Insulin Signaling in Liver and Adipose Tissues in Periparturient Dairy Cows Supplemented with Dietary Nicotinic Acid

The glucose homeostasis in dairy cattle is very well controlled, in line with the metabolic adaptation during the periparturient period. Former studies showed that nicotinic acid (NA) lowered plasma non-esterified fatty acids (NEFA) concentrations and increased insulin sensitivity in dairy cows. Thus, the purpose of this study was to investigate whether the expression of proteins involved in hepatic and adipose insulin signaling and protein expression of hepatic glucose transporter 2 (GLUT2) were affected by dietary NA and dietary concentrate intake in periparturient dairy cows. Twenty pluriparous German Holstein cows were fed with the same diet from about 21 days before the expected calving date (d-21) to calving. After calving, cows were randomly assigned in 4 groups and fed with diets different in concentrate proportion ("HC" with 60:40% or "LC" with 30:70% concentrate-to-roughage ratio) and supplemented with NA (24 g/day) (NA) or without (CON) until d21. Biopsy samples were taken from the liver, subcutaneous (SCAT) and retroperitoneal (RPAT) adipose tissues at d-21 and d21. Protein expression of insulin signaling molecules (insulin receptor (INSR), phosphatidylinositol-3-kinase (PI3K), protein kinase C zeta (PKC zeta)) and hepatic GLUT2 was measured by Western Blotting. The ratio of protein expression at d21/at d-21 was calculated and statistically evaluated for the effects of time and diet. Cows in HC had significantly higher dietary energy intake than cows in LC. In RPAT a decrease in PI3K and PKC zeta expression was found in all groups, irrespectively of diet. In the liver, the GLUT2 expression was significantly lower in cows in NA compared with cows in CON. In conclusion, insulin signaling might be decreased in RPAT over time without any effect of diet. NA was able to modulate hepatic GLUT2 expression, but its physiological role is unclear

Associations between Forkhead Box O1 (FoxO1) Expression and Indicators of Hepatic Glucose Production in Transition Dairy Cows Supplemented with Dietary Nicotinic Acid

Forkhead box protein O1 (FoxO1) is a transcription factor which promotes hepatic glucose production (HGP) by up-regulating the transcription of gluconeogenic enzymes in monogastric species. The activity of FoxO1 is inhibited by insulin-induced phosphorylation. The aims of the present study were to find associations between FoxO1 expression and variables associated with HGP as affected by feeding regimen in dairy cows during the transition period. Twenty one healthy German Holstein cows were allocated to four groups (LC-CON, HC-CON, LC-NA with 5 cows/group and HC-NA with 6 cows/group, respectively). Cows received 0 (LC-CON and HC-CON) or 24 (LC-NA and HC-NA) g/d nicotinic acid with high (HC) or low (LC) concentrate proportion from -42 days (-41.8 + 4.8;mean + standard deviation) relative to expected calving date (d-42) to d24. Liver biopsy was taken at d-42, 1, 21, and 100. The total protein expression of FoxO1 (tFoxO1) and the extent of phosphorylation of FoxO1 at serine 256 (pFoxO1) were analysed semiquantitatively by Western Blotting. The expression of hepatic mRNA of FoxO1 and seven genes associated with HGP was measured by real-time RT-PCR. Mixed model and Pearson's correlation were used for statistical evaluation with the level of significance at P<0.05. No dietary effect was observed either on feed intake, energy balance, or on the concentration of blood metabolites. Neither time nor diet affected the expression of FoxO1 total protein and mRNA. A NA x concentrate interaction was found in pFoxO1. However, no corresponding dietary effect was found in the mRNA expression of investigated genes. Different patterns of correlations between FoxO1-related variables and investigated indicators for HGP were found at d21 and 100. The results indicated that the regulation of HGP did not take place on the levels of mRNA and protein expression and the phosphorylation of FoxO1 in dairy cows in early lactation

マウスの胸腺と脾臓におけるIgE転写の比較

1週齢から5週齢BALB/cマウスの抗体遺伝子の転写を,胸腺と脾臓で比較した。調べた抗体のクラスのなかで,IgEの転写量に関しては,胸腺と脾臓で明瞭な差異が認められた。胸腺では,雌雄ともに,IgEは1週齢から転写されていた。脾臓では3週齢までは検出できなかった。雌では,3週齢から4週齢の間で,脾臓でもIgEの転写が検出され始めた。雄では,5週齢まででは,脾臓でIgEの転写は検出できなかった。IgEの転写に関して胸腺と脾臓で明瞭な差異が認められることから,胸腺で抗体遺伝子を転写している細胞は,胸腺内の血管内のBリンパ球ではなく,また,脾臓で分化したBリンパ球が流入したものでもなく,発生段階で流入した幹細胞から胸腺内で分化したリンパ球であると考えられる。Immunoglobulin heavy chain gene transcription was investigated by reverse transcription PCR both in the thymus and in the spleen of BALB/c mice of age 1 to 5 weeks old. A definitive difference in IgE transcriptions was found between in the thymus and in the spleen. IgE transcriptions were demonstrated clearly in the thymus of all mice, while, in the spleen, not detected in 1 to 3 weeks old. Therefore, the cells transcribing antibody genes in the thymus of mouse are neither B lymphocytes in blood vessels, nor invaded B lymphocytes after proliferation and development in the spleen. Those will be specific cells which proliferate and develop in the thymus from stem cells which immigrated at embryonic stage

Severity of Depressive Symptoms and Volume of Superior Temporal Gyrus in People Who Visit a Memory Clinic Unaccompanied

Background/Aims: Depression and cognitive decline are reported to be interrelated. Depression of older adults with memory complaints who seek medical help have not been well documented. This study was carried out to test the hypothesis that a relatively high level of depressive symptoms associated with brain structure is characteristic of people who visited a memory clinic unaccompanied (UA). Method: We retrospectively compared Center for Epidemiologic Studies Depression Scale (CES-D, for evaluation of depressive symptoms) scores of UA subjects (n = 21) with those of people who were accompanied (n = 75). Within each groups, we further examined the association between brain morphology and the CES-D scores using FreeSurfer software. Results: We found that the relatively high CES-D scores of UA subjects were inversely associated with the normalized volumes of bilateral superior temporal gyrus (STG). Conclusion: Our results suggest that depressive symptoms of UA subjects demonstrated by the relatively high levels of CES-D scores were primary, because of the inverse association with the normalized volume of bilateral STG. Thus, focusing on the depressive symptoms may be a suitable approach to satisfy potential medical needs of UA subjects with or without memory impairment

Chronic Effects of Fusarium Mycotoxins in Rations with or without Increased Concentrate Proportion on the Insulin Sensitivity in Lactating Dairy Cows

The objective of this study was to investigate the effect of long-term exposure to a Fusarium toxin deoxynivalenol (DON, 5 mg/kg DM) on the energy metabolism in lactating cows fed diets with different amounts of concentrate. In Period 1 27 German Holstein cows were assigned to two groups and fed a control or mycotoxin-contaminated diet with 50% concentrate for 11 weeks. In Period 2 each group was further divided and fed either a diet containing 30% or 60% concentrate for 16 weeks. Blood samples were collected in week 0, 4, 8, 15, 21, and 27 for calculation of the Revised Quantitative Insulin Sensitivity Check Index and biopsy samples of skeletal muscle and the liver in w 0, 15, and 27 for analysis by real-time RT-qPCR. The DON-fed groups presented lower insulin sensitivities than controls at week 27. Concomitantly, muscular mRNA expression of insulin receptors and hepatic mRNA expression of glucose transporter 2 and key enzymes for gluconeogenesis and fatty acid metabolism were lower in DON-fed cows compared to the control. The study revealed no consistent evidence that DON effects were modified by dietary concentrate levels. In conclusion, long-term dietary DON intake appears to have mild effects on energy metabolism in lactating dairy cows