[The cell cycle pathway regulates chicken abdominal fat deposition as revealed by transcriptome sequencing].

With the improvement of growth traits and feed conversion rate, the abdominal fat rate of Chinese local breeds of broilers has been increasing. Excessive abdominal fat deposition not only reduces the slaughter rate and disease resistance of broiler chickens, but also produces waste due to the difficulty of fat treatment. In order to study the regulatory genes and pathways involved in abdominal fat deposition of broilers, we used high-fat diets to feed the Xinghua Chicken, which is a Chinese local breed. Two weeks after feeding, we found that the abdominal fat weight and rate of broilers in the high-fat diet group increased significantly, and the diameter and area of abdominal fat cells also increased significantly. Transcriptome sequencing of abdominal fat and livers showed that the differentially expressed genes in the abdominal fat were mainly enriched in the cell cycle, peroxisome proliferator- activated receptor (PPAR) and extracellular matrix (ECM) receptor signaling pathways. The differentially expressed genes in livers were also significantly enriched in the cell cycle pathway, as well as in the steroid biosynthesis and PPAR signaling pathway. By analyzing the common differentially expressed genes in abdominal fat and liver tissues, we found that these genes were also enriched in cell cycle. Finally, we used the chicken LMH (chicken hepatoma cell) cell line and chicken ICP (immortalized chicken preadipocytes) cell line to do the in vitro validation assays. We used high-fat and common medium to culture the cells. The results showed that after 48 hours, the high-fat medium could significantly promote cell cycle and increase the number of cells in S phase. Additionally, qRT-PCR results showed that the high-fat medium could significantly promote the expression of genes related to cell cycle. In conclusion, we found that high-fat diets activate the cell cycle progression of chicken hepatocytes and preadipocytes, promote cell proliferation, and then increase abdominal fat deposition.

Effects of lifestyle interventions on rural patients with type 2 diabetes mellitus.

BACKGROUND: The prevalence of type 2 diabetes mellitus (T2DM) is rising rapidly in rural areas, and lifestyle interventions can effectively reduce the blood glucose levels of patients with T2DM. However, current dietary and exercise guidelines are still at experimental stages and are difficult for subjects to understand and implement. The Human Metabolism Analyzer provides real life interventions for the prevention and treatment of T2DM, and our pilot research has demonstrated its effectiveness and good compliance. AIM: To investigate the effect of and compliance with lifestyle interventions in rural patients with T2DM. METHODS: A total of ten rural villages were randomly selected in Chaoshui Township, Penglai City, Shandong Province, China, to conduct health screening among residents aged 50 years or older. Each rural village represented a group, and 12 patients with T2DM were randomly selected from each group (total: 120) to participate in this study and receive real life lifestyle interventions and medication guidance. Lifestyle interventions included changing the meal order (A), postprandial activities (B), resistance exercise (C), and reverse abdominal breathing (D). Diabetes education was conducted at least once a month with a weekly phone follow-up to monitor exercise and diet. Waist circumference, blood pressure, body mass index (BMI), motor function, body composition, fasting blood glucose, and glycated hemoglobin (HbA1c) were analyzed before and 3 mo after the intervention. Moreover, patient compliance and adjustments of hypoglycemic drugs were evaluated. RESULTS: A total of 109 subjects completed the study. The compliance rates for lifestyle interventions A, B, C, and D were 57.79%, 60.55%, 64.22%, and 75.23%, respectively. Among the subjects who received hypoglycemic drugs, the dose was reduced 2 to 3 times based on blood glucose in 54 (67.50%) subjects and was tapered and discontinued in 5 (6.25%) subjects within 3 mo, with no significant fluctuations in blood glucose after dose reduction and withdrawal. After lifestyle interventions, waist circumference, BMI, fasting blood glucose, and HbA1c significantly decreased (P < 0.001); motor function and body composition also significantly improved (P < 0.001). CONCLUSION: For patients with T2DM, compliance to real-life lifestyle interventions is good, and the interventions significantly improve metabolic indicators such as waist circumference, BMI, blood pressure, HbA1c, body composition, and motor function. Some patients are able to taper or discontinue hypoglycemic drugs.

An Inframe Trinucleotide Deletion in MTRR Exon 1 is Associated with the Risk of Spina Bifida.

Maternal genetic variants of enzymes in folate-homocysteine metabolic network are significantly correlative with the risk of spina bifida. To survey the genetic causality, the genotypes of three women having spina bifida fetuses from two unrelated Chinese families were screened in candidate alleles. Polymerase chain reaction, capillary electrophoresis and Sanger sequencing were employed to recognize the allelic variation. A trinucleotide deletion (c.4_6delAGG) was identified in the first exon of MTRR. All the three women showed the novel clinical variation including one heterozygous and two homozygous. The siblings who had healthy babies from the same families did not harbor the variation. In the unaffected control individuals, the variant was also not observed. Eukaryotic expression and bioinformatics techniques were utilized to explore the molecular pathogenesis of the potential genetic risk of developing spina bifida. Exceptionally, the functional examination revealed that the Arg2del variant kept subcellular localization unaltered with catalytic activity intact, but failed to efficiently activate MTR compared with the wild type. Genetic disorder of folate and homocysteine metabolism during pregnancy is believed to be associated with folate-sensitive neural tube defects. The report highlights that the inframe deletion in MTRR exon 1 could be a high risk factor susceptibility to spina bifida.

Rich1 negatively regulates the epithelial cell cycle, proliferation and adhesion by CDC42/RAC1-PAK1-Erk1/2 pathway.

Rich1, a previously identified Rho GTPase-activating protein (RhoGAP), was found to have close relationship with Rho GTPase family members in multiple cellular processes in nervous cells and platelets. But the exact role of Rich1 in epithelial cells remains obscure. The present investigation demonstrated that up-regulation of Rich1 could cause S-phase arrest, proliferation inhibition and adhesion decline with F-actin amount decrease in epithelial cells. Further exploration in hepatocyte HL7702 revealed that overexpression of Rich1 could greatly elevate the intrinsic GTPase activities on both of CDC42 and RAC1 by stimulating GTP hydrolysis, which consequently attenuated the activities of the Rho proteins and the phosphorylation level of those in PAK1-ERK1/2 signaling cascade. While the GAP domain deleted Rich1 variant or silence of endogenous Rich1 expression could not result in any of the biological effects. It is indicated that Rich1, completely different from in other types of cells, might act as a crucial upstream negative regulator via its GAP domain in control of epithelial cell cycle, proliferation and focal adhesion through CDC42/RAC1-PAK1-ERK1/2 signaling pathway and F-actin dynamics.