Lactate is a byproduct of glycolysis, and before the Warburg effect was revealed (in which glucose can be fermented in the presence of oxygen to produce lactate) it was considered a metabolic waste product. At present, lactate is not only recognized as a metabolic substrate that provides energy, but also as a signaling molecule that regulates cellular functions under pathophysiological conditions. Lactylation, a post‑translational modification, is involved in the development of various diseases, including inflammation and tumors. Liver disease is a major health challenge worldwide. In normal liver, there is a net lactate uptake caused by gluconeogenesis, exhibiting a higher net lactate clearance rate compared with any other organ. Therefore, abnormalities of lactate and lactate metabolism lead to the development of liver disease, and lactate and lactate metabolism‑related genes can be used for predicting the prognosis of liver disease. Targeting lactate production, regulating lactate transport and modulating lactylation may be potential treatment approaches for liver disease. However, currently there is not a systematic review that summarizes the role of lactate and lactate metabolism in liver diseases. In the present review, the role of lactate and lactate metabolism in liver diseases including liver fibrosis, non‑alcoholic fatty liver disease, acute liver failure and hepatocellular carcinoma was summarized with the aim to provide insights for future research.

Although some clinical studies have reported increased mitochondrial respiration in patients with fatty liver and early non‑alcoholic steatohepatitis (NASH), there is a lack of in vitro models of non‑alcoholic fatty liver disease (NAFLD) with similar findings. Despite being the most commonly used immortalized cell line for in vitro models of NAFLD, HepG2 cells exposed to free fatty acids (FFAs) exhibit a decreased mitochondrial respiration. On the other hand, the use of HepaRG cells to study mitochondrial respiratory changes following exposure to FFAs has not yet been fully explored. Therefore, the present study aimed to assess cellular energy metabolism, particularly mitochondrial respiration, and lipotoxicity in FFA‑treated HepaRG and HepG2 cells. HepaRG and HepG2 cells were exposed to FFAs, followed by comparative analyses that examained cellular metabolism, mitochondrial respiratory enzyme activities, mitochondrial morphology, lipotoxicity, the mRNA expression of selected genes and triacylglycerol (TAG) accumulation. FFAs stimulated mitochondrial respiration and glycolysis in HepaRG cells, but not in HepG2 cells. Stimulated complex I, II‑driven respiration and β‑oxidation were linked to increased complex I and II activities in FFA‑treated HepaRG cells, but not in FFA‑treated HepG2 cells. Exposure to FFAs disrupted mitochondrial morphology in both HepaRG and HepG2 cells. Lipotoxicity was induced to a greater extent in FFA‑treated HepaRG cells than in FFA‑treated HepG2 cells. TAG accumulation was less prominent in HepaRG cells than in HepG2 cells. On the whole, the present study demonstrates that stimulated mitochondrial respiration is associated with lipotoxicity in FFA‑treated HepaRG cells, but not in FFA‑treated HepG2 cells. These findings suggest that HepaRG cells are more suitable for assessing mitochondrial respiratory adaptations in the developed in vitro model of early‑stage NASH.

Poor sleep raises the risk of non-alcoholic fatty liver disease (NAFLD) and hastens disease progression. It is critical to figure out what factors impact the sleep quality of NAFLD patients. The present study aimed to investigate the role of anxiety symptoms in accounting for the impact of rumination on sleep quality and the moderating role of resilience on the associations of rumination with anxiety symptoms and sleep quality.
In the cross-sectional study, 285 NAFLD patients completed the Chinese version of the Pittsburgh Sleep Quality Index, the Ruminative Responses Scale, the Generalized Anxiety Disorder 7-item scale, and the 14-item Resilience Scale to measure sleep quality, rumination (including brooding and reflection), anxiety symptoms, and resilience, respectively. The PROCESS macro for SPSS v4.0 procedure was applied to perform moderated mediation analysis.
The roles of anxiety symptoms in accounting for the positive associations of brooding, reflection and rumination with poor sleep quality were revealed. It was found that there was a significant moderating role of resilience on the positive associations of brooding, reflection and rumination with anxiety symptoms, which were gradually reduced as resilience increased. The direct associations between brooding, reflection and rumination and poor sleep quality were not significantly moderated by resilience. Thus, a moderated mediation model involving anxiety symptoms and resilience for explaining the impact of rumination on poor sleep quality was supported among patients with NAFLD.
Rumination (including brooding and reflection) could be positively related to poor sleep quality, and anxiety symptoms had a significant role in accounting for the relationship among patients with NAFLD. Resilience showed a moderating role that could attenuate the positive association between rumination and anxiety symptoms. Interventions aimed at alleviating rumination, reducing anxiety symptoms, and enhancing resilience could improve the sleep quality of NAFLD patients.

Non‑alcoholic fatty liver disease (NAFLD) is an increasingly prevalent ailment worldwide. Moreover, de novo lipogenesis (DNL) is considered a critical factor in the development of NAFLD; hence, its inhibition is a promising target for the prevention of fatty liver disease. There is evidence to indicate that AMP‑activated protein kinase (AMPK) and sirtuin 1 (SIRT1) may play a crucial role in DNL and are the regulatory proteins in type 2 diabetes mellitus, obesity and cardiovascular disease. Therefore, AMPK and SIRT1 may be promising targets for the treatment of NAFLD. The present review article thus aimed to summarize the findings of clinical studies published during the past decade that suggested the beneficial effects of AMPK and SIRT1, using their specific activators and their combined effects on fatty liver disease.

Non‑alcoholic fatty liver disease (NAFLD) is a clinically progressive illness that can advance from simple fatty liver to non-alcoholic hepatitis and liver fibrosis. Cirrhosis and hepatocellular carcinoma are two of the most common diseases caused by NAFLD. As there are no early disease biomarkers and no US Food and Drug Administration‑approved medications, treatment for NAFLD is still focused on altering lifestyle and dietary habits, which makes it difficult to treat effectively. As a result, a novel treatment is urgently needed to prevent NAFLD progression. Calcium (Ca2+) channels regulate intracellular Ca2+ homeostasis via the mediation of Ca2+ flow. Previous studies have reported that Ca2+ channel expression varies throughout the development and progression of NAFLD, which results in the dysregulation of intracellular Ca2+ homeostasis, endoplasmic reticulum stress, mitochondrial dysfunction and autophagy suppression, all of which contribute to NAFLD progression. Several types of Ca2+ channels (including two‑pore segment channel 2, transient receptor potential, inositol triphosphate receptor, voltage‑dependent anion channel 1, store‑operated Ca2+ entry, purinergic receptor X7 and potassium Ca2+‑activated channel subfamily N member 4) have been identified as potential targets for preventing NAFLD development and controlling intracellular Ca2+ homeostasis. To achieve this, these channels can be blocked or activated, which exerts anti‑steatotic, anti‑inflammatory, anti‑fibrotic and other effects, which ultimately prevents the development of NAFLD. In the present review NAFLD therapeutics and the treatments that target Ca2+ channels that are currently being developed were examined.

Non‑alcoholic fatty liver disease (NAFLD) has a high incidence, and can lead to liver cirrhosis and even hepatocellular carcinoma in severe cases. To the best of our knowledge, there is currently no safe and effective treatment for the management of this disease. Ginsenoside Rg1 (Rg1) is an active monomer derived from ginseng and notoginseng. In the present study, HHL‑5 hepatocytes were used to establish an in vitro cell model of NAFLD by medium‑ and long‑chain fat emulsion treatment, and the effects of Rg1 on adipose accumulation, apoptosis and the expression levels of apoptosis‑related proteins in HHL‑5 hepatocytes were examined. The results demonstrated that Rg1 inhibited the accumulation of fat in HHL‑5 cells, while inhibiting apoptosis, and Rg1 downregulated the expression levels of the pro‑apoptotic protein Bax and upregulated the expression levels of the anti‑apoptotic protein Bcl‑2, indicating that Rg1 could promote the stability or integrity of mitochondria and exert an anti‑apoptotic effect by regulating Bcl‑2 family proteins. In addition, Rg1 markedly downregulated the expression levels of sphingosine‑1‑phosphate lyase 1 (SGPL1), a key enzyme in the sphingosine signaling pathway, in HHL‑5 cells with steatosis, and increased the expression levels of the downstream pro‑survival signals phosphorylated (p‑)Akt and p‑Erk1/2. Furthermore, overexpression of SGPL1 abolished the anti‑apoptotic effect of Rg1 on SGPL1‑overexpressing HHL‑5 cells with steatosis, and downregulated the expression levels of pro‑survival proteins, such as Bcl‑2, p‑Akt and p‑Erk1/2, whereas the expression levels of pro‑apoptotic Bax were markedly increased. In conclusion, although there are some reports regarding the protective effect of Rg1 on fatty liver cells, to the best of our knowledge, the present study is the first to report that Rg1 may exert an anti‑apoptotic effect on fatty liver cells by regulating SGPL1 in the sphingosine signaling pathway. Rg1 is the main component of the prescription drug Xuesaitong in China; therefore, the findings of the present study may provide a theoretical molecular basis for the use of Rg1 or Xuesaitong in the treatment of patients with NAFLD.

Non‑alcoholic fatty liver disease (NAFLD) is a widespread threat to human health. However, the present screening methods for NAFLD are time‑consuming or invasive. The present study aimed to assess the potential of microRNAs (miRNAs/miRs) in serum extracellular vesicles (EVs) as a biomarker of NAFLD. C57BL/6J mice were fed either a 12‑week high‑fat diet (HFD) or standard chow to establish NAFLD and control groups, respectively. Serum samples were obtained from the mouse model of NAFLD, as well as 50 patients with NAFLD and 50 healthy individuals, and EVs were extracted and verified. Using reverse transcription‑quantitative PCR, the mRNA expression level of selected miRNAs in the serum and EVs was analyzed. In order to determine the diagnostic value, receiver operating characteristic (ROC) curves were used. The mice treated with HFD showed notable hepatic steatosis and higher concentrations of serum alanine aminotransferase (ALT). There was also a significant decrease in the expression levels of miR‑135a‑3p, miR‑129b‑5p and miR‑504‑3p, and an increase in miR‑122‑5p expression levels in circulating EVs in mice treated with HFD and patients with NAFLD. There were also similar miR‑135a‑3p and miR‑122‑5p expression patterns in the serum. ROC analysis demonstrated that miR‑135a‑3p in circulating EVs was highly accurate in diagnosing NAFLD, with the area under the curve value being 0.849 (95% CI, 0.777‑0.921; P<0.0001). Bioinformatics analysis indicated that dysregulated miR‑135a‑3p was associated with \'platelet‑derived growth factor receptor signaling pathway\' and \'AMP‑activated protein kinase signaling pathway\'. In summary, circulating miR‑135a‑3p in EVs may serve as a potential non‑invasive biomarker to diagnose NAFLD. This miRNA was a more sensitive and specific biological marker for NAFLD compared with ALT.

Nowadays, metabolic syndromes are emerging as global epidemics, whose incidence are increasing annually. However, the efficacy of therapy does not increase proportionately with the increased morbidity. Type 2 diabetes mellitus (T2DM) and non‑alcoholic fatty liver disease (NAFLD) are two common metabolic syndromes that are closely associated. The pathogenic mechanisms of T2DM and NAFLD have been studied, and it was revealed that insulin resistance, hyperglycemia, hepatic lipid accumulation and inflammation markedly contribute to the development of these two diseases. The 2‑series prostaglandins (PGs), a subgroup of eicosanoids, including PGD2, PGE2, PGF2α and PGI2, are converted from arachidonic acid catalyzed by the rate‑limiting enzymes cyclooxygenases (COXs). Considering their wide distribution in almost every tissue, 2‑series PG pathways exert complex and interlinked effects in mediating pancreatic β‑cell function and proliferation, insulin sensitivity, fat accumulation and lipolysis, as well as inflammatory processes. Previous studies have revealed that metabolic disturbances, such as hyperglycemia and hyperlipidemia, can be improved by treatment with COX inhibitors. At present, an accumulating number of studies have focused on the roles of 2‑series PGs and their metabolites in the pathogenesis of metabolic syndromes, particularly T2DM and NAFLD. In the present review, the role of 2‑series PGs in the highly intertwined pathogenic mechanisms of T2DM and NAFLD was discussed, and important therapeutic strategies based on targeting 2‑series PG pathways in T2DM and NAFLD treatment were provided.