Search Results (559)

Background: The metabolic dysfunction-associated steatotic liver disease (MASLD) represents an escalating global health concern, with effective treatments still lacking. Given its complex pathogenesis, multi-targeted strategies are highly desirable. Methods: This study reports the isolation of four flavone C-glycosides (FCGs) from Dianthus superbus L. and explores their potential in treating MASLD. The bioactivity and underlying mechanisms of FCGs were systematically evaluated by integrating network pharmacology, molecular docking, and zebrafish model validation. Results: Network pharmacology analysis revealed that FCGs may modulate multiple MASLD-related pathways, including lipid metabolism, insulin signaling, inflammation, and apoptosis. Molecular docking further confirmed strong binding affinities between FCGs and key protein targets involved in these pathways. In the zebrafish model of MASLD induced by egg yolk powder, FCGs administration markedly attenuated obesity, hepatic lipid accumulation, and liver tissue damage. Furthermore, FCGs improved lipid metabolism and restored locomotor function. Molecular analyses confirmed that FCGs upregulated PPARγ expression to promote lipid metabolism, restored insulin signaling by enhancing INSR, PI3K, and AKT expression, and suppressed inflammation by downregulating TNF, IL-6 and NF-κB. Additionally, FCGs inhibited hepatocyte apoptosis by elevating the BCL-2/BAX ratio. Conclusions: These findings highlight the multi-pathway regulatory effects of FCGs in MASLD, underscoring its potential as a novel therapeutic candidate for further preclinical development. Full article

Background/Objectives: Diatomaceous earth (DE), a natural substance rich in amorphous silica and recognized as a food additive, is gaining attention as a dietary silicon supplement. However, its bioavailability and impact on lipid digestion and absorption remain poorly characterized. This study aimed to investigate silicon bioavailability after short-term DE supplementation and its effects on postprandial glycemia and triglyceridemia, the expression of lipid metabolism-related proteins, and the modulation of the intestinal mucosal barrier. Methods: Female Wistar rats received daily oral supplementation of DE (equivalent to 2 or 4 mg silicon/kg body weight) for one week. Silicon digestibility, excretion, and hepatic accumulation were quantified. Postprandial glycemia and triglyceridemia were monitored. Lipid profile was analyzed by HPSEC in gastric and intestinal contents. Jejunal morphology and mucin-secreting cells were assessed histologically. Lipid metabolism markers were evaluated by immunohistochemistry and Western blot in both intestinal and hepatic tissues. Results: DE supplementation enhanced silicon absorption and increased hepatic levels. Fecal output and moisture content were also elevated, especially at the higher dose. DE significantly reduced postprandial triglyceridemia and consequently increased luminal triglyceride retention. These changes were associated with decreased jejunal levels of IFABP, ACAT2, and MTP, as well as reduced hepatic levels of MTP and LDLr, alongside increased levels of ABCG5/G8 and LXRα/β, indicating a partial blockage of lipid absorption and enhanced cholesterol efflux. The effects on the intestinal barrier were evidenced by villi shortening and an increase in mucin-producing cells. Conclusion: Food-grade DE is a bioavailable source of silicon with hypolipidemic potential, mainly by reducing intestinal lipid absorption. This is supported by lower postprandial triglycerides, increased luminal lipid retention, and decreased expression of lipid transport proteins. The study in healthy female rats underscores the importance of sex-specific responses and supports DE as a dietary strategy to improve lipid metabolism. Full article

Background/Objectives: Asprosin is the endogenous ligand of the olfactory Olfr734 receptor linked to MASLD and glucose metabolism. Despite the involvement of asprosin in these processes, little has been published on the specific role of Olfr734 in liver function. The aim of this work is therefore to study the specific role of the olfactory Olfr734 receptor in MASLD and glucose metabolism. Methods: To achieve this objective, we performed a genetic inhibition specifically to inhibit Olfr734 in the livers of male mice. We then studied the progression of MASLD in DIO mice. In addition, we studied the glucose metabolism in hypoglycemia states and postprandial glucose production in standard diet-fed mice. Finally, analyses of liver biopsies from patients with obesity and with or without T2DM were conducted. Results: We found that hepatic Olfr734 levels vary according to changes in nutritional status and its knockdown effect in the liver is to increase the hepatic lipid content in DIO mice. Our results also showed that OLFR734 expression is involved in the adaptive response in terms of glucose production to nutrient availability. Finally, the hepatic human Olfr734 ortholog named OR4M1 has been observed to be at significantly higher levels in male patients with T2DM. Conclusions: This study increases understanding of the mechanisms by which the modulation of Olfr734 expression affects liver function. Full article

Background/Objectives: As an essential polyunsaturated fatty acid, linoleic acid (LA) plays an important role in maintaining the integrity of cellular membranes, modulating inflammatory responses, and mediating intracellular signaling. This review explores the structure, properties, and nutritional significance of LA and its bioactive derivatives, with particular attention to sustainable production methods and their potential applications. Methods: A comprehensive review of the recent literature was conducted, emphasizing the use of green synthesis techniques, such as enzyme-catalyzed biocatalysis and microbiological transformations, in order to obtain LA-derived nutraceuticals. Analyses were conducted on the key aspects related to food industry applications, regulatory frameworks, and emerging market trends. Results: Through green synthesis strategies, LA derivatives with antioxidant, anti-inflammatory, and antimicrobial properties have been developed. There is potential for these compounds to be incorporated into health-oriented food products. In spite of this, challenges remain regarding their stability and bioavailability. Furthermore, there are inconsistencies in international regulatory standards which prevent these compounds from being widely adopted. Conclusions: The development of functional and sustainable food products based on linoleic acid derivatives obtained using ecological methods offers significant potential. Research is required to optimize production processes, enhance compound stability, and clinically validate health effects. The integration of the market and the safety of consumers will be supported by addressing regulatory harmonization. Full article

Background: Oligopeptides from sea cucumber eggs (SCEPs) are rarely studied for their neuroprotective effects. Methods: Therefore, we prepared SCEPs via simulated gastrointestinal digestion and then administered them to an Alzheimer’s disease (AD) mouse model via gavage. Behavior tests, gut–brain histopathology and fecal microbiota transplantation (FMT) experiments were conducted, and gut microbiota and metabolite short-chain fatty acids (SCFAs) were evaluated via 16sRNA gene sequencing and LC-MS. Results: The results showed that both the SCEP and FMT groups experienced improvements in the cognitive impairments of AD and showed reduced levels of Aβ, P-Tau, GFAP, and NFL in the brain, especially in the hippocampus. SCEP remodeled the gut microbiota, increasing the relative abundances of Turicibacter and Lactobacillus by 2.7- and 4.8-fold compared with the model at the genus level. In the SCEP and FMT treatments, four SCFA-producing bacteria obtained from gut microbiota profiling showed consistent trends, indicating that they may be involved in mediating the neuroprotective effects of SCEP. Mechanically, SCEP regulated the SCFA distribution in feces, blood, and the brain, greatly increased the content of SCFAs in the brain up to 2000 μg/mg, eased gut–brain barrier dysfunction, inhibited HDAC3 overexpression, and upregulated BDNF/NT3 levels. Conclusions: This study provides a promising candidate for preventing AD and a reference for applying SCEP. Full article

Background/Objectives: Studies demonstrate better health outcomes for infants consuming milk with higher concentrations of ω3 (ALA and DHA) and negative health outcomes associated with higher ω6 (LA and AA) PUFAs. We studied the relationship between maternal BMI and PUFA levels in maternal plasma and breast milk. Methods: Women at 7–8 weeks postpartum were grouped according to normal BMI (18–24.9 kg/m²) and overweight/obese (OW/OB; ≥25 kg/m²). Maternal blood and continuous breast milk samples obtained from foremilk to hindmilk were analyzed for lipidomics. Results: The plasma levels of ω3 and ω6 PUFA were significantly lower in OW/OB subjects, with a total ω3 and ω6 FA level of 50% for women with normal BMI. Conversely, breastmilk levels of total ω3 and ω6, including their respective precursors of LCFAs (ALA and LA), were significantly increased in both foremilk and hindmilk samples of OW/OB. Despite this, DHA (ω3 PUFA) levels in OW/OB women were similar in foremilk and significantly decreased in hindmilk samples as compared to normal BMI women. Consequently, the ratio of DHA/Total ω3 significantly decreased in foremilk and hindmilk samples of OW/OB women. However, proinflammatory AA (ω6 PUFA) levels increased, resulting in an increased ratio of AA/DHA in OW/OB women. Breast milk DHA was positively correlated, whereas AA was negatively correlated with maternal plasma. Conclusions: Marked differences in maternal plasma and breast milk ω3 and ω6 FA concentrations among women with OW/OB indicate significant differences in nutritional exposures for their infants. Reduced milk DHA may be a consequence of reduced mammary peroxisomal conversion of ALA to DHA due to increased insulin/reactive species within the maternal obese environment. The imbalance of ω3 and ω6 FAs suggests that DHA supplementation and approaches to limit plasma to breast milk AA transfer in OW/OB subjects may be of value. Full article

Background/Objectives: Medium-chain fatty acids (MCFAs), abundant in coconut oil, have attracted considerable attention in recent years owing to their potential impact on muscle atrophy. However, the mechanisms underlying their effects remain inadequately understood. This study aimed to examine the impact of coconut-oil-derived MCFAs on skeletal muscle in a mouse model administered a high-fat diet. Methods: C57BL/6J mice were assigned to a normal diet, lard diet, or coconut oil diet and maintained for a duration of 12 weeks. A glucose tolerance test was conducted, and biochemical parameters, muscle histological analysis, and gene expression in muscle tissue were assessed. MCFA concentrations in serum and muscle were quantified utilizing gas chromatography–mass spectrometry. An in vitro experiment was conducted by treating mouse C2C12 myotube cells with lauric acid and palmitic acid, followed by a gene expression evaluation. Results: Mice fed a coconut-oil-based diet exhibited reduced body weight gain and lower blood glucose and total cholesterol levels compared to those fed a lard-based diet. The coconut-oil-fed group showed increased concentrations of MCFAs in both serum and muscle tissue, along with an improvement in relative grip strength. The expression levels of proteins and genes associated with muscle atrophy were reduced in muscle tissue. These findings were corroborated in vitro using C2C12 myotube cells. Conclusions: Coconut oil may preserve muscle strength by increasing MCFA concentrations in serum and muscle tissue, while suppressing the expression of muscle-atrophy-related proteins and genes. These findings suggest that coconut oil may be beneficial in preventing muscle atrophy induced by long-chain fatty acids. Full article

Background: Dietary patterns impact blood pressure (BP) levels, but the potential impact of replacing specific types of fats with proteins or carbohydrates, in isocaloric models, on BP remains unclear. Objective: This study evaluates the longitudinal association between the substitution of different types of fats with proteins or carbohydrates and changes in BP in a Mexican population. Methods: We analyzed data from 1448 adults (mean age at baseline: 45 years; 73.3% women) from the Health Workers Cohort Study, followed over 13 years. Trained personnel measured systolic (SBP) and diastolic (DBP) blood pressure following standard procedures and techniques at baseline and follow-up. Macronutrient intake was assessed with a validated semi-quantitative food frequency questionnaire. Generalized Estimating Equations (GEE) for hypertension and fixed-effects linear regression for BP were conducted using isocaloric substitution models. Each estimate reflects the effect of a 3% energy substitution of specific fats for carbohydrates or proteins. Results: Substituting 3% of energy intake of polyunsaturated fat (PUFA) in place of vegetable protein (β = −2.94, 95% CI: −5.02, −0.86), animal protein (β = −2.68, 95% CI: −4.73, −0.63), low glycemic index (LGI) carbohydrates (β = −2.63, 95% CI: −4.40, −0.86), and high glycemic index (HGI) carbohydrates (β = −2.52, 95% CI: −4.31, −0.74) was associated with a significant reduction in SBP. Substituting 3% of the energy intake of PUFA in place of different types of carbohydrates was associated with lower odds of hypertension. PUFA was not associated with changes in DBP. Conclusions: Our findings suggest that exchanging PUFA for carbohydrates or proteins is associated with reduced SBP and a lower risk of hypertension, highlighting the importance of macronutrient composition independent of total energy intake and other fat types, which may have a substantial impact at the population level. Full article

Background/Objectives: Chronic inflammation is recognized as an important risk factor for a variety of health disorders. Omega-6 polyunsaturated fatty acids (n-6 PUFAs), particularly linoleic (LA) and arachidonic acid (AA), have been shown to be either pro- or anti-inflammatory, and researchers have advocated both for and against reducing their dietary intake. This study sought to correlate the levels of ten inflammation-related biomarkers across multiple pathways with red blood cell (RBC) membrane levels of the major dietary and circulating n-6 PUFAs. Methods: We included 2777 participants (mean age: 66 ± 9 years, 54% women, 9.8% minorities) from the Framingham Offspring and minority-enriched Omni cohorts, and calculated partial correlation coefficients. Results: After multivariable adjustment, RBC LA was inversely correlated (all p ≤ 0.05) with five markers of inflammation, receptors, or pathways: C-reactive protein (r = −0.06); soluble interleukin-6 (r = −0.15); intercellular adhesion molecule-1 (r = −0.09); monocyte chemoattractant protein-1 (r = −0.07); and P-selectin (r = −0.07). RBC AA was inversely correlated (all p ≤ 0.05) with soluble interleukin-6 (r = −0.10); intercellular adhesion molecule-1 (r = −0.14); monocyte chemoattractant protein-1, and (r = −0.06); and osteoprotegerin (r = −0.07). Lipoprotein-associated phospholipase-A2 mass and activity, urinary isoprostanes, and tumor necrosis factor receptor-2 were not significantly correlated with LA or AA. Conclusions: In our large community-based study, we observed weak but statistically significant inverse associations between several types of inflammatory biomarkers with RBC n-6 PUFAs. Our findings do not support the hypothesis that omega-6 fatty acids are pro-inflammatory. Full article

Objectives: This study analyzed correlations of colostrum fatty acids (FAs), newborns’ and mothers’ thyroid hormones (THs), and birth weight, all crucially important in neonatal health. Methods: LC-MS/MS was used to measure 22 FAs in the colostrum of 78 healthy mothers who delivered term babies. FT3, FT4, and TSH levels were determined in the mothers’ serum, and newborns’ TSH was measured in heel-pricked specimens. Correlations were defined in the whole cohort and the subsets, which were separated according to ranges of birth weight, thyroid hormones, and mothers’ body mass index. Phyton Software was used for statistics. Results: The colostrum’s total FA content was highly variable and correlated positively with the percentage values of arachidic, gondoic, and nervonic acids. Five FAs all positively correlated with birth weight for the entire cohort—including ω9 gondoic, erucic, and nervonic acids as well as saturated behenic and lignoceric acids—all produced with the same elongases. These correlations were relevant to gondoic, nervonic, behenic, and lignoceric acids when mothers with low FT4 levels were evaluated separately and to erucic acid in the subset comprising mothers with high TSH values. Conclusions: The priming of breast epithelia to adjust the colostrum quality starts prenatally, whose regulatory mechanisms partially overlap with fetal fat accretion. Thus, colostrum content may undergo modifications to compensate for the harm of subtle TH deficiencies on neonates’ thermoregulation and development. Considering the previous findings showing that milk ω9 FAs are highest in colostrum, and even higher when mothers deliver preterm, our current results indicate their possible protective functions. Full article

Background/Objectives: Familial hypercholesterolemia (FH) is an increasingly common inherited disorder that increases cardiovascular risk. Despite the importance of lifestyle interventions, adherence to a healthy diet among individuals with FH remains suboptimal. This pilot, multicenter, double-blind, placebo-controlled randomized trial aimed to evaluate the feasibility and preliminary effects of a culturally adapted cardioprotective diet (DICA-FH), alone or in combination with phytosterol and/or krill oil supplementation, on lipid parameters in Brazilian adults with probable or definitive FH. Methods: Between May and August 2023, 58 participants were enrolled across nine Brazilian centers and randomized (1:1:1:1) into four groups: DICA-FH + phytosterol placebo + krill oil placebo; DICA-FH + phytosterol 2 g/day + krill oil placebo; DICA-FH + phytosterol placebo + krill oil 2 g/day; and DICA-FH + phytosterol 2 g/day + krill oil 2 g/day. Interventions lasted 120 days. The primary outcomes were mean low-density lipoprotein cholesterol (LDL-c) and lipoprotein(a) (Lp[a]) levels, as well as adherence to treatment at follow-up. Secondary outcomes included mean levels of other lipids, frequency of adverse events, and assessment of protocol implementation components. All data were presented separately for the allocation groups: phytosterol vs. placebo and krill oil vs. placebo. Results: Mean age was 54.5 ± 13.7 years, and 58.6% were women. Both adherence to protocol (91.8% attendance; 79.1% investigational product intake) and retention (86.2%) were high. No significant differences between groups were found for LDL-c or Lp(a). However, regardless of allocation to active supplementation or placebo, a significant reduction in Lp(a) concentrations was observed following the DICA-FH intervention (median difference: −3.8 mg/dL [interquartile range: −7.5 to −1.2]; p < 0.01). Significant reductions in oxidized LDL (LDL-ox) and LDL-ox/LDL-c ratio were also observed in the overall sample (p < 0.01). Although not statistically significant, all groups showed improvements in diet quality after 120 days. No serious adverse events related to the interventions were reported. Additionally, most protocol implementation components were successfully achieved. Conclusions: The DICA-FH strategy, with or without supplementation, was safe and well-tolerated. Although not powered to detect clinical efficacy (which is acceptable in exploratory pilot trials), the study supports the feasibility of a larger trial and highlights the potential of dietary interventions in the management of HF. Full article

Alginate oligosaccharide (AOS), a degradation product of alginate derived from marine brown algae, has attracted significant attention due to its potent ability to modulate gut microbiota and enhance human health. This review aims to systematically introduce current evidence on the interactions between AOS and gut microbial communities, focusing on how AOS improves health through regulating gut microbiota. Initially, the structural factors of AOS that influence their functions are highlighted, including molecular weight, monomer composition, terminal structure, and chemical modifications. Importantly, AOS primarily exerts beneficial effects by adjusting gut microbiota community and outputs, which include the promotion of probiotics, the inhibition of pathogens, the balance of microbiota composition, and the increase of short-chain fatty acid production. Moreover, the discovered mechanisms underlying AOS-mediated health promotion via microbiota modulation are detailed comprehensively, specifically emphasizing intestinal barrier maintenance, antioxidation, dual-regulation of immune and inflammatory responses, pathogenic infection inhibition, metabolic improvement, uric acid excretion promotion, anti-tumor effects, and anti-skin aging. Such beneficial effects make AOS valuable in keeping healthy, preventing disorders, and intervening in diseases. Despite these findings and research progress, there are yet limitations in studying AOS–gut microbiota interactions, such as precise microbiota-targeted structural optimization, personalized nutritional interventions based on microbial characteristics, and broadening the horizon of microbiota-derived metabolic metabolomic profiles. In conclusion, advancing our understanding of the gut microbiota-centered mechanisms of AOS would probably facilitate novel nutritional strategy development for health promotion. Full article