Whether different forms of n-3 polyunsaturated fatty acids (PUFA) have differential functions to improve cardiac damage remain elusive. The present study aimed to investigate different forms of n-3 PUFA intervention, namely eicosapentaenoic acid (C_{20:5 n-3}, EPA)/docosahexaenoic acid (C_{22:6 n-3}, DHA)-triglyceride (TAG), DHA/EPA-phospholipid (PL), and krill oil on high-fat/high-cholesterol diet (HFD)-induced myocardial injury. After 18 weeks of HFD feeding, the mice exhibited myocardial hypertrophy and disordered arrangement of cardiomyocytes. However, administration of the 3 forms of n-3 PUFA significantly led to alleviated myocardial hypertrophy and arrangement of myocardial cells in the C57BL/6J mice under HFD challenge. Meanwhile, administration of the 3 forms of n-3 PUFA ameliorated myocardial hypertrophy in low-density lipoprotein receptor knockout (LDLR^–/–) mice. However, n-3 PUFA intervention ameliorated HFD-induced cardiac dysfunction by increasing ejection fraction and fraction shortening levels, no significant difference was observed with respect to cardiac dysfunction between the 3 forms of n-3 PUFA groups. The lipidomics and targeted lipidomics analyses identified and confirmed that cardiac C_18:0-, C_20:0-, C_22:0-, and total ceramide concentrations in EPA/DHA-TAG and DHA/EPA-PL groups were significantly lower in comparison with the HFD group. Mechanistically, n-3 PUFA treatment significantly increased the protein expression levels of adiponectin and acid ceramidase, which accelerate ceramide catabolism. The reduced cardiac ceramide concentrations were associated with remodeling mitochondrial dynamics homeostasis and decreased dynamin-related protein 1 (Drp1) and mitochondrial fission factor (MFF) levels. Consequently, the protein expression levels of caspase 3 and recombinant tumor protein p53 (p53) were significantly decreased in the three n-3 PUFA groups compared with the HFD group. This work reveals that n-3 PUFA mitigate cardiac dysfunction through the adiponectin/ceramide/apoptosis axis, but there is no significant difference between the 3 forms of n-3 PUFA groups.

The synergistic antihyperglycemic effects of wheat bran insoluble dietary fiber (WBIDF) complexed with inulin (IN) were investigated in this study. In vitro fecal fermentation demonstrated that WBIDF-IN significantly increased the production of short-chain fatty acids (SCFAs), particularly acetic and butyric acids, outperforming WBIDF and other WBIDF-soluble dietary fiber (SDF) complexes (including WBIDF-stachyose, WBIDF-fructo-oligosaccharides, and WBIDF-resistant dextrin). Subsequently, db/db mice received the optimized complex for 12 weeks. Compared with WBIDF or IN alone, WBIDF-IN supplementation significantly lowered fasting blood glucose, improved glucose tolerance, enhanced insulin sensitivity by reducing fasting insulin and HOMA-IR, and promoted GLP-1 secretion. HE staining revealed that WBIDF-IN markedly preserved islet morphology and cellular integrity, while immunofluorescence analysis confirmed the restoration of insulin expression to near-normal levels. 16S rRNA sequencing revealed that WBIDF-IN improved gut microbial diversity and shifted the microbial composition by enriching SCFAs-producing genera such as Muribaculaceae, Ruminococcaceae, and Alloprevotella, while reducing harmful taxa like Romboutsia and Enterococcus. Correlation analysis further revealed that the relative abundance of Alloprevotella was positively associated with colonic SCFAs and GLP-1 levels, but negatively correlated with fasting blood glucose. Collectively, these findings demonstrated that WBIDF-IN complexation exerts enhanced antihyperglycemic effects primarily through microbiota-mediated SCFAs production, which promoted GLP-1 secretion and pancreatic islet protection, providing a promising dietary strategy for type 2 diabetes management.

Phytosterols are widely recognized bioactive compounds exhibiting anti-inflammatory effects. Macrophages adopt a distinct lipid metabolic state during inflammatory responses. However, the specific mechanisms by which phytosterols influence macrophage lipid metabolism and subsequently regulate inflammation through metabolic remodeling remain unclear. In this study, we elucidate how phytosterols reprogram macrophage lipid metabolism to attenuate inflammatory responses. Quantitative lipidomic analysis revealed that phytosterol-induced lipid remodeling predominantly affects long-chain triglycerides. Further mechanistic studies demonstrated that phytosterols increase lipid droplet accumulation and regulate their metabolism by suppressing adipose triglyceride lipase (ATGL), upregulating hypoxia inducible lipid droplet associated proteins (HILPDA), and reducing the production of pro-inflammatory intermediates, including arachidonic acid. Consequently, phytosterol treatment decreased prostaglandin E₂ (PGE₂) levels and reduced the secretion of pro-inflammatory cytokines such as IL-1β. Collectively, these findings provide novel mechanistic insights into how phytosterols reduce macrophage-driven inflammation through lipid metabolic reprogramming.

With the aging of the population and the concomitant increase in obesity rates, the medical and socioeconomic impacts of osteoporosis are expanding rapidly. Medium-chain triglycerides (MCT) and high-oleic peanut oil (HOP) are dietary fats with evidenced metabolic benefits, including weight management and regulation of glucose-lipid homeostasis metabolism. However, the differences in efficacy and underlying mechanisms between MCT and HOP in osteoporosis are still unclear. In this study, the osteoporosis mice induced by high-fat diet were treated with MCT and HOP for nine weeks. The results showed that both MCT and HOP reduced body weight, elevated bone mineral density and bone biomechanical quality, and improved the adverse changes of stroma and trabecular in the bone marrow to some extent, in which HOP exhibited more effective effects. Mechanistically, HOP treatment activated the PI3K/AKT and ERK signaling pathways and upregulated Runx2 expression, thereby promoting osteogenic differentiation of bone mesenchymal stem cells. In summary, HOP exhibited superior efficacy in improving osteoporosis induced by obesity compared to MCT, whereas MCT was more conducive to weight loss without compromising bone health. These results provide new evidence for the use of HOP and MCT in patients with osteoporosis.