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Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic fat accumulation in the absence of excessive alcohol consumption and is strongly associated with obesity, type 2 diabetes (T2DM) and other metabolic syndrome features. NAFLD is becoming increasingly prevalent and currently constitutes the leading cause of hepatocellular carcinoma (HCC). Recently, the term metabolic (dysfunction) associated fatty liver disease (MAFLD) has been proposed reflecting more accurately the underlying pathogenesis and the cardiometabolic disorders associated to NAFLD/MAFLD. Given the vital metabolic functions of the liver to maintain the body homeostasis, an extended endoplasmic reticulum (ER) network is mandatory in hepatocytes to retain its capacity to adapt to the multiple extracellular and intracellular signals mediating metabolic changes. Dysfunction of hepatocyte ER homeostasis and disturbance of its interaction with mitochondria have been recognized to be involved in the NAFLD pathophysiology. Apart from hepatocytes, hepatic stellate cells, and Kupffer cells have been shown to play an important role in the occurrence of NAFLD and progression to nonalcoholic steatohepatitis (NASH) with possibly different roles in the different stages of the NAFLD spectrum. Furthermore, excess lipid accumulation in the liver causes lipotoxicity which interacts with ER stress and culminates in inflammation and hepatocellular damage, mechanisms crucially implicated in NASH pathogenesis. Finally, the circadian clock machinery regulates ER stress-related pathways and vice versa, thus controlling the homeostasis of the liver metabolism and being implicated in the NAFLD progression. This review presents a comprehensive overview of the current knowledge supporting the impact of ER stress signaling on NAFLD, whilst summarizing potential therapeutic interventions targeting this process.

Aims: Polycystic ovary syndrome (PCOS) is a common condition that affects approximately 20% of reproductive‐aged women. PCOS is also associated with insulin resistance; women with PCOS are more insulin resistant than body mass index–matched controls. Methods: A systematic review was completed; randomised controlled trials that compared physical activity with control groups were evaluated in a meta‐analysis. Outcomes related to glucose homeostasis were analysed. Change from baseline to end of intervention values were reported as mean difference (MD) and 95% confidence intervals (CI). Results: There was evidence of a favourable effect of exercise on fasting insulin levels (MD −2.62 μIU/ml, CI −4.46 to −0.77; I2 = 92%; 236 participants, eight trials), but not for fasting blood glucose. Reductions in fasting insulin were found for all exercise modalities (aerobic, resistance or combined exercise), but were strongest in resistance training groups (MD −3.99 μIU/ml, CI −5.97 to −2.00; I2 = 54%; 50 participants, three trials). Change from baseline HOMA index also favoured exercise (MD −0.59, CI −1.02 to −0.17; I2 = 89%; 146 participants, seven trials) but evidence of effect was only present in aerobic exercise groups (MD −0.77, CI −1.28 to −0.26; I2 = 65%; 75 participants, four trials). Summary: Exercise, regardless of modality, reduces fasting insulin, but not fasting blood glucose, in women with PCOS compared with those receiving no intervention. However, a cautious approach should be adopted in interpreting these findings due to the wide CIs and evidence of considerable heterogeneity. Despite the statistically significant results, it is unclear if these improvements are clinically relevant.

Background Visceral adiposity index (VAI) is a novel marker of visceral adipose tissue accumulation and dysfunction. The study aim was to explore the association of VAI with the 10-year type 2 diabetes mellitus (T2DM) incidence in apparently healthy individuals and compare its T2DM predictive ability against common anthropometric indices. Methods In 2001 to 2002, the ATTICA study (Greece) recruited a random sample of 1514 and 1528 CVD-free men (18-87 years old) and women (18-89 years old), respectively. Sociodemographic, lifestyle, clinical, and biochemical characteristics of participants were measured at baseline, and the 10-year follow-up was performed during 2011 to 2012. After excluding participants with diabetes at baseline and participants without complete follow-up information regarding diabetes status and/or baseline VAI values, the working sample consisted of 1049 participants. In this sample, the predictive value of baseline VAI value was studied in relation to 10-year diabetes incidence. Results One hundred thirty-three incident cases of diabetes were documented (10-year incidence: 12.7%). In the fully adjusted model, VAI significantly increased diabetes risk by 22% (OR per 1-unit increase =1.22; 95%CI, 1.09-1.37). Markers of oxidative stress and inflammation were found to, at least partly, mediate this relationship. Also, a moderating effect of menstruation status was revealed among women. VAI showed the highest predictive ability and contributed the most, along with waist-to-height ratio, to the correct classification of participants who developed diabetes. Conclusions The present findings suggest that VAI may be a useful index for predicting long-term diabetes development and may exhibit better predictive ability to commonly used anthropometric indices.

Polycystic ovarian syndrome (PCOS) is a heterogenous disorder associated with clinical, endocrine and ultrasonographic features that can also be encountered in a number of other diseases. It has traditionally been suggested that prolactin excess, enzymatic steroidogenic abnormalities and thyroid disorders need to be excluded before a diagnosis of PCOS is made. However, there is paucity of data regarding the prevalence of PCOS phenotype in some of these disorders, whereas other endocrine diseases that exhibit PCOS-like features may elude diagnosis and proper management if not considered. This article reviews the data of currently included entities that exhibit a PCOS phenotype and those that potentially need to be looked for, and attempts to identify specific features that distinguish them from idiopathic PCOS.

Minority ethnic/non-White populations are more prone to weight gain and more susceptible to obesity-related complications. The objective of this study was to systematically review dietary and lifestyle interventions for weight management in minority ethnic groups. Electronic databases and reference lists of original studies and reviews were searched for studies on dietary and lifestyle weight management interventions published. Randomized clinical trials with ≥6-month duration were included. Nineteen studies met the inclusion criteria. Fourteen studies involved African-Americans, one in non-White Hispanics, one in Japanese Americans and three in both African-Americans and non-White Hispanics. Most of the interventions proved relatively effective. However, significant drawbacks were noted for several of these studies, such as small sample size, high attrition rates and lack of follow-up data. Better quality and long-term trials are required in order to investigate in detail the effectiveness of lifestyle changes for weight management in these populations and eventually support evidence-based recommendations.