The metabolism of glucose and lipids is essential for energy production in the body, and dysregulation of the metabolic pathways of these molecules is implicated in various acute and chronic diseases, such as type 2 diabetes, Alzheimer’s disease, atherosclerosis (AS), obesity, tumor, and sepsis. Post-translational modifications (PTMs) of proteins, which involve the addition or removal of covalent functional groups, play a crucial role in regulating protein structure, localization function, and activity. Common PTMs include phosphorylation, acetylation, ubiquitination, methylation, and glycosylation. Emerging evidence indicates that PTMs are significant in modulating glucose and lipid metabolism by modifying key enzymes or proteins. In this review, we summarize the current understanding of the role and regulatory mechanisms of PTMs in glucose and lipid metabolism, with a focus on their involvement in disease progression associated with aberrant metabolism. Furthermore, we discuss the future prospects of PTMs, highlighting their potential for gaining deeper insights into glucose and lipid metabolism and related diseases.

Non-coding RNA: a potential biomarker and therapeutic target for sepsis Non-coding RNA: a potential biomarker and therapeutic target for sepsis

Myocardial injury resulting from sepsis is the leading cause of death worldwide. Micro RNA miR-122-5p is involved in various physiological and pathological processes and is highly expressed in the heart of septic rats. However, its function in sepsis-caused myocardial injury remains elusive. Herein, a rat model of septic myocardial injury was established by intraperitoneal injection of lipopolysaccharide (LPS), and cardiomyocyte H9c2 was exposed to LPS to induce sepsis-related inflammatory injury in vitro. Inhibition of miR-122-5p suppressed LPS-triggered myocardial injury evidenced by decreased heart weight index (HWI), reduced inflammatory cell infiltration and cell rupture, and reduced cardiac marker enzymes cTnI and LDH. MiR-122-5p inhibition inhibited ROS production and enhanced the activities of antioxidant enzymes CAT, SOD and GSH-px in LPS-treated rats and H9c2 cells. MiR-122-5p inhibition reduced the production of pro-inflammatory cytokines TNF-α, IL-6 and IL-1β, and inhibited cell apoptosis along with decreased cleaved-caspase 3 induced by LPS. Moreover, increased GIT1 expression was found following miR-122-5p inhibition. We further verified GIT1 as a target of miR-122-5p, and silencing GIT1 partially reversed the benefits of miR-122-5p loss in LPS-injured H9c2 cells. The HO-1 and NQO-1 expression and Nrf-2 activation were enhanced by miR-122-5p inhibition, which was reversed by GIT1 depletion, indicating the involvement of Nrf-2/HO-1 signaling in regulating miR-122-5p/GIT1-mediated cardioprotection. Taken together, our data suggest that inhibition of miR-122-5p may mitigate sepsis-triggered myocardial injury through inhibiting inflammation, oxidative stress and apoptosis via targeting GIT1, which provides a possible therapeutic target for sepsis. GRAPHICAL ABSTRACT

BACKGROUND: Serum lactate levels are used to evaluate tissue hypoxia and predict outcomes in cases of sepsis and septic shock. Lactate can participate in a posttranslational modification known as lactylation. Myocardial depression during sepsis and septic shock is common. Here, we investigated the role of lactate in sepsis-induced myocardial depression. METHODS: Septic myocardial depression in rats was induced by lipopolysaccharide administration or cecal ligation and puncture. Lactylation and protein profiles of heart tissues from the control and lipopolysaccharide groups were analyzed using proteomic analysis. Lactylation of the HADHA (trifunctional enzyme subunit alpha) at K166 and K728 was detected in septic heart tissues and lipopolysaccharide-induced cultured cells. Mutation of K166 and K728 HADHA were used to clarify the effects of HADHA lactylation on mitochondrial function, ATP production, energy metabolism, and heart function. Transcriptomic and metabolomic analyses were used to identify differentially expressed genes and differential metabolites in H9c2 (rat cardiomyoblast cell line) cells. RESULTS: We identified 1127 lysine lactylation sites, with 83 differentially lactylated lysine sites. By integrating multifeature hybrid learning and protein language models, we identified lactylation at K166 and K728 of the HADHA as functionally important. We confirmed that lactylation at these sites was influenced by lactate levels and inhibited the HADHA activity, which disturbed mitochondrial function, ATP production, and energy metabolism. This reduction in the contraction force of cardiomyocytes can influence heart function in vitro and in vivo. Furthermore, this study revealed that sirtuin 1 and sirtuin 3 regulated the lactylation of HADHA at K166 and K728. CONCLUSIONS: This study reveals the significant impact of lactylation on cardiomyocyte metabolism. Lactate-induced HADHA lactylation disturbs cardiomyocyte mitochondrial function and metabolism and promotes sepsis-induced cardiac dysfunction. These findings inform the development of new therapeutic targets for sepsis-induced myocardial depression.

Long non-coding RNAs (lncRNAs) are a type of non-coding RNA with a length that exceeds 200 nucleotides. Previous studies have shown that lncRNAs play an important role in the pathogenesis of various diseases. Research in both animal models and humans has begun to unravel the profound complexity of lncRNAs and demonstrated that lncRNAs exert direct effects on glucose and lipid metabolism both in vivo and in vitro. Such research has elucidated the regulatory role of lncRNAs in glucose and lipid metabolism in human disease. lncRNAs mediate glucose and lipid metabolism under physiological and pathological conditions and contribute to various metabolism disorders. This review provides an update on our understanding of the regulatory role of lncRNAs in glucose and lipid metabolism in various diseases. As our understanding of the function of lncRNAs improves, the future is promising for the development of new diagnostic biomarkers that utilize lncRNAs and treatments that target lncRNAs to improve clinical outcomes.