The Role of Glucose and Fatty Acid Metabolism in the Development of Insulin Resistance in Skeletal Muscle

The rapid rise in the prevalence of obesity and diabetes has significantly contributed to the increasing global burden of noncommunicable diseases. Insulin resistance is a major underpinning etiology of both obesity and type 2 diabetes. Insulin resistance is characterized by a reduced response of skeletal, liver, and fat tissues to the actions of insulin hormone. Although detailed mechanisms implicated in the development of insulin resistance remain plausible, skeletal muscles have been identified to play an integral role in the improvement of insulin sensitivity in the diseased state. The effective modulation of glucose and fatty acid metabolism in the skeletal muscle through exercise or by certain therapeutics has been associated with reversal of insulin resistance and amelioration of diabetes associated complications such as inflammation and oxidative stress. This chapter will briefly discuss the role of glucose and fatty acid metabolism in the development of insulin resistance in the skeletal muscle

N-Acetyl Cysteine Targets Hepatic Lipid Accumulation to Curb Oxidative Stress and Inflammation in NAFLD: A Comprehensive Analysis of the Literature

Abstract: Impaired adipose tissue function and insulin resistance remain instrumental in promoting hepatic lipid accumulation in conditions of metabolic syndrome. In fact, enhanced lipid accumulation together with oxidative stress and an abnormal inflammatory response underpin the development and severity of non-alcoholic fatty liver disease (NAFLD). There are currently no specific protective drugs against NAFLD, and effective interventions involving regular exercise and healthy diets have proved difficult to achieve and maintain. Alternatively, due to its antioxidant and anti-inflammatory properties, there has been growing interest in understanding the therapeutic effects of N-acetyl cysteine (NAC) against metabolic complications, including NAFLD. Here, reviewed evidence suggests that NAC blocks hepatic lipid accumulation in preclinical models of NAFLD. This is in part through the effective regulation of a fatty acid scavenger molecule (CD36) and transcriptional factors such as sterol regulatory element-binding protein (SREBP)-1c/-2 and peroxisome proliferator-activated receptor gamma (PPARγ). Importantly, NAC appears effective in improving liver function by reducing pro-inflammatory markers such as interleukin (IL)-6 IL-1β, tumour necrosis factor alpha (TNF-α) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). This was primarily through the attenuation of lipid peroxidation and enhancements in intracellular response antioxidants, particularly glutathione. Very few clinical studies support the beneficial effects of NAC against NAFLD-related complications, thus well-organized randomized clinical trials are still necessary to confirm its therapeutic potential

Skeletal Muscle as a Therapeutic Target for Natural Products to Reverse Metabolic Syndrome

Natural compounds, especially polyphenols have become a popular area of research mainly due to their apparent health benefits. Increasing the phenolic content of a diet, apart from its antioxidant benefit, has a beneficial effect on signaling molecules involved in carbohydrate and lipid metabolism. These effects could potentially protect against metabolic syndrome, a cluster of metabolic complications such as obesity, insulin resistance and type 2 diabetes that is characterized by a dysregulated carbohydrate, and lipid metabolism. Research continues to investigate various natural compounds for their amelioration of impaired signaling mechanisms that may lead to dysregulated metabolism to find means to improve the life expectancy of patients with metabolic syndrome. In this chapter, a systematic search through major databases such as MEDLINE/PubMed, EMBASE, and Google Scholar of literature reporting on the ameliorative potential of commonly investigated natural products that target skeletal muscle to ameliorate metabolic syndrome associated complications was conducted. The selected natural products that are discussed include apigenin, aspalathin, berberine, curcumin, epigallocatechin gallate, hesperidin, luteolin, naringenin, quercetin, resveratrol, rutin, and sulforaphane

Investigating cardiovascular risk in premenopausal women on oral contraceptives: Systematic review with meta-analysis

BackgroundThe use of oral contraceptives (OCs) is associated with an increased risk of cardiovascular events such as arterial and venous thrombosis (VTE). Cardiovascular diseases (CVDs) are the leading cause of death worldwide, with low- and middle-income nations accounting for over three-quarter of CVD deaths. The aim of this systematic review is to provide a comprehensive synthesis of the available evidence on the link between OC use and CVD risk in premenopausal women and to further assess the role of geographic disparities in the reported prevalence of CVD risk in women on OCs.MethodsA comprehensive search of databases such as MEDLINE, Academic Search Complete, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Health Source: Nursing/Academic Edition was conducted, right from the inception to the present, by using the EBSCOhost search engine. The Cochrane Central Register of Clinical trials (CENTRAL) was also searched to augment relevant sources of information. OpenGrey, which is a repository of information providing open access to bibliographical references, was searched and the reference list of the selected studies was also scanned. The potential risk of bias of the included studies was assessed using the modified Downs and Black checklist. Data analysis was performed using the Review Manager (RevMan) version 5.3.ResultsWe included 25 studies that comprised 3,245 participants, of which 1,605 (49.5%) are OC users, while 1,640 (50.5%) are non-OC users. A total of 15 studies were included for meta-analysis, and the overall pooled estimates suggested a significant increase in the traditional cardiovascular risk variables [standardized mean difference (SMD) = 0.73, (0.46, 0.99) (Z = 5.41, p < 0.001)] and little to no difference in endothelial activation among OC users when compared with non-OC users [SMD = −0.11, (−0.81, 0.60) (Z = 0.30, p = 0.76)]. Europe [SMD = 0.03, (−0.21, 0.27), (Z = 0.25 p = 0.88)] had the least effect size, while North America had the highest effect size [SMD = 1.86, (−0.31, 4.04), (Z = 1.68 p = 0.09)] for CVD risk in OC users when compared with non-OC users.ConclusionThe use of OCs suggests a significant increase in the prevalence of traditional cardiovascular risk variables with little to no difference in the risk of endothelial dysfunction when compared with non-OC users, and the magnitude of CVD risks varies across different geographical regions.Registration and protocolThis systematic review was registered in the international prospective register of systematic reviews (PROSPERO) under the registration number: CRD42020216169

Vitamin C intake potentially lowers total cholesterol to improve endothelial function in diabetic patients at increased risk of cardiovascular disease: A systematic review of randomized controlled trials

Background: Vitamin C is one of the most consumed dietary compounds and contains abundant antioxidant properties that could be essential in improving metabolic function. Thus, the current systematic review analyzed evidence on the beneficial effects of vitamin C intake on cardiovascular disease (CVD)-related outcomes in patients with diabetes or metabolic syndrome. Methods: To identify relevant randomized control trials (RCTs), a systematic search was run using prominent search engines like PubMed and Google Scholar, from beginning up to March 2022. The modified Black and Downs checklist was used to assess the quality of evidence. Results: Findings summarized in the current review favor the beneficial effects of vitamin C intake on improving basic metabolic parameters and lowering total cholesterol levels to reduce CVD-risk in subjects with type 2 diabetes or related metabolic diseases. Moreover, vitamin C intake could also reduce the predominant markers of inflammation and oxidative stress like C-reactive protein, interleukin-6, and malondialdehyde. Importantly, these positive outcomes were consistent with improved endothelial function or increased blood flow in these subjects. Predominantly effective doses were 1,000 mg/daily for 4 weeks up to 12 months. The included RCTs presented with the high quality of evidence. Conclusion: Clinical evidence on the beneficial effects of vitamin C intake or its impact on improving prominent markers of inflammation and oxidative stress in patients with diabetes is still limited. Thus, more RCTs are required to solidify these findings, which is essential to better manage diabetic patients at increased risk of developing CVD

A Review on the Antidiabetic Properties of Moringa oleifera Extracts: Focusing on Oxidative Stress and Inflammation as Main Therapeutic Targets

Moringa oleifera is one of the popular plants that have shown significant health benefits. Certainly, preclinical evidence (predominantly from animal models) summarized in the current review supports the beneficial effects of Moringa oleifera leaf extracts in combating the prominent characteristic features of diabetes mellitus. This includes effective control of blood glucose or insulin levels, enhancement of insulin tissue sensitivity, improvement of blood lipid profiles, and protecting against organ damage under sustained conditions of hyperglycemia. Interestingly, as major complications implicated in the progression of diabetes, including organ damage, Moringa oleifera leaf and seed extracts could efficiently block the detrimental effects of oxidative stress and inflammation in these preclinical models. Notably, these extracts (especially leaf extracts) showed enhanced effects in strengthening intracellular antioxidant defences like catalase, superoxide dismutase, and glutathione to lower lipid peroxidation products and reduce prominent pro-inflammatory markers such as tumor necrosis factor-α, interleukin (1L)-β, IL-6, monocyte chemoattractant protein-1 and nitric oxide synthase. From animal models of diabetes, the common and effective dose of leaf extracts of Moringa oleifera was 100–300 mg/kg, within the treatment duration of 2–8 weeks. Whereas supplementation with approximately 20 g leaf powder of Moringa oleifera for at least 2 weeks could improve postprandial blood glucose in subjects with prediabetes or diabetes. Although limited clinical studies have been conducted on the antidiabetic properties of Moringa oleifera, current findings provide an important platform for future research directed at developing this plant as a functional food to manage diabetic complications

Physical exercise potentially targets epicardial adipose tissue to reduce cardiovascular disease risk in patients with metabolic diseases : oxidative stress and inflammation emerge as major therapeutic targets

CITATION: Nyawo, T. A. et al. 2021. Physical exercise potentially targets epicardial adipose tissue to reduce cardiovascular disease risk in patients with metabolic diseases : oxidative stress and inflammation emerge as major therapeutic targets. Antioxidants, 10(11):1758, doi:10.3390/antiox10111758.The original publication is available at https://www.mdpi.comENGLISH ABSTRACT: Excess epicardial adiposity, within a state of obesity and metabolic syndrome, is emerging as an important risk factor for the development of cardiovascular diseases (CVDs). Accordingly, increased epicardial fat thickness (EFT) implicates the exacerbation of pathological mechanisms involving oxidative stress and inflammation within the heart, which may accelerate the development of CVDs. This explains increased interest in targeting EFT reduction to attenuate the detrimental effects of oxidative stress and inflammation within the setting of metabolic syndrome. Here, we critically discuss clinical and preclinical evidence on the impact of physical exercise on EFT in correlation with reduced CVD risk within a setting of metabolic disease. This review also brings a unique perspective on the implications of oxidative stress and inflammation as major pathological consequences that link increased EFT to accelerated CVD risk in conditions of metabolic disease.https://www.mdpi.com/2076-3921/10/11/1758Publisher's versio

Coenzyme Q10 supplementation improves adipokine levels and alleviates inflammation and lipid peroxidation in conditions of metabolic syndrome : a meta-analysis of randomized controlled trials

CITATION: Dludla, P. V., et al. 2020. Q10 Supplementation Improves Adipokine Levels and Alleviates Inflammation and Lipid Peroxidation in Conditions of Metabolic Syndrome: A Meta-Analysis of Randomized Controlled Trials. International Journal of Molecular Sciences. 2020; 21(9). doi:10.3390/ijms21093247The original publication is available at https://www.mdpi.com/journal/ijmsEvidence 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.https://www.mdpi.com/1422-0067/21/9/3247/htmPublishers versio

Global and gene-specific DNA methylation in adult type 2 diabetic individuals: a protocol for a systematic review

Abstract Background DNA methylation (global and gene-specific) has been reported as an epigenetic mechanism that could be involved in the pathogenesis of type 2 diabetes mellitus (T2DM). Furthermore, epigenetic therapy has been suggested as a future possibility for T2DM treatment. Epigenetic changes illustrate the environmental link of the disease. Since some of the epigenetic modifications can be reversed, they could be used as potential therapeutic targets. The aim of the systematic review will be to synthesise the available evidence pertaining to the link between DNA methylation and T2DM. The systematic review will evaluate characteristics of reported studies such as the source of DNA used, methods of quantifying DNA methylation and the participants’ demographics (age, gender, race and adiposity). We will conduct a narrative synthesis of data, and if there are an adequate number of sufficiently homogenous studies, we will consider performing a meta-analysis. The review will evaluate if the levels of DNA methylation are a possible risk factor for T2DM. Furthermore, we will assess whether DNA methylation is a plausible biomarker and therapeutic target for the treatment and management of T2DM. Methods This systematic review protocol will be reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) 2015 statement. An extensive search for original research articles, published since inception, was performed on major databases such as Embase, MEDLINE and Cochrane Library. The search strategy will include a combination of key words and MeSH words. Literature that is available in English and studies in other languages that can be translated into English will be used. Data extraction will be done in duplicate, and two authors will independently screen for eligible studies using pre-defined criteria. The Cochrane Risk of Bias Assessment Tool and Joanna Briggs Institute (JBI) Critical Appraisal tools will be used to assess the risk of bias. The Grading of Recommendations, Assessment, Development and Evaluation assessment tool will be used to assess the overall quality of extracted data. Discussion This systematic review will evaluate published literature, assessing the link between DNA methylation and T2DM. Our findings could help guide future research evaluating epigenetic changes in T2DM and direct future therapeutic interventions

Effect of combined oral contraceptive on cardiorespiratory function and immune activation in premenopausal women involved in exercise: A systematic review protocol.

BackgroundThe use of combined oral contraceptive (COC) is common among women of reproductive age despite the potential risk of them developing thrombotic events. There is a need to understand how COC affects cardiorespiratory function and markers of immune activation in premenopausal women involved in exercise. This highlights a need for a systematic review to enhance our understanding of how the use of COC affects cardiovascular health in premenopausal women subjected to exercise.MethodThis systematic review protocol was prepared following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) 2015 statement. An extensive search of relevant literature by two independent reviewers will be conducted through the EBSCOhost interface to access databases such as MEDLINE, EMBASE, and CINAHL. Other health sources, including Cochrane CENTRAL, unpublished studies and grey literature, will also be searched. The search will include all studies that report the effect of COC on essential parameters of cardiorespiratory function and markers of immune activation in premenopausal women involved in exercise. All included studies will be appraised using appraisal tools, while appropriate extraction tools will be used for data extraction. Where possible, eligible studies will be pooled for meta-analysis. If statistical pooling is not feasible, our findings will be presented in a narrative format. The certainty of evidence will be assessed using the Grading of Recommendations, Assessment, Development and Evaluation Assessment (GRADE) tool.Trial registrationPROSPERO registration number: CRD42021265257