Metabolic complications in an obese state can be aggravated by an abnormal inflammatory response and enhanced production of reactive oxygen species. Pro-inflammatory response is known to be associated with the formation of toxic reactive oxygen species and subsequent generation of oxidative stress. Indeed, adipocytes from obese individuals display an altered adipokine profile, with upregulated expression and secretion of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin (IL-6). Interestingly, natural compounds, including phenolic enriched foods are increasingly explored for their ameliorative effects against various metabolic diseases. Of interest is gallic acid, a trihydroxybenzoic acid that has progressively demonstrated robust anti-obesity capabilities in various experimental models. In addition to reducing excessive lipid storage in obese subjects, gallic acid has been shown to specifically target the adipose tissue to suppress lipogenesis, improve insulin signaling, and concomitantly combat raised pro-inflammatory response and oxidative stress. This review will revise mechanisms involved in the pathophysiological effects of inflammation and oxidative stress in an obese state. To better inform on its therapeutic potential and improvement of human health, available evidence reporting on the anti-obesity properties of gallic acid and its derivatives will be discussed, with emphases on its modulatory effect on molecular mechanisms involved in insulin signaling, inflammation and oxidative stress.

Background Antiretroviral therapy (ART) alters platelet reactivity, and as a consequence, patients living with HIV may be at an increased risk of cardiovascular disease (CVD). The current evidence on platelet activation levels in patients with HIV remains inconclusive. We therefore aimed to systematically synthesise evidence on the association of platelet activation in HIV-infected patients on successful treatment. Methods Electronic databases were searched from inception until November 2019. Studies were included if the primary or secondary outcome of the study was to assess platelet activation in HIV-infected patients on ART. The primary outcome of this review included the levels of platelet activation. The pooled effect estimates were calculated using a random-effects meta-analysis model. Results We identified 30 studies comprising of 2325 participants. The pooled estimates showed elevated levels of platelet activation in treatment-naïve HIV-infected patients compared to uninfected controls (Hedges’ g 2.00 [95%CI 1.05, 2.94]; z = 4.12, p < 0.0001). These remained elevated despite successful ART (Hedges’ g 2.05 [95%CI 0.58, 3.52]; z = 2.71, p = 0.0067). Conclusion The levels of platelet activation are elevated in treatment-naïve HIV-infected patients, and these persist during successful ART. Further studies should assess the clinical relevance of monitoring the levels of platelet activation in HIV-infected patients on ART.

The aim of this study is to quantify global DNA methylation and investigate the relationship with diabetes status and polymorphisms in MTHFR C677T and NOS3 G894T genes in mixed ancestry subjects from South Africa. Global DNA methylation was measured, and MTHFR rs1801133 and NOS3 rs1799983 polymorphisms were genotyped using high throughput real-time polymerase chain reaction and direct DNA sequencing. Of the 564 participants, 158 (28%) individuals had T2DM of which 97 (17.2%) were screen-detected cases. Another 119 (21.1%) had prediabetes, that is, impaired fasting glucose, impaired glucose tolerance, or the combination of both, and the remainder 287 (50.9%) had normal glucose tolerance. Global DNA methylation was significantly higher in prediabetes and screen-detected diabetes than in normal glucose tolerance (both p ≤ 0.033) and in screen-detected diabetes compared to known diabetes on treatment (p = 0.019). There was no difference in global DNA methylation between known diabetes on treatment and normal glucose tolerance (p > 0.999). In multivariable linear regression analysis, only NOS3 was associated with increasing global DNA methylation (β = 0.943; 95% CI: 0.286 to 1.560). The association of global DNA methylation with screen-detected diabetes but not treated diabetes suggests that glucose control agents to some extent may be reversing DNA methylation. The association between NOS3 rs1799983 polymorphisms and DNA methylation suggests gene-epigenetic mechanisms through which vascular diabetes complications develop despite adequate metabolic control.

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BackgroundDNA 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.MethodsThis 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.DiscussionThis 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.Electronic supplementary materialThe online version of this article (10.1186/s13643-018-0708-7) contains supplementary material, which is available to authorized users.