BackgroundThe endocannabinoid system (ECS) is a major regulator of synaptic plasticity and neuromodulation. Alterations of the ECS have been demonstrated in several animal models of autism spectrum disorder (ASD). In some of these models, activating the ECS rescued the social deficits. Evidence for dysregulations of the ECS in human ASD are emerging, but comprehensive assessments and correlations with disease characteristics have not been reported yet.MethodsSerum levels of the main endocannabinoids, N-arachidonoylethanolamine (AEA or anandamide) and 2-arachidonoylglycerol (2-AG), and their related endogenous compounds, arachidonic acid (AA), N-palmitoylethanolamine (PEA), and N-oleoylethanolamine (OEA), were analyzed by liquid chromatography/tandem mass spectrometry in 93 children with ASD (age = 13.1 ± 4.1, range 6–21; 79% boys) and 93 age- and gender-matched neurotypical children (age = 11.8 ± 4.3, range 5.5–21; 79% boys). Results were associated with gender and use of medications, and were correlated with age, BMI, and adaptive functioning of ASD participants as reflected by scores of Autism Diagnostic Observation Schedule (ADOS-2), Vineland Adaptive Behavior Scale-II (VABS-II), and Social Responsiveness Scale-II (SRS-2).ResultsChildren with ASD had lower levels (pmol/mL, mean ± SEM) of AEA (0.722 ± 0.045 vs. 1.252 ± 0.072, P < 0.0001, effect size 0.91), OEA (17.3 ± 0.80 vs. 27.8 ± 1.44, P < 0.0001, effect size 0.94), and PEA (4.93 ± 0.32 vs. 7.15 ± 0.37, P < 0.0001, effect size 0.65), but not AA and 2-AG. Serum levels of AEA, OEA, and PEA were not significantly associated or correlated with age, gender, BMI, medications, and adaptive functioning of ASD participants. In children with ASD, but not in the control group, younger age and lower BMI tended to correlate with lower AEA levels. However, these correlations were not statistically significant after a correction for multiple comparisons.ConclusionsWe found lower serum levels of AEA, PEA, and OEA in children with ASD. Further studies are needed to determine whether circulating endocannabinoid levels can be used as stratification biomarkers that identify clinically significant subgroups within the autism spectrum and if they reflect lower endocannabinoid “tone” in the brain, as found in animal models of ASD.Electronic supplementary materialThe online version of this article (10.1186/s13229-019-0256-6) contains supplementary material, which is available to authorized users.

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Vitamin D is thought to play a role in glucose metabolism. The aim of the present study was to determine the effect of vitamin D supplementation on markers of insulin sensitivity and inflammation in men without diabetes with vitamin D deficiency/insufficiency. In this 1-year double-blind randomized controlled trial, 130 men aged 20-65 years (mean age 47.52 ± 11.84 years) with serum 25-hydroxyvitamin D levels <50 nmol/l (mean 38.89 ± 8.64 nmol/l) were randomized to treatment (100 000 IU vitamin D bimonthly) or placebo. Anthropometric measurements, demographic questionnaires, and blood indices (fasting glucose, insulin, high-sensitivity C-reactive protein, lipids) were collected and repeated after 6 and 12 months. The compliance rate was 98.5%. Multivariate models, adjusted for baseline levels, age, body mass index, sun exposure, physical activity and LDL, showed significant differences in insulin and homeostatic model assessment of insulin resistance (HOMA-IR) values between groups. Levels of insulin and HOMA-IR values remained steady during the study period in the treatment group but increased by 16% in the control group (p = 0.038 and p = 0.048, respectively). Vitamin D supplementation administered for 12 months in healthy men maintained insulin levels and HOMA-IR values relative to the increase in the control group. Further studies are needed to establish the long-term effect of vitamin D supplementation on the risk of diabetes.

Background and Aims: Diabetes and dysglycemia increase the risk of frailty and decreased physical abilities. Adherence to the Mediterranean Diet (MD) may reduce this risk. We hypothesized that adherence to the MD is associated with physical function in older type-2 diabetic patients and that the association is stratified by age. Methods and Results: We recruited type-2 diabetes patients aged >60 years at the Center for Successful Aging with Diabetes at Sheba Medical Center. Health status and demographic data were obtained from medical records. Food Frequency Questionnaire was used for nutritional assessment and calculation of MD score. Physical function indices were determined by a physiotherapist and included: Berg Balance test, Timed Get-Up-and-Go, 6-min walk (6 MW), 10-m walk (10 MW), Four Square Step Test, 30-s chair stand and Grip strength, and activities and instrumental activities of daily living. Among 117 participants (age 70.6 ± 6.5), high adherence to MD was associated with better score on functional tests (low vs. high MD adherence: 9.7% vs. 25%, ANOVA p = 0.02). A significant age by MD interaction was found: a higher adherence to MD was associated with a better 6 MW (low vs. high: 387 ± 35 m vs. 483 ± 26 m; p = 0.001) and higher 10 MW (low vs. high: 1.8 ± 0.16 m/s vs. 2.0 ± 0.13 m/s; p = 0.02) in participants aged >75 years. These associations remained significant after controlling for gender, age, BMI, and physical activity. Conclusion: In the current study, we showed relationships between strength, physical performance, and MD among older diabetic patients. Future studies are needed to confirm this association and establish temporal relationships.

The prevalence of childhood and adolescence obesity is increasing to alarming proportions worldwide and poses a major public health problem by significantly elevating the risks of chronic diseases. There is strong evidence that childhood overweight and obesity are risk factors for severe obesity over the whole life course. In fact, longitudinal studies have found that most overweight/obese children would become overweight and obese adults. There is a lack of coupling in the scientific literature between adipose tissue development and biology to obesity prevention and treatment strategies. This is of utmost importance, especially regarding childhood and adolescence, as the major scientific paradigm in studies of adiposity is that the major number of adipocytes is set for life at this early age. This review discusses the current adipose cell biology paradigms to pinpoint the critical factors and periods in childhood overweight and obesity and, consecutively, to develop relevant prevention strategies.