Insulin sensitivity and metabolic flexibility decrease in response to bed rest, but the temporal and causal adaptations in human skeletal muscle metabolism are not fully defined. Here, we use an integrative approach to assess human skeletal muscle metabolism during bed rest and provide a multi-system analysis of how skeletal muscle and the circulatory system adapt to short- and long-term bed rest (German Clinical Trials: DRKS00015677). We uncover that intracellular glycogen accumulation after short-term bed rest accompanies a rapid reduction in systemic insulin sensitivity and less GLUT4 localization at the muscle cell membrane, preventing further intracellular glycogen deposition after long-term bed rest. We provide evidence of a temporal link between the accumulation of intracellular triglycerides, lipotoxic ceramides, and sphingomyelins and an altered skeletal muscle mitochondrial structure and function after long-term bed rest. An intracellular nutrient overload therefore represents a crucial determinant for rapid skeletal muscle insulin insensitivity and mitochondrial alterations after prolonged bed rest.
From PLoS website: In general, dietary antigens are tolerated by the gut associated immune system. Impairment of this so-called oral tolerance is a serious health risk. We have previously shown that activation of the ligand-dependent transcription factor aryl hydrocarbon receptor (AhR) by the environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) affects both oral tolerance and food allergy. In this study, we determine whether a common plant-derived, dietary AhR-ligand modulates oral tolerance as well. We therefore fed mice with indole-3-carbinole (I3C), an AhR ligand that is abundant in cruciferous plants. We show that several I3C metabolites were detectable in the serum after feeding, including the high-affinity ligand 3,3´-diindolylmethane (DIM). I3C feeding robustly induced the AhR-target gene CYP4501A1 in the intestine; I3C feeding also induced the aldh1 gene, whose product catalyzes the formation of retinoic acid (RA), an inducer of regulatory T cells. We then measured parameters indicating oral tolerance and severity of peanut-induced food allergy. In contrast to the tolerance-breaking effect of TCDD, feeding mice with chow containing 2 g/kg I3C lowered the serum anti-ovalbumin IgG1 response in an experimental oral tolerance protocol. Moreover, I3C feeding attenuated symptoms of peanut allergy. In conclusion, the dietary compound I3C can positively influence a vital immune function of the gut.
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Knowledge of the time of deposition is pivotal in forensic investigations. Recent studies show that changes in intrinsic fluorescence over time can be used to estimate the age of body fluids. These changes have been attributed to oxidative modifications caused by protein–lipid interactions. This pilot study aims to explore the impact of these modifications on body fluid fluorescence, enhancing the protein–lipid model system for age estimation. Lipid and protein oxidation markers, including protein carbonyls, dityrosine, advanced glycation end-products (AGEs), malondialdehyde (MDA), and 4-hydroxynonenal (HNE), were studied in aging semen, urine, and saliva over 21 days. Surface plasmon resonance imaging (SPRi), enzyme-linked immunosorbent assay (ELISA), and fluorescence spectroscopy were applied. Successful detection of AGE, dityrosine, MDA, and HNE occurred in semen and saliva via SPRi, while only dityrosine was detected in urine. Protein carbonyls were measured in all body fluids, but only in saliva was a significant increase observed over time. Additionally, protein fluorescence loss and fluorescent oxidation product formation were assessed, showing significant decreases in semen and saliva, but not in urine. Although optimization is needed for accurate quantification, this study reveals detectable markers for protein and lipid oxidation in aging body fluids, warranting further investigation.
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