Potential regulatory role of PGC-1α within the skeletal muscle during metabolic adaptations in response to high-fat diet feeding in animal models.

High-fat diet (HFD) feeding in rodents has become an essential tool to critically analyze and study the pathological effects of obesity, including mitochondrial dysfunction and insulin resistance. Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) regulates cellular energy metabolism to influence insulin sensitivity, beyond its active role in stimulating mitochondrial biogenesis to facilitate skeletal muscle adaptations in response to HFD feeding. Here, some of the major electronic databases like PubMed, Embase, and Web of Science were accessed to update and critically discuss information on the potential role of PGC-1α during metabolic adaptations within the skeletal muscle in response to HFD feeding in rodents. In fact, available evidence suggests that partial exposure to HFD feeding (potentially during the early stages of disease development) is associated with impaired metabolic adaptations within the skeletal muscle, including mitochondrial dysfunction and reduced insulin sensitivity. In terms of implicated molecular mechanisms, these negative effects are partially associated with reduced activity of PGC-1α, together with the phosphorylation of protein kinase B and altered expression of genes involving nuclear respiratory factor 1 and mitochondrial transcription factor A within the skeletal muscle. Notably, metabolic abnormalities observed with chronic exposure to HFD (likely during the late stages of disease development) may potentially occur independently of PGC-1α regulation within the muscle of rodents. Summarized evidence suggests the causal relationship between PGC-1α regulation and effective modulations of mitochondrial biogenesis and metabolic flexibility during the different stages of disease development. It further indicates that prominent interventions like caloric restriction and physical exercise may affect PGC-1α regulation during effective modulation of metabolic processes.

Evaluating the Therapeutic Potential of Curcumin and Synthetic Derivatives: A Computational Approach to Anti-Obesity Treatments.

Natural compounds such as curcumin, a polyphenolic compound derived from the rhizome of turmeric, have gathered remarkable scientific interest due to their diverse metabolic benefits including anti-obesity potential. However, curcumin faces challenges stemming from its unfavorable pharmacokinetic profile. To address this issue, synthetic curcumin derivatives aimed at enhancing the biological efficacy of curcumin have previously been developed. In silico modelling techniques have gained significant recognition in screening synthetic compounds as drug candidates. Therefore, the primary objective of this study was to assess the pharmacokinetic and pharmacodynamic characteristics of three synthetic derivatives of curcumin. This evaluation was conducted in comparison to curcumin, with a specific emphasis on examining their impact on adipogenesis, inflammation, and lipid metabolism as potential therapeutic targets of obesity mechanisms. In this study, predictive toxicity screening confirmed the safety of curcumin, with the curcumin derivatives demonstrating a safe profile based on their LD50 values. The synthetic curcumin derivative 1A8 exhibited inactivity across all selected toxicity endpoints. Furthermore, these compounds were deemed viable candidate drugs as they adhered to Lipinski's rules and exhibited favorable metabolic profiles. Molecular docking studies revealed that both curcumin and its synthetic derivatives exhibited favorable binding scores, whilst molecular dynamic simulations showed stable binding with peroxisome proliferator-activated receptor gamma (PPARγ), csyclooxygenase-2 (COX2), and fatty acid synthase (FAS) proteins. The binding free energy calculations indicated that curcumin displayed potential as a strong regulator of PPARγ (-60.2 ± 0.4 kcal/mol) and FAS (-37.9 ± 0.3 kcal/mol), whereas 1A8 demonstrated robust binding affinity with COX2 (-64.9 ± 0.2 kcal/mol). In conclusion, the results from this study suggest that the three synthetic curcumin derivatives have similar molecular interactions to curcumin with selected biological targets. However, in vitro and in vivo experimental studies are recommended to validate these findings.

Sulforaphane: A nutraceutical against diabetes-related complications.

There is an increasing interest in the use of nutraceuticals and plant-derived bioactive compounds from foods for their potential health benefits. For example, as a major active ingredient found from cruciferous vegetables like broccoli, there has been growing interest in understanding the therapeutic effects of sulforaphane against diverse metabolic complications. The past decade has seen an extensive growth in literature reporting on the potential health benefits of sulforaphane to neutralize pathological consequences of oxidative stress and inflammation, which may be essential in protecting against diabetes-related complications. In fact, preclinical evidence summarized within this review supports an active role of sulforaphane in activating nuclear factor erythroid 2-related factor 2 or effectively modulating AMP-activated protein kinase to protect against diabetic complications, including diabetic cardiomyopathy, diabetic neuropathy, diabetic nephropathy, as well as other metabolic complications involving non-alcoholic fatty liver disease and skeletal muscle insulin resistance. With clinical evidence suggesting that foods rich in sulforaphane like broccoli can improve the metabolic status and lower cardiovascular disease risk by reducing biomarkers of oxidative stress and inflammation in patients with type 2 diabetes. This information remains essential in determining the therapeutic value of sulforaphane or its potential use as a nutraceutical to manage diabetes and its related complications. Finally, this review discusses essential information on the bioavailability profile of sulforaphane, while also covering information on the pathological consequences of oxidative stress and inflammation that drive the development and progression of diabetes.

Therapeutic Effects of Curcumin Derivatives against Obesity and Associated Metabolic Complications: A Review of In Vitro and In Vivo Studies.

Obesity is a major cause of morbidity and mortality globally, increasing the risk for chronic diseases. Thus, the need to identify more effective anti-obesity agents has spurred significant interest in the health-promoting properties of natural compounds. Of these, curcumin, the most abundant and bioactive constituent of turmeric, possesses a variety of health benefits including anti-obesity effects. However, despite its anti-obesity potential, curcumin has demonstrated poor bioavailability, which limits its clinical applicability. Synthesizing curcumin derivatives, which are structurally modified analogs of curcumin, has been postulated to improve bioavailability while maintaining therapeutic efficacy. This review summarizes in vitro and in vivo studies that assessed the effects of curcumin derivatives against obesity and its associated metabolic complications. We identified eight synthetic curcumin derivatives that were shown to ameliorate obesity and metabolic dysfunction in diet-induced obese animal models, while five of these derivatives also attenuated obesity and associated metabolic complications in cell culture models. These curcumin derivatives modulated adipogenesis, lipid metabolism, insulin resistance, steatosis, lipotoxicity, inflammation, oxidative stress, endoplasmic reticulum stress, apoptosis, autophagy, fibrosis, and dyslipidemia to a greater extent than curcumin. In conclusion, the findings from this review show that compared to curcumin, synthetic curcumin derivatives present potential candidates for further development as therapeutic agents to modulate obesity and obesity-associated metabolic complications.

Anti-Obesity Effects of Metformin: A Scoping Review Evaluating the Feasibility of Brown Adipose Tissue as a Therapeutic Target.

Brown adipose tissue (BAT) is increasingly recognized as the major therapeutic target to promote energy expenditure and ameliorate diverse metabolic complications. There is a general interest in understanding the pleiotropic effects of metformin against metabolic complications. Major electronic databases and search engines such as PubMed/MEDLINE, Google Scholar, and the Cochrane library were used to retrieve and critically discuss evidence reporting on the impact of metformin on regulating BAT thermogenic activity to ameliorate complications linked with obesity. The summarized evidence suggests that metformin can reduce body weight, enhance insulin sensitivity, and improve glucose metabolism by promoting BAT thermogenic activity in preclinical models of obesity. Notably, this anti-diabetic agent can affect the expression of major thermogenic transcriptional factors such as uncoupling protein 1 (UCP1), nuclear respiratory factor 1 (NRF1), and peroxisome-proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α) to improve BAT mitochondrial function and promote energy expenditure. Interestingly, vital molecular markers involved in glucose metabolism and energy regulation such as AMP-activated protein kinase (AMPK) and fibroblast growth factor 21 (FGF21) are similarly upregulated by metformin treatment in preclinical models of obesity. The current review also discusses the clinical relevance of BAT and thermogenesis as therapeutic targets. This review explored critical components including effective dosage and appropriate intervention period, consistent with the beneficial effects of metformin against obesity-associated complications.

Pathological Role of Oxidative Stress in Aflatoxin-Induced Toxicity in Different Experimental Models and Protective Effect of Phytochemicals: A Review.

Aflatoxin B1 is a secondary metabolite with a potentially devastating effect in causing liver damage in broiler chickens, and this is mainly facilitated through the generation of oxidative stress and malonaldehyde build-up. In the past few years, significant progress has been made in controlling the invasion of aflatoxins. Phytochemicals are some of the commonly used molecules endowed with potential therapeutic effects to ameliorate aflatoxin, by inhibiting the production of reactive oxygen species and enhancing intracellular antioxidant enzymes. Experimental models involving cell cultures and broiler chickens exposed to aflatoxin or contaminated diet have been used to investigate the ameliorative effects of phytochemicals against aflatoxin toxicity. Electronic databases such as PubMed, Science Direct, and Google Scholar were used to identify relevant data sources. The retrieved information reported on the link between aflatoxin B1-included cytotoxicity and the ameliorative potential/role of phytochemicals in chickens. Importantly, retrieved data showed that phytochemicals may potentially protect against aflatoxin B1-induced cytotoxicity by ameliorating oxidative stress and enhancing intracellular antioxidants. Preclinical data indicate that activation of nuclear factor erythroid 2-related factor 2 (Nrf2), together with its downstream antioxidant genes, may be a potential therapeutic mechanism by which phytochemicals neutralize oxidative stress. This highlights the need for more research to determine whether phytochemicals can be considered a useful therapeutic intervention in controlling mycotoxins to improve broiler health and productivity.

Potential Benefits of Coffee Consumption on Improving Biomarkers of Oxidative Stress and Inflammation in Healthy Individuals and Those at Increased Risk of Cardiovascular Disease.

Cardiovascular diseases (CVDs) are considered the predominant cause of death globally. An abnormal increase in biomarkers of oxidative stress and inflammation are consistently linked with the development and even progression of metabolic diseases, including enhanced CVD risk. Coffee is considered one of the most consumed beverages in the world, while reviewed evidence regarding its capacity to modulate biomarkers of oxidative stress and inflammation remains limited. The current study made use of prominent electronic databases, including PubMed, Google Scholar, and Scopus to retrieve information from randomized controlled trials reporting on any association between coffee consumption and modulation of biomarkers of oxidative stress and inflammation in healthy individuals or those at increased risk of developing CVD. In fact, summarized evidence indicates that coffee consumption, mainly due to its abundant antioxidant properties, can reduce biomarkers of oxidative stress and inflammation, which can be essential in alleviating the CVD risk in healthy individuals. However, more evidence suggests that regular/prolonged use or long term (>4 weeks) consumption of coffee appeared to be more beneficial in comparison with short-term intake (<4 weeks). These positive effects are also observed in individuals already presenting with increased CVD risk, although such evidence is very limited. The current analysis of data highlights the importance of understanding how coffee consumption can be beneficial in strengthening intracellular antioxidants to alleviate pathological features of oxidative stress and inflammation to reduce CVD risk within the general population. Also covered within the review is essential information on the metabolism and bioavailability profile of coffee, especially caffeine as one of its major bioactive compounds.

Bioactive Properties, Bioavailability Profiles, and Clinical Evidence of the Potential Benefits of Black Pepper (Piper nigrum) and Red Pepper (Capsicum annum) against Diverse Metabolic Complications.

The consumption of food-derived products, including the regular intake of pepper, is increasingly evaluated for its potential benefits in protecting against diverse metabolic complications. The current study made use of prominent electronic databases including PubMed, Google Scholar, and Scopus to retrieve clinical evidence linking the intake of black and red pepper with the amelioration of metabolic complications. The findings summarize evidence supporting the beneficial effects of black pepper (Piper nigrum L.), including its active ingredient, piperine, in improving blood lipid profiles, including reducing circulating levels of total cholesterol, low-density lipoprotein cholesterol, and triglycerides in overweight and obese individuals. The intake of piperine was also linked with enhanced antioxidant and anti-inflammatory properties by increasing serum levels of superoxide dismutase while reducing those of malonaldehyde and C-reactive protein in individuals with metabolic syndrome. Evidence summarized in the current review also indicates that red pepper (Capsicum annum), together with its active ingredient, capsaicin, could promote energy expenditure, including limiting energy intake, which is likely to contribute to reduced fat mass in overweight and obese individuals. Emerging clinical evidence also indicates that pepper may be beneficial in alleviating complications linked with other chronic conditions, including osteoarthritis, oropharyngeal dysphagia, digestion, hemodialysis, and neuromuscular fatigue. Notably, the beneficial effects of pepper or its active ingredients appear to be more pronounced when used in combination with other bioactive compounds. The current review also covers essential information on the metabolism and bioavailability profiles of both pepper species and their main active ingredients, which are all necessary to understand their potential beneficial effects against metabolic diseases.

A systematic review exploring the significance of measuring epicardial fat thickness in correlation to B-type natriuretic peptide levels as prognostic and diagnostic markers in patients with or at risk of heart failure.

Emerging evidence suggests that epicardial fat thickness (EFT) may be a critical feature to understand cardiac health and determine the risk of heart failure. The current review critically assesses and discusses evidence on the efficiency of measuring EFT, in comparison to the well-known markers B-type natriuretic peptide (BNP) and its N-terminal fragment pro-B-type natriuretic peptide (NT-proBNP), as a prognostic and diagnostic approach in individuals with or at risk of heart failure. A systematic approach was undertaken to search major databases, PubMed, Scopus, Google Scholar and the Cochrane library to identify studies that quantified EFT and serum BNP/NT-proBNP levels in individuals with or at risk of heart failure. Twelve studies met the inclusion criteria and a total of 1983 participants were included in this systematic review. Evidence shows a clear association between increased EFT and elevated BNP/NT-proBNP levels in individuals with metabolic disease and suggests that both methods can be used for heart failure diagnosis and prognosis. However, due to the broad spectrum of challenges linked with measuring EFT, BNP/Pro-BNP is the predominant method used for heart failure diagnosis and prognosis in clinical practice. Nonetheless, measuring EFT provides a powerful and reproducible diagnostic tool for risk stratification and heart failure diagnosis and prognosis. Importantly, measuring EFT proves valuable to validate BNP/NT-proBNP levels to predict heart failure, especially due to its non-invasive nature.

Rutin ameliorates inflammation and improves metabolic function: A comprehensive analysis of scientific literature.

Chronic inflammation remains an essential complication in the pathogenesis and aggravation of metabolic diseases. There is a growing interest in the use of medicinal plants or food-derived bioactive compounds for their antioxidant and anti-inflammatory properties to improve metabolic function. For example, rutin, a flavonol derivative of quercetin that is found in several medicinal plants and food sources has displayed therapeutic benefits against diverse metabolic diseases. Here, we searched the major electronic databases and search engines such as PubMed/MEDLINE, Scopus and Google Scholar to systematically extract and critically discuss evidence reporting on the impact of rutin against metabolic diseases by affecting inflammation. In fact, available preclinical evidence suggests that rutin, through its strong antioxidant properties, can effectively ameliorate inflammation by reducing the levels of pro-inflammatory markers such as tumor necrosis factor-α, interleukin (IL)-6, cyclooxygenase-2, IL-1ß, as well as blocking nuclear factor kappa B (NF-κB)/mitogen-activated protein kinase (MAPK) activation to improve metabolic function. Notably, although clinical data on the impact of rutin on inflammation is limited, food-derived sources rich in this flavonol such as Fagopyrum tataricum, Coffea arabica and Aspalathus linearis (rooibos) have shown promise in improving metabolic function, in part by reducing markers of oxidative stress and inflammation. However, additional studies are still required to confirm the therapeutic properties of rutin in a clinical setting, including the enhancement of it low bioavailability profile.

Epigallocatechin gallate as a nutraceutical to potentially target the metabolic syndrome: novel insights into therapeutic effects beyond its antioxidant and anti-inflammatory properties.

Epigallocatechin gallate (EGCG) is one of the most abundant and powerful flavonoids contained in green tea. Because of the global increase in green tea consumption, there has been a general interest in understanding its health benefits, including its bioactive compounds like EGCG. Indeed, preclinical evidence already indicates that EGCG demonstrated a strong antioxidant and anti-inflammatory properties that could be essential in protecting against metabolic syndrome. The current review explores clinical evidence reporting on the beneficial effects of EGCG supplementation in obese subjects or patients with diverse metabolic complications that include type 2 diabetes and cardiovascular disease. The discussion incorporates the impact of different formulations of EGCG, as well as the effective doses and treatment duration. Importantly, besides highlighting the potential use of EGCG as a nutraceutical, the current review also discusses crucial evidence related to its pharmaceutical development as an agent to hinder metabolic diseases, including its bioavailability and metabolism profile, as well as its well-known biological properties.

Metformin and heart failure-related outcomes in patients with or without diabetes: a systematic review of randomized controlled trials.

Metformin is considered a safe anti-hyperglycemic drug for patients with type 2 diabetes (T2D); however, information on its impact on heart failure-related outcomes remains inconclusive. The current systematic review explored evidence from randomized clinical trials (RCTs) reporting on the impact of metformin in modulating heart failure-related markers in patients with or without T2D. Electronic databases such as MEDLINE, Cochrane Library, and EMBASE were searched for eligible studies. Included studies were those assessing the use of metformin as an intervention, and also containing the comparison group on placebo, and all articles had to report on measurable heart failure-related indices in individuals with or without T2D. The modified Downs and Black checklist was used to evaluate the risk of bias. Overall, nine studies met the inclusion criteria, enrolling a total of 2486 patients. Although summarized evidence showed that metformin did not affect left ventricular function, this antidiabetic drug could improve myocardial oxygen consumption concomitant to reducing prominent markers of heart failure such as n-terminal pro-brain natriuretic peptide and low-density lipoprotein levels, inconsistently between diabetic and nondiabetic patients. Effective modulation of some heart failure-related outcomes with metformin treatment was related to its beneficial effects in ameliorating insulin resistance and blocking pro-inflammatory markers such as the aging-associated cytokine CCL11 (C-C motif chemokine ligand 11). Overall, although such beneficial effects were observed with metformin treatment, additional RCTs are necessary to improve our understanding on its modulatory effects on heart failure-related outcomes especially in diabetic patients.

Adipokines as a therapeutic target by metformin to improve metabolic function: A systematic review of randomized controlled trials.

Metformin is a widely used glucose-lowering drug, although its impact on adipose tissue function remains elusive. Adipose tissue-derived molecules regulate diverse physiological mechanisms, including energy metabolism, insulin sensitization, and inflammatory response. Alternatively, it has remained relevant to understand the therapeutic regulation of adipokines in efforts to alleviate inflammation in conditions associated with the metabolic syndrome. The current qualitative analysis of available literature focused on randomized clinical trials (RCTs) assessing the association between administration of metformin and adipokine regulation in individuals with metabolic syndrome. The major electronic databases such as MEDLINE, Cochrane Library, Scopus, and EMBASE were searched for eligible RCTs. Overall, 13 RCTs met the inclusion criteria, with a total of 4605 participants. Patients with metabolic syndrome were characterized by a state of obesity, impaired glucose tolerance, insulin resistance, and type 2 diabetes. Cumulative evidence from these RCTs supported the blood glucose lowering effects of metformin, in addition to promoting weight loss, ameliorating insulin resistance, and reducing pro-inflammatory markers such as interleukin-6 and tumor necrosis factor-α in patients with metabolic syndrome. Importantly, these therapeutic effects are associated with the upregulation of adiponectin and suppression of leptin and resistin.

Rooibos Flavonoids, Aspalathin, Isoorientin, and Orientin Ameliorate Antimycin A-Induced Mitochondrial Dysfunction by Improving Mitochondrial Bioenergetics in Cultured Skeletal Muscle Cells.

The current study investigated the physiological effects of flavonoids found in daily consumed rooibos tea, aspalathin, isoorientin, and orientin on improving processes involved in mitochondrial function in C2C12 myotubes. To achieve this, C2C12 myotubes were exposed to a mitochondrial channel blocker, antimycin A (6.25 µM), for 12 h to induce mitochondrial dysfunction. Thereafter, cells were treated with aspalathin, isoorientin, and orientin (10 µM) for 4 h, while metformin (1 µM) and insulin (1 µM) were used as comparators. Relevant bioassays and real-time PCR were conducted to assess the impact of treatment compounds on some markers of mitochondrial function. Our results showed that antimycin A induced alterations in the mitochondrial respiration process and mRNA levels of genes involved in energy production. In fact, aspalathin, isoorientin, and orientin reversed such effects leading to the reduced production of intracellular reactive oxygen species. These flavonoids further enhanced the expression of genes involved in mitochondrial function, such as Ucp 2, Complex 1/3, Sirt 1, Nrf 1, and Tfam. Overall, the current study showed that dietary flavonoids, aspalathin, isoorientin, and orientin, have the potential to be as effective as established pharmacological drugs such as metformin and insulin in protecting against mitochondrial dysfunction in a preclinical setting; however, such information should be confirmed in well-established in vivo disease models.

Orientin Improves Substrate Utilization and the Expression of Major Genes Involved in Insulin Signaling and Energy Regulation in Cultured Insulin-Resistant Liver Cells.

Our group has progressively reported on the impact of bioactive compounds found in rooibos (Aspalathus linearis) and their capacity to modulate glucose homeostasis to improve metabolic function in experimental models of type 2 diabetes. In the current study, we investigated how the dietary flavone, orientin, modulates the essential genes involved in energy regulation to enhance substrate metabolism. We used a well-established hepatic insulin resistance model of exposing C3A liver cells to a high concentration of palmitate (0.75 mM) for 16 hrs. These insulin-resistant liver cells were treated with orientin (10 µM) for 3 h to assess the therapeutic effect of orientin. In addition to assessing the rate of metabolic activity, end point measurements assessed include the uptake or utilization of glucose and palmitate, as well as the expression of genes involved in insulin signaling and regulating cellular energy homeostasis. Our results showed that orientin effectively improved metabolic activity, mainly by maintaining substrate utilization which was marked by enhanced glucose and palmitate uptake by liver cells subjected to insulin resistance. Interestingly, these effects can be explained by the improvement in the expression of genes involved in glucose transport (Glut2), insulin signaling (Irs1 and Pi3k), and energy regulation (Ampk and Cpt1). These preliminary findings lay an important foundation for future research to determine the bioactive properties of orientin against dyslipidemia or insulin resistance in reliable and well-established models of type 2 diabetes.

The Potential Role of Polyphenols in Modulating Mitochondrial Bioenergetics within the Skeletal Muscle: A Systematic Review of Preclinical Models.

Polyphenols are naturally derived compounds that are increasingly being explored for their various health benefits. In fact, foods that are rich in polyphenols have become an attractive source of nutrition and a potential therapeutic strategy to alleviate the untoward effects of metabolic disorders. The last decade has seen a rapid increase in studies reporting on the bioactive properties of polyphenols against metabolic complications, especially in preclinical models. Various experimental models involving cell cultures exposed to lipid overload and rodents on high fat diet have been used to investigate the ameliorative effects of various polyphenols against metabolic anomalies. Here, we systematically searched and included literature reporting on the impact of polyphenols against metabolic function, particularly through the modulation of mitochondrial bioenergetics within the skeletal muscle. This is of interest since the skeletal muscle is rich in mitochondria and remains one of the main sites of energy homeostasis. Notably, increased substrate availability is consistent with impaired mitochondrial function and enhanced oxidative stress in preclinical models of metabolic disease. This explains the general interest in exploring the antioxidant properties of polyphenols and their ability to improve mitochondrial function. The current review aimed at understanding how these compounds modulate mitochondrial bioenergetics to improve metabolic function in preclinical models on metabolic disease.

Natural killer cell levels in adults living with type 2 diabetes: a systematic review and meta-analysis of clinical studies.

BACKGROUND: Chronic immune activation and hyperglycaemia are a hallmark of type 2 diabetes mellitus (T2D) while natural killer (NK) cells are involved in the pathogenesis of T2D. Dysregulated NK cell responses are associated with an increased risk of cardiovascular disease in patients living with T2D. OBJECTIVE: To provide a comprehensive and systematic evidence-based estimate on the levels of NK cells in patients living with T2D. RESULTS: This systematic review and meta-analysis included 13 studies reporting on 491 adult patients with T2D and 1064 nondiabetic controls. The pooled effect estimates showed increased levels of NK cells in adult patients with T2D compared to controls (MD: 0.03 [- 3.20, 3.26], I2 = 97%, p < 0.00001). CONCLUSION: Overall, the evidence presented in this systematic review shows that the changes in NK cells in patients living with T2D are still unclear and further studies are needed.

A systematic review on the functional role of Th1/Th2 cytokines in type 2 diabetes and related metabolic complications.

The T-helper (Th1/Th2) paradigm is widely studied for its role in modulating an adaptive immune response, especially in relation to the onset of various autoimmune diseases. In fact, emerging evidence clearly shows an inverse relationship between Th1/Th2 cytokines and the development of type 2 diabetes (T2D) complications, which is accelerated by an exacerbated inflammatory state. Here, relevant studies reporting on any association between the levels of Th1/Th2 cytokines and the development of T2D were retrieved through major electronic databases such as The Cochrane Library, Embase and PubMed. Extracted evidence which mostly involved animal models and human subjects with T2D or metabolic syndrome was assessed for quality and risk of bias using the Downs and Black checklist and Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines. Results strongly correlated raised Th1/Th2 cytokines such as interferon-gamma (IFN-γ)/interleukin (IL)-5 and IL-2/IL-5 ratios to T2D, and this was positively linked with the other complications including retinopathy and cardiovascular complications. Further, logistic regression analysis demonstrated that the Th1/Th2 ratios were significantly associated with impaired glucose homeostasis, abnormally enhanced lipid profiles, and insulin resistance. Although more studies making use of a larger sample size are required, current data suggest that optimal modulation of Th1/Th2 cytokines may be an important aspect in the management of T2D and its associated complications.

Isoorientin: A dietary flavone with the potential to ameliorate diverse metabolic complications.

Isoorientin is a natural C-glucosyl flavone that is generating a lot of interest due to its multiple pharmacological activities. Increasing experimental data have shown that the robust antioxidant and anti-inflammatory properties of isoorientin remain important in ameliorating a number of metabolic complications. In fact, plants rich in isoorientin have demonstrated strong ameliorative properties against complications such as hyperglycemia, hyperlipidemia, and insulin resistance. However, while such evidence is accumulating, it has not been reviewed to better inform on the therapeutic potential of this flavone in improving human health. This review examines and extrapolates available literature on the potential beneficial or detrimental effects associated with the use of isoorientin in mitigating metabolic diseases, with a specific focus on diabetes, obesity, and insulin resistance, including associated complications. The discussion includes effective doses in various experimental settings and proposed molecular mechanisms by which isoorientin may exert its therapeutic effects. In addition, the protective effects of extracts of a number of isoorientin-rich plants against metabolic complications will be highlighted.

Coenzyme Q10 Supplementation Improves Adipokine Levels and Alleviates Inflammation and Lipid Peroxidation in Conditions of Metabolic Syndrome: A Meta-Analysis of Randomized Controlled Trials.

Evidence from randomized controlled trials (RCTs) suggests that coenzyme Q10 (CoQ10) can regulate adipokine levels to impact inflammation and oxidative stress in conditions of metabolic syndrome. Here, prominent electronic databases such as MEDLINE, Cochrane Library, and EMBASE were searched for eligible RCTs reporting on any correlation between adipokine levels and modulation of inflammation and oxidative stress in individuals with metabolic syndrome taking CoQ10. The risk of bias was assessed using the modified Black and Downs checklist, while the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool was used to evaluate the quality of evidence. Results from the current meta-analysis, involving 318 participants, showed that CoQ10 supplementation in individuals with metabolic syndrome increased adiponectin levels when compared to those on placebo (SMD: 1.44 [95% CI: -0.13, 3.00]; I2 = 96%, p < 0.00001). Moreover, CoQ10 supplementation significantly lowered inflammation markers in individuals with metabolic syndrome in comparison to those on placebo (SMD: -0.31 [95% CI: -0.54, -0.08]; I2 = 51%, p = 0.07). Such benefits with CoQ10 supplementation were related to its ameliorative effects on lipid peroxidation by reducing malondialdehyde levels, concomitant to improving glucose control and liver function. The overall findings suggest that optimal regulation of adipokine function is crucial for the beneficial effects of CoQ10 in improving metabolic health.