Journal of Nutritional Biochemistry最新文献

Introduction: Brown adipose tissue (BAT) exhibits greater resilience against inflammation compared to white adipose tissue. However, chronic consumption of a high-fat diet can render brown adipocytes vulnerable to pro-inflammatory conditions, leading to a decline in their thermogenic capacity and subsequent dysfunction. The analysis of the effects of type fatty acids intake must be important in the context of the dietary pattern and obesity.

Objectives: This study aims to investigate the impact of a low-carbohydrate/high-fat diet, enriched with different types of fatty acids, on mitochondrial activity on brown adipose tissue in obese mice.

Methods: Male mice were allocated into different dietary groups: a control diet (CTL), and a high-fat diet (HFD) for a duration of 10 weeks to induce obesity. Subsequently, the HFD group was subdivided into the following categories for an additional 6 weeks: HFD with a low carbohydrate content enriched with saturated fatty acids; HFD with a low carbohydrate content enriched with fish oil; HFD with a low carbohydrate content enriched with soybean oil; and HFD with a low carbohydrate content enriched with olive oil.

Results: The findings indicated that in comparison to a low-carbohydrate diet rich in saturated fats, diets rich in unsaturated fatty acids-particularly omega-6 (n-6) and omega-9 (n-9)-resulted in elevated expression of UCP1, a marker of BAT activity. Moreover, there was an increase in the expression of PGC1-α, a protein involved in mitochondrial biogenesis, and enhanced functionality of the oxidative phosphorylation system within BAT mitochondria. These results suggest that n-6 and n-9 fatty acids may confer greater benefits to BAT functionality than saturated fats within the context of a low-carbohydrate diet. Therefore, this study revealed some molecular components that mediate BAT mitochondria function influenced by different fatty acids in a low carbohydrate diet, making it an important therapeutic target in obesity.

Numerous dietary phytochemicals such as curcumin, lutein and isoflavones are associated with health beneficial activities, however their application is often limited by their low bioavailability. Therefore, bioenhancers represent a feasible approach to increase the absorption efficiency of bioactive compounds. Here, we combined uptake and transport studies in differentiated Caco-2 cells with high resolution analytics and fractionation to evaluate the impact of spearmint (Mentha spicata) on the cellular uptake of curcumin. Additionally, we utilized mechanistic studies in native and overexpressing cell systems to assess P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) efflux transporter activity as well as in-silico molecular docking simulations. We found significantly elevated intracellular curcuminoid levels mediated by spearmint. Fractionation and functional assays identified (R)-(-)-carvone as a putative candidate for the biologically active compound mediating increased curcumin uptake via BCRP inhibition. Inhibition of P-gp-mediated efflux might additionally be involved. Molecular docking simulations suggest a common binding site of curcumin and (R)-(-)-carvone in BCRP. Further, spearmint significantly increased cellular uptake of lutein and transintestinal transport of isoflavones in-vitro. In summary, spearmint was identified as a novel bioenhancer for curcumin, lutein and isoflavones. Our findings suggest that spearmint increases bioavailability of a wide range of nutrients and drugs at least partially due to interference with BCRP via its active compound (R)-(-)-carvone.

The etiology of bone loss in celiac disease (CeD) remains a clinical challenge, with uncertainties present such as the extent of involvement of malabsorption and inflammation-induced osteoresorption processes in development of osteopenia/osteoporosis (OPN/OP), or reasons for failure to achieve healthy bone mass (BMD) even after long-term gluten-free diet (GFD) treatment. This observational prospective study explores the in vitro osteoclastogenic potential of peripheral blood precursors originating from adult active (newly diagnosed and untreated) celiac disease patients (aCeD) and describes the longitudinal changes in osteoclastogenesis after long-term adherence to GFD. To find connections between in vitro observations and in vivo bone metabolism changes, serum levels of 25(OH)D3, PTH, bCTX, PINP, CRP, IL-6, RANKL and OPG were measured before and after GFD and levels of these markers were correlated with the rate of osteoclastogenesis in vitro. OPG and IL-6 showed associations with BMD and/or presence of OPN/OP. Patients after GFD (CeD-GFD) exhibited improved BMD and increased serum 25(OH)D3 levels, alongside reduced bCTX and PINP levels. Compared to healthy donors, aCeD osteoclast genesis in vitro was higher and, surprisingly, remained elevated even in CeD-GFD patients. Negative correlation was found between osteoclastogenesis rate and serum OPG in aCeD, while osteoclastogenesis rate positively correlated with PTH in CeD-GFD. These results highlight OPG as marker for risk of OPN/OP in CeD and suggest that improvement of BMD after GFD is a result of uncoupling between bone metabolism and osteoresorptive action of osteoclasts after GFD.

While the plasma phylloquinone (PK) concentration is inversely correlated with cardiovascular risk, the involvement of PK in regulating endothelial function has not been directly investigated. Therefore, in this study we assessed the effects of short-term treatment with PK-deficient diets (5-10 weeks) on endothelial function in normolipidemic 14-week-old male C57BL/6JCmd mice and age-matched dyslipidaemic male E3L.CETP mice. Our results show that in normolipidemic mice dietary PK deficiency was associated with a marked reduction of PK levels in the plasma and liver (liquid chromatography-mass spectrometry measurements) and with impaired endothelium-dependent vasodilation assessed in vivo by magnetic resonance imaging (MRI). Dietary PK deficiency-induced endothelial dysfunction was fully reversed by PK supplementation. In dyslipidaemic E3L.CETP mice, dietary PK deficiency exacerbated preexisting endothelial dysfunction. Furthermore, dietary PK deficiency decreased menaquinone-4 (MK-4) levels in the aorta but did not affect blood coagulation (calibrated automated thrombography), microbiota composition (culturing and next-generation sequencing), and gut menaquinone production. In conclusion, our study demonstrated for the first time that sufficient dietary PK intake supports endothelial function in normolipidemic and dyslipidaemic mice indicating nutritional significance of dietary PK in the maintenance of endothelial function in humans.

Coffee brew is an integral part of the individual diet worldwide. Roasted coffee contains numerous bioactive substances whose significance for health is investigated in nutritional studies. Food biomarkers are recommended to correlate coffee consumption and health effects in the most unbiased way possible. Metabolites of atractyligenin derivatives from roasted coffee have been suggested as candidate analytes indicating coffee consumption. UHPLC-MS/MS analysis revealed that atractyligenin (1), 2-O-β-D-glucosylatractyligenin and 3'-O-β-D-glucosyl-2'-O-isovaleryl-2-O-β-D-glucosylatractyligenin were extracted into coffee brew. Their concentrations in filtered and unfiltered coffee did not differ significantly, suggesting independence from the preparation method. In a coffee intervention study (n=12, female/male 6/6), atractyligenin metabolites were not detectable in plasma after three days of coffee abstinence. After coffee, atractyligenin (1) and atractyligenin-19-O-D-glucuronide (M1) were the quantitatively dominant atractyligenin metabolites in plasma and showed two peaks each after 0.5 and 10 h, respectively. Half-lives after the first cmax in plasma were ∼0.31 h. 1 and M1 were detectable in plasma, indicating coffee consumption for up to 24 h after one serving. Within 10 h, ∼13.7% of the atractyligenin glycosides supplied by coffee brew were excreted in urine as metabolites 1 and M1. Metabolites 2β-hydroxy-15-oxoatractylan-4α-carboxy-19-O-β-d-glucuronide (M2) and 2β-hydroxy-15-oxoatractylan-4α-carboxylic acid-2-O-β-d-glucuronide (M3) were detected in only some samples and appeared unreliable as indicators for coffee consumption. No concentration differences between female and male study participants were observed in plasma and urine. In conclusion atractyligenin and its 19-O-β-D-glucuronide are promising markers of Arabica coffee consumption in plasma and urine for both men and women, independent of the brewing method.

Naringin, a flavonoid, has high antioxidant activity and hypolipidemic pharmacological effects. In this study, an animal model of dyslipidemia was established by feeding Apoe^-/- mice a high-fat diet for 4 weeks. Subsequently, the mice were administered Naringin via gavage at doses of 50 mg/(kg·d), 100 mg/(kg·d), or 200 mg/(kg·d) for an additional 4 weeks. The research utilized liquid chromatography-mass spectrometry (LC-MS) metabolomics in conjunction with analyses of serum oxidative stress markers, Hematoxylin-eosin staining, Masson's trichome staining, and immunohistochemical staining. Naringin treatment reduced serum total cholesterol, triglycerides, and low-density lipoprotein cholesterol concentrations (P<0.05), reversed disorders of vascular structure and morphology, increased serum nicotinamide adenine dinucleotide phosphate hydride and glutathione concentrations (P<0.05), reduced serum peroxynitrite concentrations (P<0.05), promoted aortic endothelial nitric oxide synthase protein expression and inhibited aortic prolyl isomerase-1 protein expression. Twenty differentiated metabolites were obtained from the serum by LC-MS assay, followed by 16 differential metabolic pathways after enrichment. Among the metabolic pathways, glycolysis/gluconeogenesis, the pentose phosphate pathway, purine metabolism, ascorbate metabolism, and aldarate metabolism are the most relevant metabolic pathways by which naringin reduces oxidative stress. Our findings suggest that naringin can reduce oxidative stress levels associated with dyslipidemia through multiple metabolic pathways, protect vascular endothelial function, and thus providing a novel and promising natural medicine for treating dyslipidemia.

Fruits and vegetables contain biologically active phenolic compounds that show mitigating effects against free radical damage and inflammation. The unique properties of phenolic compounds are protection against oxidative stress, and inception and potentiating of inflammation in the body. Aging is manifest with changes in epigenetic modifications and as with living systems undergo entropy. The gradual decline of body functions and in many cases with aging the cellular processes of senescence are contributors to age-related diseases. Herein the focus is on phenolic compounds as a diet approach to delay the negative consequences of aging. The actions of phenolic compounds on the biology of aging and senescence are presented. The phenolic compounds called flavonoids which are found in many fruits are potential anti-senescence factors that benefit health by reducing damage to DNA and the senescence-associated phenotypic cell changes in healthy cells during aging. Flavonoids are proposed to delay and palliate aging where senescence is involved. The dietary sources of natural phenolic compounds afford protection in the aging process and include as some examples naringenin, hesperidin, quercetin, kaempferol, luteolin, genistein, epigallocatechin gallate, and resveratrol. Many of these compounds possess anti-senescence effects. The purpose of the review is to discuss where food flavonoids interact with the targets of senescence and how these compounds can attenuate aging-related events. The goal is to provide greater insight into dietary flavonoids and how they improve health and lower the consequences of aging. A novel aspect of this review is the application of flavonoids to neuroprotective effects in brain to reduce pain and improve health with aging.