. In addition to genetic factors, environmental factors in early life development are critical in influencing the prevalence of metabolic disorders in offspring. A growing body of evidence suggests the critical role of early methyl donor intervention in offspring health. Emerging studies have shown that methyl donors can influence offspring metabolism through epigenetic modifications and changing metabolism-related genes. In this review, we focus on the role of folic acid, betaine, vitamin B12, methionine, and choline in protecting against metabolic disorders in offspring. To address the current evidence on the potential role of maternal methyl donors, we summarize clinical studies as well as experimental animal models that support the impact of maternal methyl donors on offspring metabolism and discuss the mechanisms of action that may bring about these positive effects. Given the worldwide prevalence of metabolic disorders, these findings could be utilized in clinical practice, in which methyl donor supplementation in the early life years may reverse metabolic disorders in offspring and block the harmful intergenerational effect.

Gestational Diabetes and Long-Term Cardiometabolic Health.

This JAMA Insights discusses adverse long-term effects of gestational diabetes on the pregnant individual and the exposed fetus.

Intermittent Fasting and Physical Exercise for Preventing Metabolic Disorders through Interaction with Gut Microbiota: A Review.

Metabolic disorders entail both health risks and economic burdens to our society. A considerable part of the cause of metabolic disorders is mediated by the gut microbiota. The gut microbial structure and function are susceptible to dietary patterns and host physiological activities. A sedentary lifestyle accompanied by unhealthy eating habits propels the release of harmful metabolites, which impair the intestinal barrier, thereby triggering a constant change in the immune system and biochemical signals. Noteworthy, healthy dietary interventions, such as intermittent fasting, coupled with regular physical exercise can improve several metabolic and inflammatory parameters, resulting in stronger beneficial actions for metabolic health. In this review, the current progress on how gut microbiota may link to the mechanistic basis of common metabolic disorders was discussed. We also highlight the independent and synergistic effects of fasting and exercise interventions on metabolic health and provide perspectives for preventing metabolic disorders.

Physical Exercise and Diet: Regulation of Gut Microbiota to Prevent and Treat Metabolic Disorders to Maintain Health.

Each person's body is host to a large number and variety of gut microbiota, which has been described as the second genome and plays an important role in the body's metabolic process and is closely related to health. It is common knowledge that proper physical activity and the right diet structure can keep us healthy, and in recent years, researchers have found that this boost to health may be related to the gut microbiota. Past studies have reported that physical activity and diet can modulate the compositional structure of the gut microbiota and further influence the production of key metabolites of the gut microbiota, which can be an effective way to improve body metabolism and prevent and treat related metabolic diseases. In this review, we outline the role of physical activity and diet in regulating gut microbiota and the key role that gut microbiota plays in improving metabolic disorders. In addition, we highlight the regulation of gut microbiota through appropriate physical exercise and diet to improve body metabolism and prevent metabolic diseases, aiming to promote public health and provide a new approach to treating such diseases.

Ablation of miRNA-22 protects against obesity-induced adipocyte senescence and ameliorates metabolic disorders in middle-aged mice.

High-fat diet (HFD) promotes obesity-related metabolic complications by activating cellular senescence in white adipose tissue (WAT). Growing evidence supports the importance of microRNA-22 (miR-22) in metabolic disorders and cellular senescence. Recently, we showed that miR-22 deletion attenuates obesity-related metabolic abnormalities. However, whether miR-22 mediates HFD-induced cellular senescence of WAT remains unknown. Here, we uncovered that obese mice displayed increased pri-miR-22 levels and cellular senescence in WAT. However, miR-22 ablation protected mice against HFD-induced WAT senescence. In addition, in vitro studies showed that miR-22 deletion prevented preadipocyte senescence in response to Doxorubicin (Doxo). Loss-of-function studies in vitro and in vivo revealed that miR-22 increases H2ax mRNA and γH2ax levels in preadipocytes and WAT without inducing DNA damage. Intriguingly, miR-22 ablation prevented HFD-induced increase in γH2ax levels and DNA damage in WAT. Similarly, miR-22 deletion prevented Doxo-induced increase in γH2ax levels in preadipocytes. Adipose miR-22 levels were enhanced in middle-aged mice fed a HFD than those found in young mice. Furthermore, miR-22 deletion attenuated fat mass gain and glucose imbalance induced by HFD in middle-aged mice. Overall, our findings indicate that miR-22 is a key regulator of obesity-induced WAT senescence and metabolic disorders in middle-aged mice.

The effect of Xuezhikang capsule on gene expression profile in brown adipose tissue of obese spontaneously hypertensive rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Obesity is a critical threat to global health, and brown adipose tissue (BAT) is a potential target for the treatment of obesity and comorbidities. Xuezhikang Capsule (XZK), an extract of red yeast rice, has remarkable clinical efficacy and is widely used for the treatment of hyperlipidemia and coronary heart disease. However, its modulatory effect on BAT remains unknown. AIM OF THIS STUDY: The aim of this study was to investigate the protective mechanism of XZK in the obese spontaneously hypertensive rat (SHR) model by evaluating the regulatory effect of XZK on the BAT gene profile through transcriptome sequencing. MATERIALS AND METHODS: The SHRs were randomly divided into four groups: the standard chow diet (STD) group, the STD supplemented with 126 mg/kg of XZK group, the high-fat diet (HFD) group, and the HFD supplemented with 126 mg/kg of XZK group. All SHRs were fed for 18 weeks. The metabolic phenotypes, including body weight, fat mass, oral glucose tolerance test (OGTT), and serum glucose and lipid levels, was evaluated, and hematoxylin and eosin staining (H&E) staining was performed to evaluate the adipose tissue histopathological phenotype. Transcriptome sequencing was performed to determine the mechanism by which XZK improves the metabolic phenotype and the expression of key differential expression genes was verified by real-time quantitative polymerase chain reaction (qRT-PCR). RESULTS: XZK inhibited HFD-induced weight gain and adipose tissue remodeling in SHRs and prevented hypertrophy of epididymal adipocytes and maintained the brown fat phenotype. XZK intervention also improved glucose and lipid metabolism in SHRs, as suggested by a reduction in serum triglyceride (TG), low-density cholesterol (LDL-C), and fasting blood glucose (FBG) levels as well as increasing in serum high-density cholesterol (HDL-C) levels. Transcriptome sequencing analysis confirmed the regulatory effect of XZK on the gene expression profile of BAT, and the expression patterns of 45 genes were reversed by the XZK intervention. Additionally, the results of the transcriptome analysis of 10 genes that are important for brown fat function were in line with the results of qRT-PCR. CONCLUSIONS: XZK protected SHRs from HFD-induced obesity, inhibited fat accumulation and improved glucolipid metabolism. Additionally, the protective effect of XZK on the overall metabolism of obese SHRs might partly be related to its regulatory effect on the BAT gene expression profile. These findings might provide novel therapeutic strategies for obesity-related metabolic diseases in traditional Chinese medicine (TCM).

Targeting the gut to prevent and counteract metabolic disorders and pathologies during aging.

Impairment of gut function is one of the explanatory mechanisms of health status decline in elderly population. These impairments involve a decline in gut digestive physiology, metabolism and immune status, and associated to that, changes in composition and function of the microbiota it harbors. Continuous deteriorations are generally associated with the development of systemic dysregulations and ultimately pathologies that can worsen the initial health status of individuals. All these alterations observed at the gut level can then constitute a wide range of potential targets for development of nutritional strategies that can impact gut tissue or associated microbiota pattern. This can be key, in a preventive manner, to limit gut functionality decline, or in a curative way to help maintaining optimum nutrients bioavailability in a context on increased requirements, as frequently observed in pathological situations. The aim of this review is to give an overview on the alterations that can occur in the gut during aging and lead to the development of altered function in other tissues and organs, ultimately leading to the development of pathologies. Subsequently is discussed how nutritional strategies that target gut tissue and gut microbiota can help to avoid or delay the occurrence of aging-related pathologies.

Boron-Containing Compounds for Prevention, Diagnosis, and Treatment of Human Metabolic Disorders.

The application of natural and synthetic boron-containing compounds (BCC) in biomedical field is expanding. BCC have effects in the metabolism of living organisms. Some boron-enriched supplements are marketed as they exert effects in the bone and skeletal muscle; but also, BCC are being reported as acting on the enzymes and transporters of membrane suggesting they could modify the carbohydrate metabolism linked to some pathologies of high global burden, as an example is diabetes mellitus. Also, some recent findings are showing effects of BCC on lipid metabolism. In this review, information regarding the effects and interaction of these compounds was compiled, as well as the potential application for treating human metabolic disorders is suggested.

Special Issue: Nutraceutical Approaches to Cardiovascular and Metabolic Diseases: Evidence and Opportunities.

The effective prevention and treatment of cardiovascular and metabolic diseases is a major task for health systems since these pathological conditions are still major causes of mortality, morbidity, and disability worldwide [...].

Tendencia de consejerías en actividad física y enfermedades cardiometabólicas en el Maule, Chile: estudio previo a pandemia por COVID-19 entre 2012 y 2019 / Trend in Physical Activity Counseling and Cardiometabolic Diseases in Maule, Chile: COVID-19 Pre-Pandemic Study between 2012 and 2019

BACKGROUND: Physical activity (PA) practice reduces the adverse effects of COVID-19. PA counseling promotes healthy lifestyles and prevents cardiometabolic diseases. AIM: To assess the trend in cases of PA counseling and the cardiometabolic disease between 2012 and 2019 (before COVID-19) in a southern Chilean region. MATERIAL AND METHODS: Records of Maule Region Health Service for 731.163 men, and 829.097 women aged < 10 to ≥ 65 years were analyzed. The average annual percentage change (AAPC) during the study period and the annual percentage change (APC) during intermediate periods, were calculated. RESULTS: There was a significant decrease in PA counseling in women in the study period (AAPC: −13.6%). In the 2012-2017 period a significant decrease in counseling for total, men and women were observed (APC: −18.1, −16.5 and −19.1%, respectively). Obesity increased significantly in total, men and women in the 2012-2019 period (AAPC: 10.1, 8.5 and 10.7%, respectively). The same trend was observed for hypertension (AAPC: 8.1, 8.5 and 7.6% respectively) and elevated blood glucose (AAPC: 10, 11.5 and 9.6%, respectively). CONCLUSIONS: In the study period PA counseling decreased along with an increase in obesity, hypertension and high blood glucose. Increasing PA counseling is a mainstay in the prevention of cardiometabolic diseases and probably to prevent contagion and complement the treatment of COVID-19.

Combined Physical Exercise and Diet: Regulation of Gut Microbiota to Prevent and Treat of Metabolic Disease: A Review.

BACKGROUND: Unhealthy diet and sedentary lifestyle have contributed to the rising incidence of metabolic diseases, which is also accompanied by the shifts of gut microbiota architecture. The gut microbiota is a complicated and volatile ecosystem and can be regulated by diet and physical exercise. Extensive research suggests that diet alongside physical exercise interventions exert beneficial effects on metabolic diseases by regulating gut microbiota, involving in the changes of the energy metabolism, immune regulation, and the microbial-derived metabolites. OBJECTIVE: In this review, we present the latest evidence in the modulating role of diet and physical exercise in the gut microbiota and its relevance to metabolic diseases. We also summarize the research from animal and human studies on improving metabolic diseases through diet-plus-exercise interventions, and new targeted therapies that might provide a better understanding of the potential mechanisms. METHODS: A systematic and comprehensive literature search was performed in PubMed/Medline and Web of Science in October 2022. The key terms used in the searches included "combined physical exercise and diet", "physical exercise, diet and gut microbiota", "physical exercise, diet and metabolic diseases" and "physical exercise, diet, gut microbiota and metabolic diseases". CONCLUSIONS: Combined physical exercise and diet offer a more efficient approach for preventing metabolic diseases via the modification of gut microbiota, abating the burden related to longevity.

The Role of Epigenetic Regulator SIRT1 in Balancing the Homeostasis and Preventing the Formation of Specific "Soil" of Metabolic Disorders and Related Cancers.

SIRT1 was discovered in 1979 but growing interest in this protein occurred only 20 years later when its overexpression was reported to prolong the lifespan of yeast. Since then, several studies have shown the benefits of its increased expression in preventing or delaying of many diseases. SIRT1, as a histone deacetylase, is an epigenetic regulator but it has wide range of non-histone targets which are involved in metabolism, energy sensing pathways, circadian machinery and in inflammatory regulation. Disturbances in these interconnected processes cause different diseases, however it seems they have common roots in unbalanced inflammatory processes and lower level or inactivation of SIRT1. SIRT1 inactivation was implicated in coronavirus disease (COVID-19) severity as well and its low level counted as a predictor of uncontrolled COVID-19. Several other diseases such as metabolic disease, obesity, diabetes, Alzheimer's disease, cardiovascular disease or depression are related to chronic inflammation and similarly show decreased SIRT1 level. It has recently been known that SIRT1 is inducible by calorie restriction/proper diet, physical activity and appropriate emotional state. Indeed, a healthier metabolic state belongs to higher level of SIRT1 expression. These suggest that appropriate lifestyle as non-pharmacological treatment may be a beneficial tool in the prevention of inflammation or metabolic disturbance-related diseases as well as could be a part of the complementary therapy in medical practice to reach better therapeutic response and quality of life. We aimed in this review to link the beneficial effect of SIRT1 with those diseases, where its level decreased. Moreover, we aimed to collect evidences of interventions or treatments, which increase SIRT1 expression and thus, open the possibility to use them as preventive or complementary therapies in medical practice.

Dietary sugar lowers immunity and microbiota that protect against metabolic disease.

Diet influences intestinal microbiota, inflammation, and metabolism. Kawano et al. show that dietary sugar engaged upper gut innate lymphoid cells to replace segmented filamentous bacteria with a pathobiont. Added sugar worsened early metabolic disease by lowering protective Th17 immunity, thereby promoting intestinal lipid absorption and obesity in high-fat-diet-fed mice.

Polyunsaturated fatty acids and metabolic health: novel insights.

PURPOSE OF REVIEW: This review aims to discuss the potential roles of omega-3 (ω-3) and omega-6 (ω-6) polyunsaturated fatty acids (PUFAs) in the prevention and treatment of metabolic diseases, to provide the latest evidence from epidemiological and clinical studies, and to highlight novel insights into this field. RECENT FINDINGS: Higher dietary or circulating ω-3 PUFA levels are related to a lower risk of metabolic syndrome. Novel findings in obesity indicate higher proportions of ω-6 and ω-3 PUFAs, a modulated oxylipin profile and an altered transcriptome in subcutaneous white adipose tissue, that seem resistant to the effects of ω-3 PUFAs compared with what occurs in normal weight individuals. ω-3 PUFAs may improve the blood lipid profile and glycemic outcomes in patients with type 2 diabetes mellitus and reduce liver fat in nonalcoholic fatty liver disease (NAFLD); the findings of several recent meta-analyses support these effects. Genetic background affects inter-individual variability in the insulin sensitivity response to ω-3 PUFA supplementation. ω-3 PUFAs have prebiotic effects, altering the gut microbiota. SUMMARY: Although evidence for health benefits of ω-3 PUFAs is strong, recent findings suggest a more personalized approach to ω-3 PUFA intake for individuals at high risk for metabolic diseases.

Time for better time-restricted eating trials to lessen the burden of metabolic diseases.

Optimizing the quality, quantity, and timing of nutrition holds immense potential to improve health and prevent disease. The results of a recent randomized controlled trial1 have been widely misrepresented with the incorrect interpretation that optimizing the timing of food intake imparts no health benefits.