Dietary restriction (DR) reduces adiposity and improves metabolism in patients with one or more symptoms of metabolic syndrome. Nonetheless, it remains elusive whether the benefits of DR in humans are mediated by calorie or nutrient restriction. This study was conducted to determine whether isocaloric dietary protein restriction is sufficient to confer the beneficial effects of dietary restriction in patients with metabolic syndrome. We performed a prospective, randomized controlled dietary intervention under constant nutritional and medical supervision. Twenty-one individuals diagnosed with metabolic syndrome were randomly assigned for caloric restriction (CR; n = 11, diet of 5941 ± 686 KJ per day) or isocaloric dietary protein restriction (PR; n = 10, diet of 8409 ± 2360 KJ per day) and followed for 27 days. Like CR, PR promoted weight loss due to a reduction in adiposity, which was associated with reductions in blood glucose, lipid levels, and blood pressure. More strikingly, both CR and PR improved insulin sensitivity by 62.3% and 93.2%, respectively, after treatment. Fecal microbiome diversity was not affected by the interventions. Adipose tissue bulk RNA-Seq data revealed minor changes elicited by the interventions. After PR, terms related to leukocyte proliferation were enriched among the upregulated genes. Protein restriction is sufficient to confer almost the same clinical outcomes as calorie restriction without the need for a reduction in calorie intake. The isocaloric characteristic of the PR intervention makes this approach a more attractive and less drastic dietary strategy in clinical settings and has more significant potential to be used as adjuvant therapy for people with metabolic syndrome.

Alterations in microRNA (miRNA) processing have been previously linked to aging. Here we used the small molecule enoxacin to pharmacologically interfere with miRNA biogenesis and study how it affects aging in C. elegans. Enoxacin extended worm lifespan and promoted survival under normal and oxidative stress conditions. Enoxacin-induced longevity required the transcription factor SKN-1/Nrf2 and was blunted by the antioxidant N-acetyl-cysteine, suggesting a prooxidant-mediated mitohormetic response. The longevity effects of enoxacin were also dependent on the miRNA pathway, consistent with changes in miRNA expression elicited by the drug. Among these differentially expressed miRNAs, the widely conserved miR-34-5p was found to play an important role in enoxacin-mediated longevity. Enoxacin treatment down-regulated miR-34-5p and did not further extend lifespan of long-lived mir-34 mutants. Moreover, N-acetyl-cysteine abrogated mir-34(gk437)-induced longevity. Evidence also points to double-stranded RNA-specific adenosine deaminases (ADARs) as new targets of enoxacin since ADAR loss-of-function abrogates enoxacin-induced lifespan extension. Thus, enoxacin increases lifespan by reducing miR-34-5p levels, interfering with the redox balance and promoting healthspan.

Background: Bariatric surgery, especially Roux-en-Y gastric bypass (RYGB), is the most effective and durable treatment option for severe obesity. The mechanisms involving adipose tissue may be important to explain the effects of surgery.Methods: We aimed to identify the genetic signatures of adipose tissue in patients undergoing RYGB. We evaluated 13 obese, non-diabetic patients (mean age 37 years, 100% women, Body mass index (BMI) 42.2 kg/m²) one day before surgery, 3 and 6 months (M) after RYGB.Results: Analysis of gene expression in adipose tissue collected at surgery compared with samples collected at 3 M and 6 M Post-RYGB showed that interleukins [Interleukin 6, Tumor necrosis factor-α(TNF-α), and Monocyte chemoattractant protein-1(MCP1)] and endoplasmic reticulum stress (ERS) genes [Eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3) and Calreticulin (CALR)] decreased during the follow-up (P ≤ 0.01 for all). Otherwise, genes involved in energy homeostasis [Adiponectin and AMP-activated protein kinase (AMPK)], cellular response to oxidative stress [Sirtuin 1, Sirtuin 3, and Nuclear factor erythroid 2-related factor 2 (NRF2)], mitochondrial biogenesis [Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α)] and amino acids metabolism [General control nonderepressible 2 (GCN2)] increased from baseline to all other time points evaluated (P ≤ 0.01 for all). Also, expression of Peroxisome proliferator-activated receptor gamma (PPARϒ) (adipogenesis regulation) was significantly decreased after RYGB (P < 0.05). Additionally, we observed that PGC1α, SIRT1 and AMPK strongly correlated to BMI at 3 M (P ≤ 0.01 for all), as well as ADIPOQ and SIRT1 to BMI at 6 M (P ≤ 0.01 for all).Conclusions: Our findings demonstrate that weight loss is associated with amelioration of inflammation and ERS and increased protection against oxidative stress in adipose tissue. These observations are strongly correlated with a decrease in BMI and essential genes that control cellular energy homeostasis, suggesting an adaptive process on a gene expression level during the caloric restriction and weight loss period after RYGB.Trial registrationCAAE: 73,585,317.0.0000.5440

Dietary omega-3 fatty acids have been efficacious in decreasing serum cholesterol levels and reducing the risk of cardiovascular disease. However, the metabolic and molecular changes induced by the omega-3 fatty acid α-linolenic acid (ALA), which ...

Aim: To determine whether continuous glucose monitoring (CGM) can reduce hypoglycaemia in patients with post‐bariatric hypoglycaemia (PBH). Materials and Methods: In an open‐label, nonrandomized, pre‐post design with sequential assignment, CGM data were collected in 22 individuals with PBH in two sequential phases: (i) masked (no access to sensor glucose or alarms); and (ii) unmasked (access to sensor glucose and alarms for low or rapidly declining sensor glucose). Twelve participants wore the Dexcom G4 device for a total of 28 days, while 10 wore the Dexcom G6 device for a total of 20 days. Results: Participants with PBH spent a lower percentage of time in hypoglycaemia over 24 hours with unmasked versus masked CGM (<3.3 mM/L, or <60 mg/dL: median [median absolute deviation {MAD}] 0.7 [0.8]% vs. 1.4 [1.7]%, P = 0.03; <3.9 mM/L, or 10 mM/L, or 180 mg/dL: median [MAD] 1.9 [2.2]% vs. 3.9 [3.6]%; P = 0.02). Conclusions: Real‐time CGM data and alarms are associated with reductions in low sensor glucose, elevated sensor glucose, and glycaemic variability. This suggests CGM allows patients to detect hyperglycaemic peaks and imminent hypoglycaemia, allowing dietary modification and self‐treatment to reduce hypoglycaemia. The use of CGM devices may improve safety in PBH, particularly for patients with hypoglycaemia unawareness.

Night work has become necessary in our modern society. However, sleep deprivation induces a circadian misalignment that effectively contributes to the development of diseases associated with metabolic syndrome, such as obesity and diabetes. Here, we evaluated the pattern of circadian clock genes and endoplasmic reticulum stress (ERS) genes in addition to metabolic and anthropometric measures in subjects that work during a nocturnal period compared with day workers. We study 20 night workers (NW) and 20 day workers (DW) submitted to a work schedule of 12 h of work for 36 h of rest for at least 5 years in a hospital. The present report shows that NW have increased fasting blood glucose, glycated hemoglobin (HbA1c), triglycerides, and low-density lipoprotein (LDL)-cholesterol levels, and lower high-density lipoprotein (HDL)-cholesterol levels compared to DW. In addition, we observed that waist circumference (WC), waist–hip ratio (WHR), and systemic blood pressure are also increased in NW. Interestingly, gene expression analysis showed changes in CLOCK gene expression in peripheral blood mononuclear cells (PBMC) samples of NW compared to the DW, evidencing a peripheral circadian misalignment. This metabolic adaptation was accompanied by the up-regulation of many genes of ERS in NW. These findings support the hypothesis that night shift work results in disturbed glycemic and lipid control and affects the circadian cycle through the deregulation of peripheral CLOCK genes, which is possibly due to the activation of ERS. Thus, night work induces important metabolic changes that increase the risk of developing metabolic syndrome.