黑龙江中医药大学

Metabolic dysfunction-associated steatotic liver disease (MASLD), whose pathogenesis involves complex multi-organ crosstalk and the remodeling of the hepatic immune microenvironment, constitutes a major global health challenge. The latest research indicates that the dysregulation of the AMPK-SREBP1-FASN (ASF) signaling axis plays a core role in mediating abnormal fatty acid synthesis and the accumulation of lipotoxic metabolites in MASLD, serving as a key molecular hub linking hepatic metabolic disorders with immune inflammatory responses. Dysregulated ASF axis and the subsequent lipotoxic products not only directly impair hepatocellular organelle function but also, by disrupting intercellular communication and reprogramming immune cell and hepatocyte metabolism, drive a self-perpetuating “metabolic-immune” vicious cycle. This cycle propels disease progression toward fibrosis and extrahepatic complications. However, how ASF axis dysregulation specifically reshapes the hepatic immune landscape remains to be systematically elucidated. This review aims to systematically describe the crucial role of the ASF axis in MASLD. First, it outlines the pivotal function of this axis in multi-system interactions and the disruption of the hepatic immune microenvironment. It then provides an in-depth analysis of the regulatory mechanisms and functional characteristics of the ASF axis in both hepatocytes and immune cells. Furthermore, it explores the molecular mechanisms by which ASF axis dysregulation exacerbates lipotoxicity through promoting CD36-dependent lipid uptake and dissects how lipotoxicity impairs hepatocellular function and hepatic immune homeostasis in MASLD. Finally, the review summarizes potential therapeutic strategies targeting the ASF axis, which are designed to disrupt the metabolic-immune vicious cycle and restore systemic homeostasis. By offering an integrated perspective, this review seeks to advance the understanding of the immune-metabolic pathogenesis of MASLD and to establish a theoretical foundation for developing precise therapeutic interventions.

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s40359-024-01628-6.

Processing is the core traditional technology to regulate the efficacy of traditional Chinese medicine. Polysaccharides serve as key components in exerting biological activities such as immune regulation, antioxidant, and blood sugar reduction, its content and structural characteristics determine its biological activity, therefore, clarifying the mechanism by which processing affects the polysaccharides in traditional Chinese medicine is an important direction for explaining the processing of traditional Chinese medicine. In this paper, the main processing methods such as stir-frying, roasting and steaming are arranged and expounded in detail in terms of content, structure and activity. The results indicate that the processing affects the polysaccharide content through changing the physical properties of herbs, damaging cell structures, and triggering chemical reactions through multiple pathways. By breaking glycosidic bonds under the action of heat, acid and water, the changes of molecular weight, monosaccharide composition, functional group ratio and the spatial structure of polysaccharide were changed, thus affecting the biological activities of polysaccharide such as immunity and antioxidation. The existing research shows that the effect of processing on traditional Chinese medicine polysaccharide has the specificity of “process-medicine-component”, in the future, modern analytical techniques such as X-ray diffraction and high-resolution mass spectrometry should be combined to deeply analyze the molecular mechanism of regulating the structure-activity relationship of polysaccharides in processing, so as to provide scientific basis for the standardization and accurate optimization of processing technology of traditional Chinese medicine.

Diabetic cardiomyopathy (DCM) is one of the crucial causes leading to heart failure and adverse outcomes in patients with diabetes mellitus; however, effective strategies targeting its molecular pathological mechanisms and therapies are currently lacking. DCM is primarily characterized by early diastolic dysfunction, cardiomyocyte apoptosis, and fibrosis. Its disease progression is relatively insidious, eventually evolving into heart failure with preserved ejection fraction. The intrinsic metabolic environment of diabetes markedly exacerbates oxidative stress, and the accumulated polyunsaturated fatty acids within cardiomyocytes are highly susceptible to lipid peroxidation, leading to the excessive generation of 4-hydroxy-2-nonenal (4-HNE). The pivotal role of this reactive aldehyde in promoting the progression of DCM has been extensively demonstrated in animal, cellular, and clinical models. However, its subcellular targets and the underlying molecular mechanisms remain inadequately elucidated. Organelles, as central executors of diverse intracellular functions, may serve as potential sites of 4-HNE-induced interference and therapeutic targeting. This article focuses on the central role of 4-HNE in triggering energy depletion, calcium overload, autophagic flux blockade, and ferroptosis through its interactions among mitochondria, endoplasmic reticulum, lysosomes, and other organelles. On the basis of existing evidence, potentially translatable therapeutic avenues include ALDH2 activators, G protein–coupled receptor 40 (GPR40) agonists, mitochondria-targeted antioxidants and ferroptosis inhibitors. The aim is to provide a theoretical foundation and reference for the clinical identification of myocardial injury in DCM, model replication, and the development of targeted intervention strategies.

Adipose tissue thermogenesis has emerged as a prominent research focus for the treatment of metabolic diseases, particularly through mitochondrial uncoupling, which oxidizes nutrients to produce heat rather than synthesizing ATP. Uncoupling protein 1 (UCP1) has garnered significant attention as a core protein mediating non-shivering thermogenesis(NST). However, recent studies indicate that energy dissipation can also occur via UCP1-independent thermogenesis, partially driven by futile metabolic cycles. These cycles involve ATP depletion coupled with reversible energy reactions, resulting in futile energy expenditure. Unlike classical UCP1-mediated thermogenesis, futile cycling is not confined to brown and beige adipose tissue, suggesting a broader range of therapeutic targets. These findings open new avenues for targeting these pathways to enhance metabolic health. This review explores the characteristics and distinctions of the primary metabolic organs (adipose tissue, liver, and skeletal muscle) involved in the futile cycles of thermogenesis. It further elaborates on the cellular and molecular mechanisms underlying calcium, creatine, and lipid cycling, emphasizing their strengths, limitations, and roles beyond thermogenesis.