4,4-Dimethylsterols Reduces Fat Accumulation via Inhibiting Fatty Acid Amide Hydrolase In Vitro and In Vivo.

4,4-Dimethylsterols constitute a unique class of phytosterols responsible for regulating endogenous cannabinoid system (ECS) functions. However, precise mechanism through which 4,4-dimethylsterols affect fat metabolism and the linkage to the ECS remain unresolved. In this study, we identified that 4,4-dimethylsterols, distinct from 4-demethseterols, act as inhibitors of fatty acid amide hydrolases (FAAHs) both in vivo and in vitro. Genetic ablation of FAAHs (faah-1) abolishes the effects of 4,4-dimethylsterols on fat accumulation and locomotion behavior in a Caenorhabditis elegans model. We confirmed that dietary intervention with 4,4-dimethylsterols in a high-fat diet (HFD) mouse model leads to a significant reduction in body weight (>11.28%) with improved lipid profiles in the liver and adipose tissues and increased fecal triacylglycerol excretion. Untargeted and targeted metabolomics further verified that 4,4-dimethylsterols influence unsaturated fatty acid biosynthesis and elevate oleoyl ethanolamine levels in the intestine. We propose a potential molecular mechanism in which 4,4-dimethylsterols engage in binding interactions with the catalytic pocket (Ser241) of FAAH-1 protein due to the shielded polarity, arising from the presence of 2 additional methyl groups (CH3). Consequently, 4,4-dimethylsterols represent an unexplored class of beneficial phytosterols that coordinate with FAAH-1 activity to reduce fat accumulation, which offers new insight into intervention strategies for treating diet-induced obesity.

The Effect of Whey Protein Isolate Hydrolysate on Digestive Properties of Phytosterol.

Phytosterol (PS) is a steroid, and its bioavailability can be enhanced by interacting with protein in the C-24 hydroxyl group. The interaction between sterols and amino acid residues in proteins can be enhanced by enzymatic hydrolysis. Phytosterol and whey insulation hydrolysates (WPH1-4) fabricated by the Alcalase enzyme at different enzymatic hydrolysis times were selected as delivery systems to simulate sterol C-24 hydroxyl group interaction with protein. Increasing hydrolysis time can promote the production of ß-Lg, which raises the ratio of ß-turn in the secondary structure and promotes the formation of interaction between WPH and PS. The correlation coefficient between hydrogen bonds and encapsulation efficiency (EE) and bioaccessibility is 0.91 and 0.88 (P < 0.05), respectively, indicating that hydrogen bonds of two components significantly influenced the combination by concealing the hydrophobic amino acids and some residues, which improved PS EE and bioavailability by 3.03 and 2.84 times after PS was combined with the WPI hydrolysate. These findings are expected to enhance the absorption of PS and other macromolecules by protein enzymatic hydrolysis to broaden their applications for food.

Acer truncatum Bunge seed oil ameliorated oxaliplatin-induced demyelination by improving mitochondrial dysfunction via the Pink1/Parkin mitophagy pathway.

Dietary nutritional support for special populations is an effective and feasible method to improve the quality of life of patients and reduce medical pressure. Acer truncatum Bunge seed oil (ATSO) is widely recognized for its ability to promote nerve myelin regeneration. To evaluate the ameliorative effects of ATSO on chemotherapy-induced demyelination, a zebrafish model of chemotherapy-induced demyelination was established. The results showed that 100 µg mL-1 of ATSO reversed tail morphology damage, axon degeneration, touch response delay, ROS level upregulation and the expression of myelin basic protein decrease in chemotherapy-induced zebrafish. In addition, the expression of myelin markers (including sox10, krox20, and pmp22) in oxaliplatin-induced cells was markedly reversed by ATSO and its active components (gondoic acid, erucic acid, and nervonic acid). ATSO and its active components could reverse demyelination by ameliorating mitochondrial dysfunction. Conversely, linoleic acid and linolenic acid promoted demyelination by exacerbating mitochondrial dysfunction. Moreover, the Pink1/Parkin pathway was recognized as the main reason for ATSO and its active components improving mitochondrial function by activating mitophagy and restoring autophagic flow. Taken together, this study demonstrated that ATSO and its active components could be further developed as novel functional food ingredients to antagonize demyelination.

Interactions between dietary cholesterol and intestinal flora and their effects on host health.

The interactions between dietary cholesterol and intestinal microbiota strongly affect host health. In recent years, relevant studies have greatly advanced this field and need to be summarized to deepen the understanding of dietary cholesterol-intestinal microbiota interactions and their effects on host health. This review covers the most recent frontiers on the effects of dietary cholesterol on the intestinal microbiota and its metabolites, the metabolism of cholesterol by the intestinal microbiota, and the effects of the interactions on host health. Several animal-feeding studies reported that dietary cholesterol altered different intestinal microbiota in the body, while mainly causing alterations in intestinal microbial metabolites such as bile acids, short-chain fatty acids, and tryptophan derivatives. Alterations in these metabolites may be a novel mechanism mediating cholesterol-related diseases. The cholesterol microbial metabolite, coprostanol, has a low absorption rate and is excreted in the feces. Thus, microbial conversion of cholesterol-to-coprostanol may be an important way of cholesterol-lowering by the organism. Cholesterol-3-sulfate is a recently discovered microbial metabolite of cholesterol, mainly metabolized by Bacteroides containing the Bt_0416 gene. Its effects on host health have been preliminarily characterized and are mainly related to immune modulation and repair of the intestinal epithelium.

Application of small angle X-ray scattering in exploring the effect of edible oils with different unsaturation FAs on bioaccessibility of stigmasterol oleate.

BACKGROUND: Phytosterol can improve its lipid solubility, lipophilic/hydrophilic balance and bioaccessibility by esterification with fatty acids, which increases its practical application range in the food industry. In the present study, small angle X-ray scattering combined with the pH-stat in vitro digestion model was applied to continuously monitor the molecular structure evolution of mixed micelles during digestion and investigate the effect of three edible oils (olive oil with 72.41 ± 0.57% oleic, sunflower seed oil with 63.45 ± 0.78% linoleic, refined linseed oil with 51.74 ± 0.34% linolenic) on bioaccessibility of stigmasterol oleate in vitro. RESULTS: The release degree and rate of fatty acids in the three edible oil systems (kOO+ST-OA = 0.0501, kSO+ ST-OA = 0.0357, kLO+ST-OA = 0.0323) was compared. The three different edible oils had similar impact on the formation of dietary mixed micelles during the simulatedin vitro digestion of stigmasterol oleate, although there were significant differences in molecular morphology and composition of mixed micelles. The results showed that the vesicles formed by linoleic oil (SO system) or linolenic oil (LO system) were easy to dissociate. The largest average number and diameter of vesicles (5.55 × 1016 cm-3 and 2230.75 Å), the most stable vesicle structure and the fastest fatty acid release rate were observed in the OO system. CONCLUSION: Compared to linoleic (SO system) or linolenic (LO system), the oleic (OO system) could facilitate the transformation of micelles to vesicles and maintain the stability of its membrane, significantly promotin the dissolution of stigmasterol and improving bioaccessibility. © 2023 Society of Chemical Industry.

Single-Cell Transcriptomics Reveals the Difference of Aortic Atherosclerosis Response to Phytosterols and Oxidation Products of Sterols.

SCOPE: Phytosterols (PS) and sterol oxidation products are key dietary factors influencing atherosclerosis besides cholesterol, although the mechanisms remain elusive. Recently, single-cell RNA sequencing (scRNA-seq) has revealed the heterogeneity of multiple cell types associated with complex pathogenesis in atherosclerosis development. METHODS AND RESULTS: Here, scRNA-seq is performed to investigate the alterations in the aortic cells from ApoE-/- mice induced by diet-derived PS or two sterol oxidation products, phytosterols oxidation products (POPs), and cholesterol oxidation products (COPs). The study identifies four fibroblast subpopulations with different functions, and immunofluorescence demonstrates their spatial heterogeneity, providing evidence that suggests the transformation of smooth muscle cells (SMCs) and fibroblasts in atherosclerosis. The composition and gene expression profiles of aortic cells change broadly in response to PS/COPs/POPs exposure. Notably, PS exhibits an atheroprotective effect where different gene expressions are mainly found in B cells. Exposure to COPs accelerates atherosclerosis and results in marked alternations in myofibroblast subpopulations and T cells, while POPs only alter fibroblast subpopulations and B cells. CONCLUSION: The data elucidate the effects of dietary PS/COPs/POPs on aortic cells during atherosclerosis development, especially on the newly identified fibroblast subpopulations.

Protective Effect of Orbitides from Linseed (Linum usitatissimum L.) against Ultraviolet B-induced Photoaging in Zebrafish.

Excessive ultraviolet (UV) exposure is the primary environmental factor that contributes to skin aging. Orbitides have been considered as important functional components in linseed, and they are complex and multiple. In this study, linseed orbitides (LOs) were divided into oxidized linseed orbitides (OLOs) and reduced linseed orbitides (RLOs) and used to investigate protection against ultraviolet B-induced photoaging in zebrafish. First, the results of the zebrafish embryo acute toxicity test showed that the OLOs had obvious embryo toxicity compared with RLOs. And RLOs had better effect in ultraviolet B-treated zebrafish, which may significantly reduce the reactive oxygen species levels and inhibit the degradation of collagen. Besides, we also found that RLOs could effectively inhibit the oxidation of proteins and lipids and regulate the activity of antioxidant enzymes. Furthermore, neutrophil recruitment to the dorsal and caudal fin regions was observed in UVB-treated zebrafish, and RLOs effectively alleviated this migration. In conclusion, RLOs have strong photoprotective effects and potential to be used as antiphotoaging ingredients.

Advances on Cyclocarya paliurus polyphenols: Extraction, structures, bioactivities and future perspectives.

Cyclocaryapaliurus (C. paliurus) is an edible and medicinal plant, distributed in southern China. As a kind of new food raw material, the leaves of C. paliurus are processed as tea products in daily life. C. paliurus is recognized as a good source to polyphenols, showing excellent bioactivities, which has attracted more and more attention. Polyphenols are important functional bioactive components in C. paliurus. C. paliurus polyphenols perform nutritional functions in anti-diabetes, anti-hyperlipidemic, anti-obesity, anti-oxidant, and other activities. In this review, we summarize the research progress of extraction technologies, structural characteristics, and bioactivities of C. paliurus polyphenols. Other potential functions of C. paliurus polyphenols are prospected. This review provides a reference for further research and applications of C. paliurus polyphenols in a field of functional food and medicines.

The relationship between flavor formation, lipid metabolism, and microorganisms in fermented fish products.

Traditional fermented fish products are favored due to their unique flavors. The fermentation process of fish is accompanied by the formation of flavor substances through a complex metabolic reaction of microorganisms, especially lipolysis and lipid oxidation. However, it is difficult to precisely control the reaction of microorganisms during the fermentation process in modern industrial production, and fermented fish products have lost their traditional characteristic flavors. The purpose of this review is to summarize the different kinds of fermented fish, core microorganisms in it, and flavor formation mechanisms, providing guidance for industrial cultural starters. Future research on the flavor formation mechanism is necessary to confirm the relationship between flavor formation, lipid metabolism, and microorganisms to ensure stable flavor and safety, and to elucidate the mechanism directly toward industrial application.

Characterization of fatty acids, triacylglycerols, phytosterols and tocopherols in peony seed oil from five different major areas in China.

Peony (Paeonia lactiflora pall) is a unique plant in China, which is planted on a large scale in different areas. The study characterized the triacylglycerol (TAG), fatty acid (FA), phytosterol, and tocopherol in peony seed oil (PSO) from five cultivation areas in China. The FAs in PSO were mainly C18 fatty acyl chains, especially α-linolenic acid (C18:3n-3). The triacylglycerol of PSO was identified by UPLC-Q-ToF/MS, and the predominant TAGs were LnLnLn, LLnLn, LLLn, LnLO/LLL, and OOLn/OLL. As for the micronutrients, γ-tocopherol and ß-sitosterol were main components of tocopherol and phytosterol, respectively. The obtained data were further analyzed by principal components analysis (PCA), which allowed differentiation of five PSOs by their cultivation areas. For the great potential in unsaturated fatty acid and micronutrients, PSO could be a good dietary resource of plant oil.