Role of Circadian Clock on the Pathogenesis and Lifestyle Management in Non-Alcoholic Fatty Liver Disease

Several features of the modern lifestyle, such as weekly schedules or irregular daily eating patterns, have become major drivers of global health problems, including non-alcoholic fatty liver disease (NAFLD). Sleep is an essential component of human well-being, and it has been observed that when circadian rhythms are disrupted, or when sleep quality decreases, an individual’s overall health may worsen. In addition, the discrepancy between the circadian and social clock, due to weekly work/study schedules, is called social jetlag and has also been associated with adverse metabolic profiles. Current management of NAFLD is based on dietary intake and physical activity, with circadian preferences and other environmental factors also needing to be taken into account. In this regard, dietary approaches based on chrononutrition, such as intermittent fasting or time-restricted feeding, have proven to be useful in realigning lifestyle behaviors with circadian biological rhythms. However, more studies are needed to apply these dietary strategies in the treatment of these patients. In this review, we focus on the impact of circadian rhythms and the role of sleep patterns on the pathogenesis and development of NAFLD, as well as the consideration of chrononutrition for the precision nutrition management of patients with NAFLD

Impact of acute consumption of beverages containing plant-based or alternative sweetener blends on postprandial appetite, food intake, metabolism, and gastro-intestinal symptoms: Results of the SWEET beverages trial

Project SWEET examined the barriers and facilitators to the use of non-nutritive sweeteners and sweetness enhancers (hereafter "S&SE") alongside potential risks/benefits for health and sustainability. The Beverages trial was a double-blind multi-centre, randomised crossover trial within SWEET evaluating the acute impact of three S&SE blends (plant-based and alternatives) vs. a sucrose control on glycaemic response, food intake, appetite sensations and safety after a carbohydrate-rich breakfast meal. The blends were: mogroside V and stevia RebM; stevia RebA and thaumatin; and sucralose and acesulfame-potassium (ace-K). At each 4 h visit, 60 healthy volunteers (53% male; all with overweight/obesity) consumed a 330 mL beverage with either an S&SE blend (0 kJ) or 8% sucrose (26 g, 442 kJ), shortly followed by a standardised breakfast (∼2600 or 1800 kJ with 77 or 51 g carbohydrates, depending on sex). All blends reduced the 2-h incremental area-under-the-curve (iAUC) for blood insulin (p 0.05 for all). Compared with sucrose, there was a 3% increase in LDL-cholesterol after stevia RebA-thaumatin (p < 0.001 in adjusted models); and a 2% decrease in HDL-cholesterol after sucralose-ace-K (p < 0.01). There was an impact of blend on fullness and desire to eat ratings (both p < 0.05) and sucralose-acesulfame K induced higher prospective intake vs sucrose (p < 0.001 in adjusted models), but changes were of a small magnitude and did not translate into energy intake differences over the next 24 h. Gastro-intestinal symptoms for all beverages were mostly mild. In general, responses to a carbohydrate-rich meal following consumption of S&SE blends with stevia or sucralose were similar to sucrose

Impact of acute consumption of beverages containing plant-based or alternative sweetener blends on postprandial appetite, food intake, metabolism, and gastro-intestinal symptoms: Results of the SWEET beverages trial

Project SWEET examined the barriers and facilitators to the use of non-nutritive sweeteners and sweetness enhancers (hereafter "S&SE") alongside potential risks/benefits for health and sustainability. The Beverages trial was a double-blind multi-centre, randomised crossover trial within SWEET evaluating the acute impact of three S&SE blends (plant-based and alternatives) vs. a sucrose control on glycaemic response, food intake, appetite sensations and safety after a carbohydrate-rich breakfast meal. The blends were: mogroside V and stevia RebM; stevia RebA and thaumatin; and sucralose and acesulfame-potassium (ace-K). At each 4h visit, 60 healthy volunteers (53% male; all with overweight/obesity) consumed a 330 mL beverage with either an S&SE blend (0 kJ) or 8% sucrose (26 g, 442 kJ), shortly followed by a standardised breakfast (∼2600 or 1800 kJ with 77 or 51 g carbohydrates, depending on sex). All blends reduced the 2-h incremental area-under-the-curve (iAUC) for blood insulin (p  0.05 for all). Compared with sucrose, there was a 3% increase in LDL-cholesterol after stevia RebA-thaumatin (p < 0.001 in adjusted models); and a 2% decrease in HDL-cholesterol after sucralose-ace-K (p < 0.01). There was an impact of blend on fullness and desire to eat ratings (both p < 0.05) and sucralose-acesulfame K induced higher prospective intake vs sucrose (p < 0.001 in adjusted models), but changes were of a small magnitude and did not translate into energy intake differences over the next 24h. Gastro-intestinal symptoms for all beverages were mostly mild. In general, responses to a carbohydrate-rich meal following consumption of S&SE blends with stevia or sucralose were similar to sucrose

Impact of PNPLA3 rs738409 Polymorphism on the Development of Liver-Related Events in Patients With Nonalcoholic Fatty Liver Disease

[Background and Aims] Nonalcoholic fatty liver disease (NAFLD) is a complex disease, resulting from the interplay between environmental determinants and genetic variations. Single nucleotide polymorphism rs738409 C>G in the PNPLA3 gene is associated with hepatic fibrosis and with higher risk of developing hepatocellular carcinoma. Here, we analyzed a longitudinal cohort of biopsy-proven NAFLD subjects with the aim to identify individuals in whom genetics may have a stronger impact on disease progression.[Methods] We retrospectively analyzed 756 consecutive, prospectively enrolled biopsy-proven NAFLD subjects from Italy, United Kingdom, and Spain who were followed for a median of 84 months (interquartile range, 65–109 months). We stratified the study cohort according to sex, body mass index (BMI) </≥30 kg/m2) and age (</≥50 years). Liver-related events (hepatic decompensation, hepatic encephalopathy, esophageal variceal bleeding, and hepatocellular carcinoma) were recorded during the follow-up and the log-rank test was used to compare groups.[Results] Overall, the median age was 48 years and most individuals were men (64.7%). The PNPLA3 rs738409 genotype was CC in 235 (31.1%), CG in 328 (43.4%), and GG in 193 (25.5%) patients. At univariate analysis, the PNPLA3 GG risk genotype was associated with female sex and inversely related to BMI (odds ratio, 1.6; 95% confidence interval, 1.1–2.2; P = .006; and odds ratio, 0.97; 95% confidence interval, 0.94–0.99; P = .043, respectively). Specifically, PNPLA3 GG risk homozygosis was more prevalent in female vs male individuals (31.5% vs 22.3%; P = .006) and in nonobese compared with obese NAFLD subjects (50.0% vs 44.2%; P = .011). Following stratification for age, sex, and BMI, we observed an increased incidence of liver-related events in the subgroup of nonobese women older than 50 years of age carrying the PNPLA3 GG risk genotype (log-rank test, P = .0047).[Conclusions] Nonobese female patients with NAFLD 50 years of age and older, and carrying the PNPLA3 GG risk genotype, are at higher risk of developing liver-related events compared with those with the wild-type allele (CC/CG). This finding may have implications in clinical practice for risk stratification and personalized medicine.Peer reviewe

Repositioning of the global epicentre of non-optimal cholesterol

High blood cholesterol is typically considered a feature of wealthy western countries(1,2). However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world(3) and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health(4,5). However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol-which is a marker of cardiovascular riskchanged from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million-4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.Peer reviewe

Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: A pooled analysis of 1018 population-based measurement studies with 88.6 million participants

© The Author(s) 2018. Background: Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure. Methods: We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20-29 years to 70-79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probittransformed) prevalence of raised blood pressure and age-group- and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure. Results: In 2005-16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the highincome Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association. Conclusions: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.Peer reviewe