Journal of Nutritional Biochemistry最新文献

Gestational diabetes mellitus (GDM) is prevalent among pregnant individuals and is linked to increased risks for both mothers and fetuses. Although GDM is known to cause disruptions in gut microbiota and metabolites, their potential transmission to the fetus has not been fully explored. This study aimed to characterize the similarities in microbial and metabolic signatures between mothers with GDM and their neonates as well as the interactions between these signatures. This study included 89 maternal-neonate pairs (44 in the GDM group and 45 in the normoglycemic group). We utilized 16S rRNA gene sequencing and untargeted metabolomics to analyze the gut microbiota and plasma metabolomics of mothers and neonates. Integrative analyses were performed to elucidate the interactions between these omics. Distinct microbial and metabolic signatures were observed in GDM mothers and their neonates compared to those in the normoglycemic group. Fourteen genera showed similar alterations across both groups. Metabolites linked to glucose, lipid, and energy metabolism were differentially influenced in GDM, with similar trends observed in both mothers and neonates in the GDM group. Network analysis indicated significant associations between Qipengyuania and metabolites related to bile acid metabolism in mothers and newborns. Furthermore, we observed a significant correlation between several genera and metabolites and clinical phenotypes in normoglycemic mothers and newborns, but these correlations were disrupted in the GDM group. Our findings suggest that GDM consistently affects both the microbiota and metabolome in mothers and neonates, thus elucidating the mechanism underlying metabolic transmission across generations. These insights contribute to knowledge regarding the multiomics interactions in GDM and underscore the need to further investigate the prenatal environmental impacts on offspring metabolism.

Myosteatosis occurs in response to excess circulating fatty acids and is associated with muscle dysfunction. This study aimed to characterize the sequence of events of lipid-induced toxicity within muscle cells and the role of polyunsaturated fatty acids (PUFA) as potential preventive factors. Myosteatosis was induced in C2C12 myotubes exposed to palmitic acid (PAL 500µM). Furthermore, cells were co-incubated with PUFA (α-linolenic acid = ALA, Eicosapentaenoic acid = EPA, Docosahexaenoic acid = DHA; Arachidonic acid = ARA) over a period of 48 h. Cell viability, morphology, and measures of lipid and protein metabolism were assessed at 6, 12, 24, and 48 h. We observed that myotube integrity was rapidly and progressively disrupted by PAL treatment after 12 h, ultimately leading to cell death (41.7% cell survival at 48 h, p < .05). Cell death did not occur in cells exposed to PAL+ARA and PAL+DHA. After 6 h of PAL treatment, an accumulation of large lipid droplets was observed within the cell (6 folds, p < .05). This was associated with an increase in ceramides (CER x3 fold change) and diacylglycerol (DAG x150 fold change) contents (p < .05). At the same time, insulin was no longer able to stimulate protein synthesis (p < .05) nor leverage autophagic flux (p < .05). DHA and ARA were able to completely reverse the defect in protein synthesis and partially modulate the accumulation of CER and DAG. These findings present new and intriguing research avenues in the field of muscle metabolism and nutrition, particularly in the context of aging, chronic muscle disorders, and insulin resistance.

Previously, we showed that restrictive diets, including ketogenic diet (KD), have an anti-inflammatory impact on the healthy gastrointestinal tract of mice. Afterward, we found that energy-restricting diets mitigate inflammation in the dextran sodium sulfate (DSS) colitis mouse model. The current study aimed to verify the impact of KD on DSS colitis and assess if the diet's fat composition influences the outcomes of the intervention.

Mice with mild chronic colitis were fed control chow, KD composed of long-chain triglycerides (KD LCT) or a KD containing a mix of LCT and medium-chain triglycerides (KD LCT/MCT).

KDs did not reverse DSS-enhanced gut permeability and shortening of the colon. Both KDs had a similar impact on liver, cecum, and spleen weight, villi and colon length, the thickness of muscularis externa, and expression of ZO-1 and occludin. On the contrary, body weight, glutathione (GSH) and taurine-GSH levels, GSH-S transferase (GST), and myeloperoxidase (MPO) activity, as well as an abundance of several fecal bacteria, all were differentially affected by the two types of KDs. When compared to the DSS control diet, reduction in colon mucosa cytokines expression was stronger in KD LCT than in the KD LCT/MCT group.

We conclude that the outcomes of the KD interventions in terms of potential therapeutical applications depend on lipid composition. KD LCT showed a strong positive impact on gut inflammation. A potential contribution of GSH to KD outcomes and a correlation between MPO activity and microbiota composition was identified.

Malnutrition is a complicated illness that affects people worldwide and is linked to higher death rates, a heightened vulnerability to infections, and delayed cognitive development. Experimental models have been constructed to comprehend the mechanisms associated with hunger. In this regard, the current study used two different types of food aiming to validate a murine model of malnutrition based on dietary restriction. The study was conducted with fifty-six Swiss male mice (eight-week-old) divided into eight groups (n=7 each) and fed the following experimental diets (10 weeks): Standard Diet (ST) ad libitum; ST 20% dietary restriction; ST 40% dietary restriction; ST 60% dietary restriction; AIN93-M diet ad libitum; AIN93-M 20% dietary restriction; AIN93-M 40% dietary restriction; AIN93-M 60% dietary restriction. Body, biochemical, and histological parameters were measured, and the restriction effects on genes related to oxidative stress (GPX1 and GPX4) in epididymal adipose tissue were evaluated. The results obtained showed that 20%, 40%, and 60% of dietary restrictions were able to reduce body weight when compared to controls, highlighting the accentuated weight loss in animals with 60% restrictions, especially those fed with AIN-93 M, which showed physical changes such as whitish skin and dull coat, voracious eating, and hunched posture. The present animal model also showed biochemical changes with hypoalbuminemia, as well as histological epididymal adipose tissue modulation. The presence of increased oxidative stress was observed when evaluating the GPX4 gene. Given the results, 60% food restriction using the AIN93-M diet was the best protocol for inducing malnutrition.

To investigate the effects of vitamin D status on cutaneous wound healing, C57BL/6J mice were fed diets with different vitamin D levels or injected intraperitoneally with 1α,25(OH)₂D₃. Dorsal skin wounds were created and wound edge tissues were collected on days 4, 7, 11, and 14 postwounding. The proliferation and migration of HaCaT cells treated with shVDR or 1α,25(OH)₂D₃ were assessed. Vitamin D deficiency (VDD) decreased wound closure and might delay inflammatory response, shown by slower inflammatory cell infiltration, decreased IL6 and TNF expression in early phase followed by an increase later. VDD might postpone epithelial-mesenchymal transition (EMT), initially characterized by higher epithelial markers and lower mesenchymal markers, followed by opposite appearance later. Dietary vitamin D supplementation and 1α,25(OH)₂D₃ intervention tended to accelerate EMT. Regarding extracellular matrix (ECM), VDD appeared to reduce collagen deposition on day 4 and downregulated fibronectin, COL3A1, and MMP9 expression early, followed by an increase later, together with an initial increase and subsequent decrease in Timp1 mRNA expression. Dietary vitamin D intervention promoted fibronectin and MMP9 expression on day 4 and then downregulated their expression on day 14. TGFb1/SMAD2/3 signaling seemed to be downregulated by VDD and upregulated by 1α,25(OH)₂D₃. In vitro, partial inhibition of VDR by shVDR tended to inhibit HaCaT cell proliferation and migration, EMT, and TGFb1/SMAD2/3 signaling, whereas 1α,25(OH)₂D₃ appeared to generate opposite effects. In conclusion, VDD hindered cutaneous wound healing, potentially due to impaired inflammatory response, delayed EMT, decreased ECM, and inhibited TGFb1/SMAD2/3 pathway. Vitamin D and 1α,25(OH)₂D₃ tended to enhance EMT and ECM.

The aim of this experiment was to elucidate the metabolic ramifications of tryptophan supplementation in the context of high-carbohydrate diet-feeding, which is important for improving feeding strategies in aquaculture in order to improve fish carbohydrate metabolism. Juvenile blunt snout bream with an initial mean body mass of 55.0±0.5 g were allocated to consume one of three experimental diets: CN, a normal diet with carbohydrate content of 30% (w/w); HC, a diet with high carbohydrate content of 43% (w/w); and HL, a high-carbohydrate diet to which 0.8% L-tryptophan (L-trp) had been added. These diets were fed for 8 weeks, and the effects of the carbohydrate and tryptophan contents of the diets were assessed.

Histological analysis using Hematoxylin and Eosin (H&E) and Oil Red O staining revealed that high-carbohydrate intake was associated with abnormal hepatocyte morphology and excessive liver lipid accumulation, which were notably ameliorated by tryptophan supplementation. A significant increase in plasma glucose, glucagon, AGEs (advanced glycation end products), triglycerides, total cholesterol, and a significant decrease in insulin and hepatic glycogen after a high-carbohydrate diet in terms of plasma indices, compared to the control group. Almost all of them were restored to the normal level in the HL group. The present study might preliminarily suggest that tryptophan supplementation ameliorates the imbalance in glucose metabolism of this species induced by a high-carbohydrate diet. Transcriptomics showed that glucose metabolism under high carbohydrate was mainly regulated by the PI3K-AKT signaling pathway. The mRNA expression and protein levels of GLUT2 also varied with this pathway, which would suggest that sustained activation of this pathway with the addition of tryptophan accelerates glucose transport and insulin secretion under high-carbohydrate diet. Subsequent GTT and ITT experiments have also demonstrated that tryptophan improves glucose tolerance and insulin tolerance in blunt snout bream on a high-carbohydrate diet.

In conclusion, these findings elucidate the positive regulatory effect of tryptophan on the PI3K-AKT-GLUT2 pathway under a high carbohydrate diet and provide a theoretical basis for the subsequent rational application of high carbohydrate diets in the future.

Hypoxia stress has been demonstrated to impede animal embryonic development, spermatogenesis, and lactation, leading to decreased animal production performance. However, the impact of hypoxia-induced activation of hypoxia inducible factor-1 (HIF-1) signaling on milk protein and fat synthesis remains unclear. L-leucine, a branched-chain amino acid, is known to modulate milk protein and fat synthesis. Therefore, our study aimed to evaluate the effect of L-leucine on milk protein and fat synthesis under hypoxic conditions and shed light on the molecular mechanism using an in vitro model. The results indicated that hypoxia treatment significantly decreased the synthesis of α-casein and β-casein, as well as inhibited factors related to milk fat synthesis in bovine mammary epithelial cells (MAC-T). Additionally, hypoxia stress suppressed the activities of the mammalian target of rapamycin (mTOR) and protein kinase B (AKT). Interfering with HIF-1α significantly reversed the expression of AKT, mTOR and factors related to milk synthesis. Importantly, supplementation with L-leucine activated AKT/mTOR signaling, thereby enhancing milk protein and fat synthesis in MAC-T cells to some extent. In conclusion, these findings suggest that HIF-1 signaling plays an important role in milk synthesis and that L-leucine may stimulate the synthesis of milk protein and fat by activating the AKT/mTOR signaling pathway under hypoxic conditions, making it a potential additive for promoting milk synthesis inhibited by hypoxia.

Sunflower oil is one of the most commonly used fat sources in Argentina, and deep-fat frying is the popular food preparation process. The liver response of feeding a diet containing fried sunflower oil (SFOx) on growing rats was studied. Thirty-nine male weanling Wistar rats were randomly assigned to one of three diets for 8 wks: control (C), sunflower oil (SFO), and a diet containing SFOx, both of the sunflower diets were mixed with a commercial rat chow at weight ratio of 13% (w/w). Body weight and food consumption were recorded weekly. At t=8 wk, lipid profile and glycemia were measured. Visceral adiposity was registered. Liver was weighed and preserved for histological analysis, relative fatty acid profile, fibrosis markers and oxidative status.

The three diets did not alter body weights; however, the SFOx fed rats showed increased energy intake and visceral fat; therefore, in liver saturated fat content, trans fatty acids, plus other unidentified minor components, such as hydroperoxides, hydroxides, epidioxides, hydroperoxy epidioxides, hydroxylepidioxides, and epoxides, were detected. The hepatosomatic index of SFOx rats was altered and showed hepatic steatosis. SFOx rats exhibited increased liver dichlorodihydrofluorescein-diacetate and thiobarbituric acid substance levels and oxidized-proteins content. Their livers had lower relative levels of monounsaturated, polyunsaturated fatty acids and catalase activity, but matrix metalloproteinase-9 activity was unchanged.

Consumption of a diet rich in fried oil during growth could induce liver damage due to steatosis, excessive lipid toxicity and the accumulation of reactive oxygen species. Further progression could lead to hepatic fibrosis.

Air pollution is detrimental to pregnancy adversely affecting maternal and child health. Our objective was to unravel epigenetic mechanisms mediating the effect of preconception, periconception, and gestational exposure to inhaled air pollutants (AP) upon the maternal and placental-fetal phenotype and explore the benefit of an omega-3 rich dietary intervention. To this end, we investigated intranasal instilled AP during 8 weeks of preconception, periconception, and gestation (G; D0 to 18) upon GD16-19 maternal mouse metabolic status, placental nutrient transporters, placental-fetal size, and placental morphology. Prepregnant mice were glucose intolerant and insulin resistant, while pregnant mice were glucose intolerant but displayed no major placental macro-nutrient transporter changes, except for an increase in CD36. Placentas revealed inflammatory cellular infiltration with cellular edema, necrosis, hemorrhage, and an increase in fetal body weight. Upon examination of placental genome-wide epigenetic processes of DNA sequence specific 5′-hydroxymethylation (5′-hmC) and 5′-methylation (5′-mC) upon RNA sequenced gene expression profiles, revealed changes in key metabolic, inflammatory, transcriptional, and cellular processing genes and pathways. An omega-3 rich anti-inflammatory diet from preconception (8 weeks) through periconception and gestation (GD0-18), ameliorated all these maternal and placental-fetal adverse effects. We conclude that preconceptional, periconceptional and gestational exposures to AP incite a maternal inflammatory response resulting in features of pre-existing maternal diabetes mellitus with injury to the placental-fetal unit. DNA 5′-mC more than 5′-hmC mediated AP induced maternal inflammatory and metabolic dysregulation which together alter placental gene expression and phenotype. A dietary intervention partially reversing these adversities provides possibilities for a novel nutrigenomic therapeutic strategy.