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BackgroundBariatric 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.MethodsWe 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.ResultsAnalysis 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 ConclusionsOur 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

Roux-en-Y gastric bypass (RYGB) is the most effective and durable treatment option for reducing adiposity and control abnormalities of metabolic syndrome in patient with severe obesity. Some studies have shown that the initial effect of RYGB on improving metabolic parameters is due to caloric restriction. However, the impact of RYGB on adipose tissue is still under debate. We evaluated 13 obese, nondiabetic patients (mean age 37 years, 100% women, BMI 42.2 kg/m2) one day before surgery, 3 and 6 months (M) after RYGB. Changes in anthropometric, biochemical e gene expression were evaluated with ANOVA and Pearson’s correlation analysis. BMI, fat mass and blood pressure decreased after 3M and 6M (P≤0.05 for all) compared with baseline. Analysis of gene expression in adipose tissue collected at surgery compared with samples collected at 3M and 6M Post-RYGB showed that interleukins (IL6, TNF-α, and MCP1) and endoplasmic reticulum stress (ERS) genes (EIF2AK3 and CALR) decreased during the follow-up (P≤0.01 for all). Nonetheless, genes involved in energy homeostasis (ADIPOQ and AMPK), cellular response to oxidative stress (SIRT1, SIRT3, and NRF2), regulation of adipogenesis (PPARγ), mitochondrial biogenesis (PGC1α) and amino acid metabolism (GCN2) increased from baseline to all other time points evaluated (P≤0.01 for all). We also observed a strong positive correlation between PGC1α, SIRT1, and AMPK with BMI at 3M (P≤0.01 for all) and ADIPOQ and SIRT1 with BMI at 6M (P≤0.01 for all). 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, in a gene expression level, during the caloric restriction and weight loss period after RYGB in patients without diabetes. Disclosure R. Ferraz-Bannitz: None. C.R. Welendorf: None. P.O. Coelho: None. W. Salgado Jr.: None. C.B. Nonino: None. R.A. Beraldo: None. M. Foss-Freitas: None. Funding Ribeirao Preto Clinical Hospital-FAEPA

Muscle wasting or atrophy is extensively associated with human systemic diseases including diabetes, cancer, and kidney failure. Accumulating evidence from transcriptional profiles has noted that a common set of genes, termed atrogenes, is modulated in atrophying muscles. However, the transcriptional changes that trigger the reversion or attenuation of muscle atrophy have not been characterized at the molecular level until now. Here, we applied cDNA microarrays to investigate the transcriptional response of androgen-sensitive Levator ani muscle (LA) during atrophy reversion. Most of the differentially expressed genes behaved as atrogenes and responded to castration-induced atrophy. However, seven genes (APLN, DUSP5, IGF1, PIK3IP1, KLHL38, PI15, and MKL1) did not respond to castration but instead responded exclusively to testosterone replacement. Considering that almost all proteins encoded by these genes are associated with the reversion of atrophy and may function as regulators of cell proliferation/growth, our results provide new perspectives on the existence of anti-atrogenes.

Simple Summary The demands of modern society have made shift work a necessity. Night work is associated with an increased risk of metabolic problems such as obesity and diabetes, which is mainly due to the misalignment of circadian rhythms that play a crucial role in many biological processes. This study performed clinical, anthropometric, and molecular analyses on 40 hospital workers who work day or night. We demonstrated that night workers had increased glucose levels, triglycerides, waist circumference, and blood pressure compared to day workers. Surprisingly, we report that night workers have significant changes in the expression of circadian clock genes and an up-regulation of genes related to endoplasmic reticulum stress (ERS). These findings provide new insights into the effects of night shift work on the expression of circadian cycle genes and ERS activation, leading to metabolic stress and the development of metabolic diseases associated with night work. Abstract 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.

SAMHD1 (Sterile alpha motif and histidine-aspartic acid (HD) domain containing protein 1) is a deoxyribonucleoside triphosphate (dNTP) triphosphohydrolase (dNTPase) that restricts viral replication in infected cells. This protein is also involved in DNA repair by assisting in DNA end resection by homologous recombination (HR) after DNA double-strand break (DSB) induction with camptothecin (CPT) or etoposide (ETO). We showed that a monoclonal anti-SAMHD1 antibody produced against the full-length protein detected an unspecific 50 kDa protein that colocalized with dot-like structures after CPT treatment in HeLa cells. In contrast, a polyclonal anti-SAMHD1 antibody raised against the N-terminus of this protein specifically detected SAMHD1, as shown in Jurkat, HAP1KO and HEK293T SAMHD1-siRNA cell lysates compared with their respective controls. Our findings showed that SAMHD1 is not localized in dot-like structures under DSB induction in HeLa cells.

The FBXO25 mediates degradation of ELK-1 and thus inhibits transcriptional activation of immediate early genes (iEG). Here we show that FBXO25 regulates yet another node of this signaling pathway, by decreasing MAPK/ERK activity. We show that induction of FBXO25 reduced ERK1/2 phosphorylation independently of MEK1/2. Accordingly, in HAP1 FBXO25 knockout cells (FBXO25KO), we observed that upon PMA treatment ERK1/2 was more active than in parental cells. An increase in cell proliferation under receptor mediated activation of the ERK signaling pathway in FBXO25KO cells was also observed. Taken together we show that FBXO25 functions as a negative regulator of MAPK signaling though the reduction of ERK1/2 activation.