Neuroprotective Mechanism of MOTS-c in TBI Mice: Insights from Integrated Transcriptomic and Metabolomic Analyses.

Background: Traumatic brain injury (TBI) is a condition characterized by structural and physiological disruptions in brain function caused by external forces. However, as the highly complex and heterogenous nature of TBI, effective treatments are currently lacking. Mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) has shown notable antinociceptive and anti-inflammatory effects, yet its detailed neuroprotective effects and mode of action remain incompletely understood. This study investigated the neuroprotective effects and the underlying mechanisms of MOTS-c. Methods: Adult male C57BL/6 mice were randomly divided into three groups: control (CON) group, MOTS-c group and TBI group. Enzyme-linked immunosorbent assay (ELISA) kit method was used to measure the expression levels of MOTS-c in different groups. Behavioral tests were conducted to assess the effects of MOTS-c. Then, transcriptomics and metabolomics were performed to search Differentially Expressed Genes (DEGs) and Differentially Expressed Metabolites (DEMs), respectively. Moreover, the integrated transcriptomics and metabolomics analysis were employed using R packages and online Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Results: ELISA kit method showed that TBI resulted in a decrease in the expression of MOTS-c. and peripheral administration of MOTS-c could enter the brain tissue after TBI. Behavioral tests revealed that MOTS-c improved memory, learning, and motor function impairments in TBI mice. Additionally, transcriptomic analysis screened 159 differentially expressed genes. Metabolomic analysis identified 491 metabolites with significant differences. Integrated analysis found 14 KEGG pathways, primarily related to metabolic pathways. Besides, several signaling pathways were enriched, including neuroactive ligand-receptor interaction and retrograde endocannabinoid signaling. Conclusion: TBI reduced the expression of MOTS-c. MOTS-c reduced inflammatory responses, molecular damage, and cell death by down-regulating macrophage migration inhibitory factor (MIF) expression and activating the retrograde endocannabinoid signaling pathway. In addition, MOTS-c alleviated the response to hypoxic stress and enhanced lipid ß-oxidation to provide energy for the body following TBI. Overall, our study offered new insights into the neuroprotective mechanisms of MOTS-c in TBI mice.

Epigenetic Regulation of Autophagy in Bone Metabolism.

The skeletal system is crucial for supporting bodily functions, protecting vital organs, facilitating hematopoiesis, and storing essential minerals. Skeletal homeostasis, which includes aspects such as bone density, structural integrity, and regenerative processes, is essential for normal skeletal function. Autophagy, an intricate intracellular mechanism for degrading and recycling cellular components, plays a multifaceted role in bone metabolism. It involves sequestering cellular waste, damaged proteins, and organelles within autophagosomes, which are then degraded and recycled. Autophagy's impact on bone health varies depending on factors such as regulation, cell type, environmental cues, and physiological context. Despite being traditionally considered a cytoplasmic process, autophagy is subject to transcriptional and epigenetic regulation within the nucleus. However, the precise influence of epigenetic regulation, including DNA methylation, histone modifications, and non-coding RNA expression, on cellular fate remains incompletely understood. The interplay between autophagy and epigenetic modifications adds complexity to bone cell regulation. This article provides an in-depth exploration of the intricate interplay between these two regulatory paradigms, with a focus on the epigenetic control of autophagy in bone metabolism. Such an understanding enhances our knowledge of bone metabolism-related disorders and offers insights for the development of targeted therapeutic strategies.

Assessment of cold exposure-induced metabolic changes in mice using untargeted metabolomics.

Background: Cold exposure (CE) can effectively modulate adipose tissue metabolism and improve metabolic health. Although previous metabolomics studies have primarily focused on analyzing one or two samples from serum, brown adipose tissue (BAT), white adipose tissue (WAT), and liver samples, there is a significant lack of simultaneous analysis of multiple tissues regarding the metabolic changes induced by CE in mice. Therefore, our study aims to investigate the metabolic profiles of the major tissues involved. Methods: A total of 14 male C57BL/6J mice were randomly assigned to two groups: the control group (n = 7) and the CE group (n = 7). Metabolite determination was carried out using gas chromatography-mass spectrometry (GC-MS), and multivariate analysis was employed to identify metabolites exhibiting differential expression between the two groups. Results: In our study, we identified 32 discriminant metabolites in BAT, 17 in WAT, 21 in serum, 7 in the liver, 16 in the spleen, and 26 in the kidney, respectively. Among these metabolites, amino acids, fatty acids, and nucleotides emerged as the most significantly altered compounds. These metabolites were found to be associated with 12 differential metabolic pathways closely related to amino acids, fatty acids, and energy metabolism. Conclusion: Our study may provide valuable insights into the metabolic effects induced by CE, and they have the potential to inspire novel approaches for treating metabolic diseases.