Gastrointestinal (GI) tumors, characterized by high incidence and mortality rates, represent a major global health challenge. Metabolic reprogramming has been recognized as one of their defining hallmarks. Beyond aberrant glucose metabolism, accumulating evidence has revealed how dysregulated fatty acid (FA) metabolism plays a multifaceted role in regulating the tumor microenvironment (TME). By modulating tumor, immune, and stromal cells, FA metabolism profoundly influences tumorigenesis, progression, and cell death. Despite advances in current treatments, the inherent immunosuppressive nature of TME and the therapeutic resistance of tumor cells still remain major obstacles. Notably, targeting key nodes of FA metabolism has emerged as a promising strategy to overcome these challenges. Thus, in this review, we systematically delineate how FA metabolic reprogramming shapes the GI tumor microenvironment by regulating tumor, immune, and stromal cells in multiple ways. Furthermore, we critically explore the translational potential of FA metabolism in biomarker development, targeted therapy, and combination therapeutic strategies. By synthesizing these insights, this review aims to provide forward-looking perspectives on future therapeutic strategies against GI tumors.

An emerging body of evidence has highlighted the complex interplay among obesity, insulin resistance, and the gut microbiota. This observational study aimed to evaluate differences in intestinal microbiome profiles between individuals with obesity, with and without insulin resistance. Twenty individuals with obesity aged 20-50 years were enrolled and categorized according to insulin resistance status (N = 10 per group), as determined using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Fasting blood samples were collected and analyzed for glucose, lipid profiles, insulin, free fatty acids, and high-sensitivity C-reactive protein (hsCRP). Fecal DNA was extracted, and its quantity and quality were assessed.The V3-V4 region of 16s rRNA was amplified using specific primers, purified, and sequenced on the MiSeq Illumina platform with paired-end reads. The two groups showed notable disparities in fasting glucose (p=0.002), insulin (p<0.001), and HOMA-IR indices (p<0.001). While Alpha diversity remained comparable between groups when assessed using Shannon’s and Simpson’s indexes (but was significant for the Chao1 index), beta diversity was lower in the insulin-resistant group (p<0.05). Short-chain fatty acid-producing bacteria such as members of Lachnospiraceae family, Oscillospirales , and Faecalibacterium prausnitzii , were significantly enriched in insulin-sensitive individuals. In contrast, Alistipes putredenis was more abundant in those with insulin resistance. KEGG Orthology (KO) analysis revealed distinct functional enrichment: the Insulin Resistance group was enriched in carbohydrate metabolism pathways (e.g., glycolysis/gluconeogenesis, TCA cycle), while the Insulin Sensitive group showed more diverse metabolic activity, including amino acid and fatty acid metabolism, butyrate metabolism, and select carbohydrate pathways. These findings contribute to understanding the role of gut microbiota in metabolic heterogeneity associated with insulin resistance in obesity. • Beta diversity was significantly different between the groups, being lower in the Insulin- Resistance (IR) group, which indicates a distinct microbial community structure. • The study found two dominant enterotypes: the Prevotella genus and the Bacteroides genus. • The Insulin-Sensitive (IS) group was enriched in beneficial, short-chain fatty acid-producing bacteria, specifically members of the Lachnospiraceae family and species such as Faecalibacterium prausnitzii. • The Insulin-Resistant (IR) group had a higher abundance of proinflammatory bacteria, including Alistipes putredinis (also called Alistipes obesi ) and Escherichia–Shigella. • Predicted Functions: The microbiota in the IR group was enriched in carbohydrate metabolism pathways, whereas the IS group's microbiota showed greater activity in amino acid, fatty acid, and butyrate metabolism.

BPA impairs the intestinal health of Gobiocypris rarus by disrupting gut microbiota, altering fatty acid metabolism, and affecting mucus secretion.

Downregulated ECHS1 and HADH-mediated fatty acid β-oxidation contributes to mitochondrial dysfunction in salivary glands of Sjögren's syndrome.

Dietary myo-inositol exerts pleiotropic effects on T cell activation, antioxidant defense and fatty acid metabolism to enhance anti-bacterial immunity in tilapia.

ACSL6 alleviates myocardial hypertrophy by ameliorating cardiac lipid synthesis and mitochondrial function.

The gut microbiota is a key regulator of host metabolism and skeletal muscle physiology, yet its role in muscle fiber-type transformation in pigs remains unclear. Here, we used germ-free (GF) and specific pathogen-free (SPF) Rongcheng piglets to explore how microbial absence influences muscle development. GF piglets showed significantly reduced body weight and an increased proportion of fast-twitch fibers compared with SPF controls. Transcriptome sequencing identified 1332 differentially expressed genes (DEGs), notably those involved in cGMP-PKG, Thyroid hormone, HIF-1, VEGF, and Butanoate metabolism signaling pathways, which are essential for myofiber specification. Non-targeted metabolomic profiling revealed 320 differentially expressed metabolites (DEMs), with major alterations in Bile secretion. Integrated transcriptomic and metabolomic uncovered 10 KEGG pathways co-enriched with DEGs and metabolites, including Bile secretion, Ferroptosis, Inflammatory mediator regulation of TRP channels, and HIF-1 signaling pathway. Correlation analysis revealed that strong positive correlations were observed between fast-twitch fiber genes (e.g., PRKCA, MYOZ3, NFATC1) and fatty acid-related metabolites (e.g., Dodecanoic acid, Valproic Acid, and Decanoic acid), whereas negative correlations were detected between these genes and bile acid-related metabolites (e.g., Cholic acid and 7-Ketolithocholic acid), suggesting microbial metabolites is associated with muscle fiber phenotype via metabolic and signaling crosstalk. Collectively, our findings demonstrate that gut microbial absence in pigs disrupts bile acid metabolism and fatty acid metabolism, which in turn drives the shift of skeletal muscle fiber composition toward fast-twitch glycolytic fibers. These metabolites are identified as key microbial mediators linking the gut microbiota to the transcriptional regulatory function of porcine muscle fiber type specialization, providing new insights into the gut-muscle axis and highlighting the important role of microbiota-derived metabolites in maintaining porcine muscle fiber composition and metabolic balance.

The Warburg effect refers to a metabolic reprogramming process characterized by enhanced glycolysis and lactate production, even in the presence of adequate oxygen. This phenomenon is a critical adaptation enabling tumor cells to satisfy their elevated energy and biosynthetic requirements. This review synthesizes key regulators within the glycolytic signaling pathways and examines the dynamic interplay between glycolysis and other metabolic processes, including oxidative phosphorylation (OXPHOS) and fatty acid metabolism. Special emphasis is placed on how intravital imaging provides real-time insights into these metabolic alterations. Furthermore, this review underscores the central role of glycolysis in the tumor metabolic network and its contribution to resistance mechanisms against chemotherapy and radiotherapy. Finally, it discusses the latest developments in targeted therapies, reviewing the clinical progress of glycolysis inhibitors (e.g., curcumin, docetaxel) and exploring future directions for combining metabolic interventions with immunotherapy and other innovative approaches. These insights promise to offer novel perspectives on tumor metabolic reprogramming and the evolution of precision therapies.

PDAP1 reprograms fatty acid metabolism and drives malignant transformation via HSPA8-Mediated ERK/MAPK activation in hepatocellular carcinoma.

Unveiling the roles of oxidative stress defense and energy metabolism adjustment in low-temperature stress responses of Apostichopus japonicus: An integrated physiological, transcriptomic and metabolomic analysis.

PRMT1 and its Substrates: Novel functions in kidney and metabolic diseases.

Influence of light irradiance on the toxicity of graphitic carbon nitride to algae: Intensified nano-bio interactions driven by particle reassembly.

Multi-omics dissection of large-size formation in Eriocheir sinensis: Insights from RNA, metabolite profiling, and ceRNA regulatory networks.

Double burden: microfilariae infection amplifies metabolic costs of moult in breeding male village weavers (Ploceus cucullatus).

Effect of packaging-induced oxygen microenvironments on the viability and metabolism of Lactobacillus paracasei in yogurt.

Sublethal deltamethrin exposure dysregulates brain fatty acid homeostasis in honey bee (Apis mellifera).

OXCT1-induced succinylation at K81 shields HADH from HSPA8-Mediated degradation in alveolar epithelial cells to attenuate lung ischemia-reperfusion injury.

Myocardial ischemia-reperfusion injury (MIRI) is a major clinical challenge, marked by metabolic disruptions and cellular damage following the restoration of blood flow after ischemia. During ischemia, the heart shifts from fatty acid metabolism to glucose metabolism, leading to metabolic abnormalities, including reduced intracellular pH, ion disturbances, cell swelling, and apoptosis. Upon reperfusion, fatty acid β-oxidation resumes, becoming the dominant energy source, which induces excessive oxidative stress and aggravates myocardial injury. To explore the role of FTO (Fat mass and obesity-associated protein) in m6A demethylation of MZF1 and its regulation of DECR1, a key enzyme involved in fatty acid β-oxidation, in the context of MIRI. We investigated the molecular mechanisms by which FTO-mediated m6A modification of MZF1 regulates DECR1 expression, leading to enhanced fatty acid oxidation during reperfusion and its contribution to the exacerbation of MIRI. Our findings suggest that FTO-mediated demethylation of MZF1 promotes the expression of DECR1, thereby enhancing fatty acid oxidation. This process intensifies oxidative stress and worsens myocardial injury during ischemia/reperfusion. The FTO-mediated m6A modification of MZF1 represents a critical mechanism in the regulation of fatty acid oxidation and the exacerbation of MIRI. These insights offer potential therapeutic targets to mitigate the harmful effects of reperfusion injury in myocardial infarction.

Multi-omics reveal the mechanism of Plantaricin BM-1 in controlling yoghurt post-acidification by affecting the membrane and metabolism of Lactobacillus delbrueckii subsp. bulgaricus.

Spatial metabolomics reveals the therapeutic mechanisms of Shengjiang Xiexin decoction in modulating gut-liver axis fatty acid metabolism for the treatment of Clostridioides difficile infection.