phosphothreonine and Body-Weight

Studies have shown that the removal of the cholinergic innervation to the hippocampus induces dysfunction of the hypothalamic-pituitary-adrenocortical axis and decreases the number of glucocorticoid receptors (GRs). Subsequent studies have revealed that the loss of cholinergic input to the hippocampus reduces the expression of GRs and activates nuclear factor-kappa B (NF-κB) signaling through interactions with the cytoplasmic catalytic subunit of protein kinase A (PKAc). We examined the effects of chronic stress on cognitive status and GR-PKAc-NF-κB signaling in rats with a loss of cholinergic input to the hippocampus and cortex. Male Sprague-Dawley rats received 192 IgG-saporin injections to selectively eliminate cholinergic neurons in their basal forebrain. Two weeks later, rats were subjected to 1 h of restraint stress per day for 14 days. Rats subjected to both chronic stress and cholinergic depletion showed more severe memory impairments compared to those that received either treatment alone. The reduction in nuclear GR levels induced by cholinergic depletion was unaffected by chronic stress. The activation of NF-κB signaling in the hippocampus and the cerebral cortex induced by cholinergic depletion was augmented by chronic stress, resulting in the increased expression of pro-inflammatory markers, such as inducible nitric oxide synthase and cyclooxygenase-2. The activation of NF-κB induced by cholinergic depletion appears to be aggravated by chronic stress, and this might explain the increased susceptibility of patients with Alzheimer's disease to stress since activation of NF-κB is associated with stress.

Topics: Animals; Body Weight; Cerebral Cortex; Choline O-Acetyltransferase; Cholinergic Neurons; Corticosterone; Cyclic AMP-Dependent Protein Kinases; Cyclooxygenase 2; Hippocampus; Male; Memory; NF-kappa B; Nitric Oxide Synthase Type II; Phosphorylation; Phosphothreonine; Rats, Sprague-Dawley; Receptors, Glucocorticoid; Reproducibility of Results; Signal Transduction; Spatial Learning; Stress, Psychological

This study investigated the molecular effects of acylated (AG) and unacylated ghrelin (UAG) or their combination on hepatic lipogenesis pathways and DAG/PKC/JNK signaling in the livers of lean rats fed standard diet. Male rats (n = 10) were classified as control + vehicle (saline, 200 μl), AG, UAG, and AG + UAG-treated groups. All treatments were given at final doses of 200 ng/kg of for 14 days (twice/day, S.C). Administration of AG significantly enhanced circulatory levels of AG and UAG turning the normal ratio of AG/UAG from 1:2.5 to 1:1.2. However, while UAG didn't affect circulatory levels of AG, administration of UAG alone or in combination with AG resulted in AG/UAG ratios of 1:7 and 1:3, respectively. Independent of food intake nor the development of peripheral IR, AG increased hepatic DAG, TGs and CHOL contents and induced hepatic IR. Mechanism of action include 1) upregulation of mRNA and protein levels of DGAT-2 and mtGPAT-1, SREBP-1 and SCD-1, and 2) inhibition of fatty acids (FAs) oxidation mediated by inhibition of AMPK/ PPAR-α/CPT-1 axis. Consequently, AG induced membranous translocation of PKCδ and PKCε leading to activation of JNK and significant inhibition of insulin signaling under basal and insulin stimulation as evident by decreases in the phosphorylation levels of IRS (Tyr

Topics: Acylation; Animals; Blood Glucose; Body Weight; Diglycerides; Fatty Liver; Gene Expression Regulation; Ghrelin; Hepatocytes; Insulin; Insulin Resistance; JNK Mitogen-Activated Protein Kinases; Liver; Male; Phosphorylation; Phosphothreonine; Protein Kinase C; Protein Transport; Rats, Wistar; RNA, Messenger; Signal Transduction; Thinness