Adiponectin plays a key role in the regulation of the whole-body energy homeostasis by modulating glucose and lipid metabolism. Although obesity-induced reduction of adiponectin expression is primarily ascribed to a transcriptional regulation failure, the underlying mechanisms are largely undefined. Here we show that DNA hypermethylation of a particular region of the adiponectin promoter suppresses adiponectin expression through epigenetic control and, in turn, exacerbates metabolic diseases in obesity. Obesity-induced, pro-inflammatory cytokines promote DNMT1 expression and its enzymatic activity. Activated DNMT1 selectively methylates and stimulates compact chromatin structure in the adiponectin promoter, impeding adiponectin expression. Suppressing DNMT1 activity with a DNMT inhibitor resulted in the amelioration of obesity-induced glucose intolerance and insulin resistance in an adiponectin-dependent manner. These findings suggest a critical role of adiponectin gene epigenetic control by DNMT1 in governing energy homeostasis, implying that modulating DNMT1 activity represents a new strategy for the treatment of obesity-related diseases.

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BackgroundSurgical and conservative methods have been reported by various studies for high rates of fracture union and subsequent regain of function among patients with undisplaced or minimally-displaced scaphoid fractures. Hence, this study aims to analyze the best available evidence to comprehend the relative benefits and risks of these therapeutic options.MethodsA systematic search of the literature from different databases and search engines was performed with strict eligibility criteria to obtain the highest quality of evidence. All randomized controlled trials delineating the outcomes of surgical versus conservative treatments for acute undisplaced or minimally-displaced scaphoid fractures were included and then evaluated using scoring tools: Cochrane risk of bias tool and PEDro scale. Data were pooled using random-effects models with standard mean differences for continuous outcomes and risk ratios for dichotomous variables.ResultsThe search yielded 339 potentially related articles, further trimmed down to eight studies based on the eligibility criteria. The meta-analysis revealed that surgical treatment resulted in significantly better functional outcomes than conservative treatment. Furthermore, surgery resulted in the prevention of delayed union of fractures and reduction of time needed to return to work.ConclusionsWhile four studies reported advantages of surgical treatment, evidence was insufficient to provide a definitive conclusion that surgery is a better option. Due to the significant limitations with respect to certain variables, the superiority of one method to the other could not be established.