Overview of the therapeutic efficacy of marine fish oil in managing obesity and associated metabolic disorders.

In the present scenario, obesity is a challenging health problem and its prevalence along with comorbidities are on the rise around the world. Ingestion of fish becomes trendy in daily meals. Recent research has shown that marine fish oil (FO) (found in tuna, sardines, and mackerel) may offer an alternative method for reducing obesity and problems associated with it. Marine FO rich in long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA) and long-chain omega-6 polyunsaturated fatty acids (LC n-6 PUFA) plays an important role in reducing abnormalities associated with the metabolic syndrome and has a variety of disease-fighting properties, including cardioprotective activity, anti-atherosclerotic, anti-obesity, anti-cancer, anti-inflammatory activity. Studies in rodents and humans have indicated that LC n-3 PUFA potentially elicit a number of effects which might be useful for reducing obesity, including suppression of appetite, improvements in circulation, enhanced fat oxidation, energy expenditure, and reduced fat deposition. This review discusses the interplay between inflammation and obesity, and their subsequent regulation via the beneficial role of marine FO, suggesting an alternative dietary strategy to ameliorate obesity and obesity-associated chronic diseases.

Continuous glucose monitoring in patients with inherited metabolic disorders at risk for Hypoglycemia and Nutritional implications.

Managing Inherited Metabolic Disorders (IMDs) at risk for hypoglycemia, such as Glycogen Storage Diseases (GSDs), Hereditary Fructose Metabolism Disorders (HFMDs) and Congenital Hyperinsulinism (CH), poses challenges in dietary treatments and blood glucose monitoring. The effectiveness of Continuous Glucose Monitoring (CGM) remains a subject of ongoing debate, with IMD guidelines maintaining caution. Therefore, a systematic evaluation is needed to understand the potential benefits of CGM during dietary interventions. A systematic literature review was conducted in PubMed according to the PICOS model and PRISMA recommendations on studies published from January 01, 2003, up to October 15, 2023 (PROSPERO CRD42024497744). The risk of bias was assessed using NIH Quality Assessment Tools. Twenty-four studies in GSDs (n = 13), CH (n = 10), and HFMDs (n = 1) were analyzed. In GSDs, Real-time CGM (Rt-CGM) was associated with metabolic benefits during nutritional interventions, proving to be an accurate system for hypoglycemia detection although with some concerns about reliability. Rt-CGM in CH, primarily involving children, also showed potential benefits for glycemic control and metabolic stability with acceptable accuracy, although its use during dietary changes was limited. Few experiences on Flash Glucose Monitoring (FGM) were reported, with some concerns about reliability. Overall, the studies analyzed presented different designs, and their quality was predominantly fair or poor. Heterogeneity and limited consensus on reliability and glycemic targets underscore the need for prospective studies and future recommendations for the use of CGM in optimizing nutritional status and providing personalized dietary education in individuals with IMDs prone to hypoglycemia.

Recent advances in the potential of Phyllanthus emblica L. and its related foods for combating metabolic diseases through methylglyoxal trapping.

Methylglyoxal (MG) serves as the primary precursor for the nonenzymatic glycation of proteins and DNA, leading to advanced glycation end products (AGEs). Regular intake of dietary MG is strongly correlated with low-grade inflammation, potentially accelerating the pathogenesis of metabolic diseases, including obesity, diabetes, cancers, liver diseases, Alzheimer's disease, cardiovascular diseases, aging, and bone loss. Although pharmaceutical agents (pimagedine and candesartan) have been developed to inhibit MG formation, they often come with serious side effects (nausea, diarrhea, headache, gastrointestinal disturbance, symptomatic hypotension, abnormal renal and liver function tests, development of antinuclear antibody, pernicious-like anemia, and hyperkalemia), highlighting the need for an efficient and safe approach to scavenging MG. Phyllanthus emblica Linn fruit, a nutritious edible fruit, and medicinal plant contains over 300 bioactive compounds. Among twenty-three herbals, 100 µg/mL of the aqueous extract of Phyllanthus emblica fruit (APF) exhibits the highest potency in trapping MG, achieving an 87.3 % reduction under d-fructose induced BSA-AGEs formation. However, there are few reports detailing APF and its related foods' specific impact on disease prevention through MG trapping. This review summarizes the mechanisms through which MG is linked to the development of metabolic diseases and provides several strategies for reducing MG levels using APF and its bioactive compounds. The potential antiglycation properties of APF may offer new applications in the food industry and pharmacological research.

The use of capsicum oleoresin microparticles to mitigate hepatic damage and metabolic disorders induced by obesity.

Capsicum oleoresin has potential health benefits, particularly against obesity markers. Due to its high pungency, few studies have been done to explore the intake of this ingredient. The objective of this study was to use the Capsicum oleoresin (CO) microencapsulated into a high-fat diet to evaluate its metabolic effect on mice. Two formulation containing 15 % solids were prepared: the first (F1) with 5% CO and 95% emulsifier, and the second (F2) with 2.5% corn oil, 2.5% CO, and 95% emulsifier. These formulation were atomized in a spray dryer. Ultra-Performance Liquid Chromatography determined the capsaicin content for both formulations. Mice were divided into two groups: lean control (normocaloric AIN diet, n = 10) and high fat (HF diet: hypercaloric, n = 30), which were subdivided into three subgroups: HF control diet (n = 10); diet F1: HF + 20 % CO oleoresin microparticles (n = 10); and diet F2: HF + 20 % CO microparticles containing corn oil (n = 10). The animals treated with the microparticles showed lower glucose levels than the HF control. Mice fed with HF-containing CO microparticles had cholesterol blood levels similar to that of the lean group and lower (<100 mg/dL) than that of the HF control group (150 mg/dL). Capsicum oleoresin microparticles added to high-fat diets promoted lower weight gain and protected the liver against hepatic steatosis. Leptin levels for mice fed with HF diet plus CO microparticles averaged between 2 and 5 ng/ml, whereas the fat control group developed leptin resistance. Capsicum microparticles evidenced a protective effect against dyslipidemia compared to the fat control group, which suggests their use as a potential ingredient for the control of obesity.

Protective effects of puerarin on metabolic diseases: Emphasis on the therapeutical effects and the underlying molecular mechanisms.

Metabolic diseases (MetD) such as diabetes mellitus, obesity, and hyperlipidemia have become global health challenges. As a naturally occurring plant component, puerarin has been verified to possess a wide range of pharmacological effects including lowering blood glucose, improving insulin resistance, and regulating lipid metabolism, which has attracted extensive attention in recent years, and its potential in the treatment of MetD has been highly acclaimed. In addition, puerarin has exhibited antioxidant, anti-inflammatory, and cardiovascular protective effects, which are of great significance in the prevention and treatment of MetD. This article comprehensively summarizes the research progress of puerarin in the treatment of MetD and explores its pharmacological mechanisms, clinical applications, and future perspectives. More importantly, this review provided a list of the involved molecular mechanims in treating MetD of puerarin. Taking into account these conclusions, it may provide a strong foundation for the optimized use of puerarin in the treatment of patients suffering from MetD.

Use of Guazuma ulmifolia Lam. Stem Bark Extracts to Prevent High-Fat Diet Induced Metabolic Disorders in Mice.

This study aimed to evaluate the effects of supplementation with ethanolic and aqueous extracts from the bark of the stem of Guazuma ulmifolia in mice submitted to a high-fat diet as well as to evaluate the chemical composition of these extracts. The chemical composition and antioxidant potential was evaluated in aqueous and ethanolic extracts of the stem bark. The in vivo test consisted of evaluating the effects of the aqueous and ethanolic extracts of the stem bark on C57BL/6 mice receiving a high-fat diet. The animals were evaluated for weight gain, feed consumption, visceral adiposity, serum, and inflammatory and hormonal parameters. The results of the chemical analyses corroborate those obtained by the literature, which reported gallocatechin, epigallocatechin and epigallocatechin gallate. Compared with the ethanolic extract, the aqueous extract showed greater antioxidant capacity. Both extracts resulted in lower feed consumption in the animals, but they did not influence weight gain or visceral adiposity and resulted in varied changes in the lipid profile. In addition, they did not influence glucose tolerance, insulin sensitivity, or fasting blood glucose. Furthermore, the leptin levels increased, which may have contributed to satiety, but this was shown to have a negative impact on other inflammatory and hormonal parameters. Therefore, under the conditions of this study, the biologically active compounds present in the plant species Guazuma ulmifolia were not able to contribute to the treatment of metabolic changes related to the consumption of a high-fat diet.

Akkermansia muciniphila: A promising probiotic against inflammation and metabolic disorders.

Metabolic disease is a worldwide epidemic that has become a public health problem. Gut microbiota is considered to be one of the important factors that maintain human health by regulating host metabolism. As an abundant bacterium in the host gut, A. muciniphila regulates metabolic and immune functions, and protects gut health. Multiple studies have indicated that alterations in the abundance of A. muciniphila are associated with various diseases, including intestinal inflammatory diseases, obesity, type 2 diabetes mellitus, and even parasitic diseases. Beneficial effects were observed not only in live A. muciniphila, but also in pasteurized A. muciniphila, A. muciniphila-derived extracellular vesicles, outer membrane, and secreted proteins. Although numerous studies have only proven the simple correlation between multiple diseases and A. muciniphila, an increasing number of studies in animal models and preclinical models have demonstrated that the beneficial impacts shifted from correlations to in-depth mechanisms. In this review, we provide a comprehensive view of the beneficial effects of A. muciniphila on different diseases and summarize the potential mechanisms of action of A. muciniphila in the treatment of diseases. We provide a comprehensive understanding of A. muciniphila for improving host health and discuss the perspectives of A. muciniphila in the future studies.

Rising to the challenge of cardio-renal-metabolic disease in the 21st century: Translating evidence into best clinical practice to prevent and manage atherosclerosis.

Rising rates of obesity-associated cardiometabolic disorders allied to ageing populations are driving increases in cardiovascular morbidity and mortality. These adverse trends present challenges for healthcare systems that are struggling to prevent and manage the burgeoning cardiometabolic nexus of multiple long-term conditions. While potent new medications and non-pharmacological interventions have ushered in a promising new therapeutic era, translating clinical trial data to real-world clinical practice is often suboptimal. Postgraduate training and narrowly focused clinical specialisations reflect the traditional siloed approach to managing cardiovascular-metabolic disease that appears increasingly outmoded in the 21st century. It is our contention that greater inter-disciplinary collaboration allied to increased awareness of the continuum of cardiometabolic disease should enable clinicians to address this global public health threat more effectively. With this aim in mind, we have established an International Cardiometabolic Working Group. It is our hope to stimulate the interest of clinicians and clinical researchers across a range of medical specialties who share the vision of better care for people living with cardiometabolic diseases.

Exercise as a tool to mitigate metabolic disease.

Metabolic diseases, notably obesity and type 2 diabetes (T2D), have reached alarming proportions and constitute a significant global health challenge, emphasizing the urgent need for effective preventive and therapeutic strategies. In contrast, exercise training emerges as a potent intervention, exerting numerous positive effects on metabolic health through adaptations to the metabolic tissues. Here, we reviewed the major features of our current understanding with respect to the intricate interplay between metabolic diseases and key metabolic tissues, including adipose tissue, skeletal muscle, and liver, describing some of the main underlying mechanisms driving pathogenesis, as well as the role of exercise to combat and treat obesity and metabolic disease.

Recent advances on cyanidin-3-O-glucoside in preventing obesity-related metabolic disorders: A comprehensive review.

Anthocyanins, found in various pigmented plants as secondary metabolites, represent a class of dietary polyphenols known for their bioactive properties, demonstrating health-promoting effects against several chronic diseases. Among these, cyanidin-3-O-glucoside (C3G) is one of the most prevalent types of anthocyanins. Upon consumption, C3G undergoes phases I and II metabolism by oral epithelial cells, absorption in the gastric epithelium, and gut transformation (phase II & microbial metabolism), with limited amounts reaching the bloodstream. Obesity, characterized by excessive body fat accumulation, is a global health concern associated with heightened risks of disability, illness, and mortality. This comprehensive review delves into the biodegradation and absorption dynamics of C3G within the gastrointestinal tract. It meticulously examines the latest research findings, drawn from in vitro and in vivo models, presenting evidence underlining C3G's bioactivity. Notably, C3G has demonstrated significant efficacy in combating obesity, by regulating lipid metabolism, specifically decreasing lipid synthesis, increasing fatty acid oxidation, and reducing lipid accumulation. Additionally, C3G enhances energy homeostasis by boosting energy expenditure, promoting the activity of brown adipose tissue, and stimulating mitochondrial biogenesis. Furthermore, C3G shows potential in managing various prevalent obesity-related conditions. These include cardiovascular diseases (CVD) and hypertension through the suppression of reactive oxygen species (ROS) production, enhancement of endogenous antioxidant enzyme levels, and inhibition of the nuclear factor-kappa B (NF-κB) signaling pathway and by exercising its cardioprotective and vascular effects by decreasing pulmonary artery thickness and systolic pressure which enhances vascular relaxation and angiogenesis. Type 2 diabetes mellitus (T2DM) and insulin resistance (IR) are also managed by reducing gluconeogenesis via AMPK pathway activation, promoting autophagy, protecting pancreatic ß-cells from oxidative stress and enhancing glucose-stimulated insulin secretion. Additionally, C3G improves insulin sensitivity by upregulating GLUT-1 and GLUT-4 expression and regulating the PI3K/Akt pathway. C3G exhibits anti-inflammatory properties by inhibiting the NF-κB pathway, reducing pro-inflammatory cytokines, and shifting macrophage polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. C3G demonstrates antioxidative effects by enhancing the expression of antioxidant enzymes, reducing ROS production, and activating the Nrf2/AMPK signaling pathway. Moreover, these mechanisms also contribute to attenuating inflammatory bowel disease and regulating gut microbiota by decreasing Firmicutes and increasing Bacteroidetes abundance, restoring colon length, and reducing levels of inflammatory cytokines. The therapeutic potential of C3G extends beyond metabolic disorders; it has also been found effective in managing specific cancer types and neurodegenerative disorders. The findings of this research can provide an important reference for future investigations that seek to improve human health through the use of naturally occurring bioactive compounds.

Effects of high-quality protein supplementation on cardiovascular risk factors in individuals with metabolic diseases: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Uncertainties still existed about the effect of high-quality protein supplementation on cardiovascular disease (CVD) risk factors, although high-quality proteins such as soy and milk proteins have proposed to be beneficial for cardiometabolic health. METHODS: A systematic search in PubMed, Web of Science, Cochrane Library, Scopus, and Embase was conducted to quantify the impact of high-quality protein on CVD risk factors. RESULTS: 63 RCTs on 4 types of high-quality protein including soy protein, milk protein, whey, and casein were evaluated. Soy protein supplementation decreased systolic blood pressure (SBP, -1.42 [-2.68, -0.17] mmHg), total cholesterol (TC, -0.18 [-0.30, -0.07] mmol/L), and low-density lipoprotein cholesterol (LDL-C, -0.16 [-0.27, -0.05] mmol/L). Milk protein supplementation decreased SBP (-2.30 [-3.45, -1.15] mmHg) and total cholesterol (-0.27 [-0.51, -0.03] mmol/L). Whey supplementation decreased SBP (-2.20 [-3.89, -0.51] mmHg), diastolic blood pressure (DBP, -1.07 [-1.98, -0.16] mmHg), triglycerides (-0.10 [-0.17, -0.03] mmol/L), TC (-0.18 [-0.35, -0.01] mmol/L), LDL-C (-0.09 [-0.16, -0.01] mmol/L) and fasting blood insulin (FBI, -2.02 [-3.75, -0.29] pmol/L). Casein supplementation decreased SBP (-4.10 [-8.05, -0.14] mmHg). In the pooled analysis of four high-quality proteins, differential effects were seen in individuals with different health status. In hypertensive individuals, high-quality proteins decreased both SBP (-2.69 [-3.50, -1.87] mmHg) and DBP (-1.34 [-2.09, -0.60] mmHg). In overweight/obese individuals, high-quality proteins improved SBP (-1.40 [-2.22, -0.59] mmHg), DBP (-2.59 [-3.20, -1.98] mmHg), triglycerides (-0.09 [-0.15, -0.02] mmol/L), TC (-0.14 [-0.22, -0.05] mmol/L), LDL-C (-0.12 [-0.16, -0.07] mmol/L), and HDL-C levels (0.02 [0.01, 0.04] mmol/L). According to the benefits on CVD risks factors, whey ranked top for improving cardiometabolic health in hypertensive or overweight/obese individuals. CONCLUSION: Our study supports a beneficial role of high-quality protein supplementation to reduce CVD risk factors. Further studies are still warranted to investigate the effects of different high-quality proteins on CVD risks in individuals with cardiometabolic disorders.

The role of tetrahydrocurcumin in disease prevention and treatment.

In recent decades, natural compounds derived from herbal medicine or dietary sources have played important roles in prevention and treatment of various diseases and have attracted more and more attention. Curcumin, extracted from the Curcumae Longae Rhizoma and widely used as food spice and coloring agent, has been proven to possess high pharmacological value. However, the pharmacological application of curcumin is limited due to its poor systemic bioavailability. As a major active metabolite of curcumin, tetrahydrocurcumin (THC) has higher bioavailability and stability than curcumin. Increasing evidence confirmed that THC had a wide range of biological activities and significant treatment effects on diseases. In this paper, we reviewed the research progress on the biological activities and therapeutic potential of THC on different diseases such as neurological disorders, metabolic syndromes, cancers, and inflammatory diseases. The extensive pharmacological effects of THC involve the modulation of various signaling transduction pathways including MAPK, JAK/STAT, NF-κB, Nrf2, PI3K/Akt/mTOR, AMPK, Wnt/ß-catenin. In addition, the pharmacokinetics, drug combination and toxicology of THC were discussed, thus providing scientific basis for the safe application of THC and the development of its dietary supplements and drugs.

[Guidelines for the prevention and treatment of metabolic dysfunction-associated (non-alcoholic) fatty liver disease (Version 2024)].

The Chinese Society of Hepatology of the Chinese Medical Association invited relevant experts to revise and update the Guideline of Prevention and Treatment of Nonalcoholic Fatty Liver Disease (2018Version) and renamed it as (Version 2024) Guideline for the Prevention and Treatment of Metabolic Dysfunction-associated (non-alcoholic) Fatty Liver Disease. Herein, the guiding recommendations on clinical issues such as screening and monitoring, diagnosis and evaluation, treatment and follow-up of metabolic dysfunction-associated fatty liver disease are put forward.

The adiponectin-derived peptide ALY688 protects against the development of metabolic dysfunction-associated steatohepatitis.

Metabolic dysfunction-associated steatohepatitis (MASH) is the severe form of non-alcoholic fatty liver disease which has a high potential to progress to cirrhosis and hepatocellular carcinoma, yet adequate effective therapies are lacking. Hypoadiponectinemia is causally involved in the pathogenesis of MASH. This study investigated the pharmacological effects of adiponectin replacement therapy with the adiponectin-derived peptide ALY688 (ALY688-SR) in a mouse model of MASH. Human induced pluripotent stem (iPS) cell-derived hepatocytes were used to test cytotoxicity and signaling of unmodified ALY688 in vitro. High-fat diet with low methionine and no added choline (CDAHF) was used to induce MASH and test the effects of ALY688-SR in vivo. Histological MASH activity score (NAS) and fibrosis score were determined to assess the effect of ALY688-SR. Transcriptional characterization of mice through RNA sequencing was performed to indicate potential molecular mechanisms involved. In cultured hepatocytes, ALY688 efficiently induced adiponectin-like signaling, including the AMP-activated protein kinase and p38 mitogen-activated protein kinase pathways, and did not elicit cytotoxicity. Administration of ALY688-SR in mice did not influence body weight but significantly ameliorated CDAHF-induced hepatic steatosis, inflammation, and fibrosis, therefore effectively preventing the development and progression of MASH. Mechanistically, ALY688-SR treatment markedly induced hepatic expression of genes involved in fatty acid oxidation, whereas it significantly suppressed the expression of pro-inflammatory and pro-fibrotic genes as demonstrated by transcriptomic analysis. ALY688-SR may represent an effective approach in MASH treatment. Its mode of action involves inhibition of hepatic steatosis, inflammation, and fibrosis, possibly via canonical adiponectin-mediated signaling.

Usefulness of Opuntia spp. on the Management of Obesity and Its Metabolic Co-Morbidities.

The plants of the Opuntia genus mainly grow in arid and semi-arid climates. Although the highest variety of wild species is found in Mexico, Opuntia spp. is widely distributed throughout the world. Extracts of these cacti have been described as important sources of bioactive substances that can have beneficial properties for the prevention and treatment of certain metabolic disorders. The objective of this review is to summarise the presently available knowledge regarding Opuntia ficus-indica (nopal or prickly pear), and some other species (O. streptacantha and O. robusta) on obesity and several metabolic complications. Current data show that Opuntia ficus-indica products used in preclinical studies have a significant capacity to prevent, at least partially, obesity and certain derived co-morbidities. On this subject, the potential beneficial effects of Opuntia are related to a reduction in oxidative stress and inflammation markers. Nevertheless, clinical studies have evidenced that the effects are highly contingent upon the experimental design. Moreover, the bioactive compound composition of nopal extracts has not been reported. As a result, there is a lack of information to elucidate the mechanisms of action responsible for the observed effects. Accordingly, further studies are needed to demonstrate whether Opuntia products can represent an effective tool to prevent and/or manage body weight and some metabolic disorders.

Rab18 maintains homeostasis of subcutaneous adipose tissue to prevent obesity-induced metabolic disorders.

Metabolically healthy obesity refers to obese individuals who do not develop metabolic disorders. These people store fat in subcutaneous adipose tissue (SAT) rather than in visceral adipose tissue (VAT). However, the molecules participating in this specific scenario remain elusive. Rab18, a lipid droplet (LD)-associated protein, mediates the contact between the endoplasmic reticulum (ER) and LDs to facilitate LD growth and maturation. In the present study, we show that the protein level of Rab18 is specifically upregulated in the SAT of obese people and mice. Rab18 adipocyte-specific knockout (Rab18 AKO) mice had a decreased volume ratio of SAT to VAT compared with wildtype mice. When subjected to high-fat diet (HFD), Rab18 AKO mice had increased ER stress and inflammation, reduced adiponectin, and decreased triacylglycerol (TAG) accumulation in SAT. In contrast, TAG accumulation in VAT, brown adipose tissue (BAT) or liver of Rab18 AKO mice had a moderate increase without ER stress stimulation. Rab18 AKO mice developed insulin resistance and systematic inflammation. Rab18 AKO mice maintained body temperature in response to acute and chronic cold induction with a thermogenic SAT, similar to the counterpart mice. Furthermore, Rab18-deficient 3T3-L1 adipocytes were more prone to palmitate-induced ER stress, indicating the involvement of Rab18 in alleviating lipid toxicity. Rab18 AKO mice provide a good animal model to investigate metabolic disorders such as impaired SAT. In conclusion, our studies reveal that Rab18 is a key and specific regulator that maintains the proper functions of SAT by alleviating lipid-induced ER stress.

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.

Pemafibrate and other triglyceride-lowering therapies to reduce risk of cardiovascular and metabolic disease.

PURPOSE OF REVIEW: Although high triglycerides are consistently associated with elevated risk of cardiovascular disease (CVD), therapies that reduce triglyceride levels have inconsistently translated into reduced CVD risk. RECENT FINDINGS: To date, three clinical trials have tested triglyceride-lowering therapies in patients with hypertriglyceridemia (HTG) and elevated risk of incident/recurrent CVD. In REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial), assignment to IPE, a highly purified eicosapentanoic acid (EPA), resulted in a 25% reduction in nonfatal myocardial infarction), nonfatal stroke, cardiovascular death, coronary revascularization and hospitalization for unstable angina. By contrast, the combination of EPA and docosahexanoic acid (DHA) carboxylic fatty acids used in the STRENGTH trial (Statin Residual Risk With Epanova in High Cardiovascular Risk Patients With Hypertriglyceridemia) failed to reduce CVD risk. Most recently, PROMINENT (Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients with Diabetes) also failed to demonstrate reduction in CVD events despite use of a potent triglyceride-lowering, fibric-acid derivative. However, improvement in HTG-associated metabolic complications (e.g. nonalcoholic fatty liver disease) was observed with pemafibrate as well as with another potent triglyceride-lowering therapy (i.e. pegozafermin). Moreover, trials are underway evaluating whether the most fatal metabolic complication of HTG, pancreatitis, may be reduced with highly potent triglyceride-lowering therapies (e.g. apolipoprotein C3 inhibitors). SUMMARY: Taken together, HTG is associated with increased risk of CVD and attendant adverse metabolic sequalae. To this end, a potentially promising and evidence-based landscape is emerging for treating a clinical phenotype that in the past has been insufficiently addressed.

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.

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.