Journal of Nutritional Biochemistry最新文献

Naringenin is a plant-derived flavonoid having anti-proliferative, anti-inflammatory, and anti-angiogenic properties against various metabolic disorders. Though there are reports demonstrating the osteogenic potential of naringenin, its effect remains largely unexplored in senile osteoporosis. The current study was planned with the objective to demonstrate the osteoprotective effect of naringenin in conditions of senile osteoporosis induced by D-galactose (D-gal). The results in the D-gal aging bone loss animal model suggest that naringenin improves bone microarchitecture, promotes ex-vivo mineralization, and alters bone serum markers. To check the mode of action of naringenin behind its protective effect, further experiments were performed at the cellular level. Naringenin facilitates osteoblast differentiation and suppresses osteoblast senescence, apoptosis, and cellular reactive oxygen species (ROS) production in primary osteoblast cells after D-gal stimulation. Mechanistically, naringenin mitigates senescence through the estrogen receptor-mediated pathway, as confirmed when calvarial osteoblast cells treated with ICI182.780, an estrogen pathway inhibitor, greatly decrease its effectiveness. Taken together, these results lead us to conclude that naringenin may function as a potential therapeutic agent for senile osteoporosis.

Sulforaphane (SFN), an isothiocyanate derived from cruciferous vegetables, has shown therapeutic potential in inflammatory diseases. Our previous studies demonstrated that SFN ameliorates ulcerative colitis (UC) and restores gut microbiota composition in dextran sulfate sodium (DSS)-induced mice. In the present study, we further investigate the protective effects and underlying mechanisms of SFN against secondary liver injury associated with UC. The results revealed that SFN significantly alleviated pathological damage in both the colon and liver, improved liver function parameters, upregulated intestinal tight junction proteins and Muc2 expression, and inhibited inflammation in DSS-induced colitis mice. Additionally, SFN significantly elevated short-chain fatty acid (SCFA) concentrations, enhanced the expression of SCFA receptors (free fatty acid receptors 2 and 3, FFAR2/3), and modulated macrophage polarization by inhibiting M1 and promoting M2 phenotypes in the colon and liver. Collectively, these findings suggest that SFN may alleviate colitis and secondary liver injury by enhancing intestinal barrier function and reducing inflammatory responses, potentially via the SCFAs-FFAR2/3-macrophage polarization signaling cascade. Thus, SFN may serve as a promising adjunctive therapeutic agent for the prevention and treatment of UC.

Determining dietary energy and protein level to accelerate heifer growth while ensuring mammary development remains challenging. Technical and economic constraints in cattle hinder defining optimal energy protein levels and breeding timing. Thus, we used mice as a model to examine how post-weaning diets differing in energy and protein concentrations, combined with two breeding strategies, affect mammary development and lactation. 240 female mice (21 d) were divided into five dietary groups: high-energy moderate-protein (HM), high-energy low-protein (HL), moderate-energy moderate-protein (MM), low-energy moderate-protein (LM) and low-energy low-protein (LL). Mammary tissue and serum were collected at target mating weight (27 ± 1 g) and body maturity (56 days). Breeding was initiated either upon attainment of target weight or at 63 days of age, with collection of mammary and serum samples at gestation 15d as well as serum samples at lactation 13d. The results showed that moderate increases in dietary energy accelerate growth, enhance mammary development, and improve lactational performance in mice. Under low-energy intake, maintaining adequate protein is critical for mammary and overall growth. High-energy feeding combined with a weight-based mating strategy markedly increased milk yield, whereas age-based mating provided nutrient-restricted mice with the necessary developmental window. These findings provide a theoretical foundation for advancing age at first calving through high energy feeding strategies in heifer management.

Skeletal muscle is the primary storage and metabolic site for amino acids and proteins in the body, and its mass and function are affected by various pathological factors. Studies have shown that mitochondrial dysfunction is associated with skeletal muscle atrophy. Indole-3-carbinol (I3C) and its active metabolite 3,3'-Diindolylmethane (DIM) have bioactivities such as inhibiting fat formation, but it is unclear whether they can affect skeletal muscle atrophy in obesity by improving mitochondrial function. Our research found that high-fat factors can induce obesity-related skeletal muscle atrophy, characterized by decreased muscle mass and function, reduced mitochondrial number, and impaired function in muscle cells. DIM can improve obesity-related skeletal muscle atrophy caused by a high-fat diet, and the mechanism may be related to the regulation of AMPK/SIRT1/PGC-1α pathway protein expression and improved mitochondrial function in muscle cells.

Glomerular podocytes injury represents a critical pathological hallmark of diabetic kidney disease (DKD), in which lipotoxicity plays a central pathogenic role. Our previous investigations in type 2 diabetes mellitus (T2DM) have demonstrated that Jujuboside A (Ju A), a triterpene saponin isolated from Semen Ziziphi Spinosae (SZS), exerted dual therapeutic effects in T2DM by ameliorating hepatic steatosis and renal dysfunction. However, the role of podocytes lipid metabolism in Ju A-mediated protection against DKD remain undefined prior to the present study. In this work, we reported that Ju A significantly attenuated glomerular podocytes injury and lipotoxicity in DKD, while concurrently improving renal function and preserving glomerular morphology. Mechanistically, Yin Yang 1 (YY1)-mediated alleviation of lipotoxicity contributed to the protective effect of Ju A against glomerular podocytes injury, primarily by promoting intracellular cholesterol transport and efflux. In conclusion, our findings demonstrated that Ju A mitigated lipid overload in glomerular podocytes by modulating cholesterol homeostasis via YY1, which not only intercepted the pathological progression of DKD but also provided a potential therapeutic target (YY1) and candidate agent (Ju A) for DKD intervention.

The rising global prevalence of obesity and its impact on health and economy make finding available safe treatment an urgent need. Ketogenic diet represents trendy dietary intervention, while underlying molecular mechanisms remains unclear. Twenty-four male Sprague-Dawley rats were randomized into three groups: Control (maintained on conventional chow diet for 24 weeks), HFD (fed High-fat diet (HFD) for 24 weeks), keto (fed HFD for 12 weeks, then ketogenic diet for additional 12 weeks). Effect of ketogenic diet on serum metabolomics using Ultra Performance Liquid Chromatography coupled with Liquid Chromatography on both positive and negative modes; hepatic tissue using histopathological examination, enzyme-linked immunosorbent assay (ELISA), Real time Polymerase Chain Reaction, proteome array detection; intestinal tissue using histopathological examination, ELISA and adipose tissue using histopathological examination were evaluated. The ketogenic diet reduced rat weight, food intake, epididymal fat mass, and blood glucose level compared to HFD group. Furthermore, it resulted in a decrease in serum methionine, linolenic acid, Lyso Phosphatidylcholine (PC) (15.0:0.0), Lyso PC (18.0:0.0) with hepatic repression of fibroblast growth factor 21 (FGF21), and type II cell surface protein/ Dipeptidyl peptidase 4, Intercellular Adhesion Molecule 1, Insulin growth factor-1, Lipocalin-2, Serpin E1, tissue inhibitor of matrix metalloproteinase-1, receptor for advanced glycation end products and induction of Farnesoid X receptor (FXR), hepatocyte growth factor (HGF) which leads to hepatic antioxidant effects and histopathological amelioration. In addition, the ketogenic diet caused intestinal induction of melanocortin-4 receptors/ glucagon-like peptide 1 pathway, which causes intestinal antioxidant effects and histopathological amelioration. Thus, ketogenic diet stated potential anti-obesity effect that mitigates HFD-induced organ damage through the modulation of key metabolic and signaling networks.

The gut microbiota plays an important role in host health and dysbiosis contributes to disease development. Natural forms of vitamin E consist of eight lipophilic antioxidants, i.e., alpha-, beta-. gamma- and delta-tocopherol (αT, βT, γT and δT) and alpha-, beta-. gamma- and delta-tocotrienol (αTE, βTE, γTE and δTE). Vitamin E forms and their metabolites including 13'-carboxychromanols (13'-COOHs) have been shown to possess anti-inflammatory activities. Interestingly, recent human and animal studies reveal that vitamin E forms and δTE-13'-COOH (metabolite of δTE) can modulate gut microbiota. Specifically, supplementation of αT, γT, tocotrienols or δTE-13'-COOH elevated some beneficial bacteria or attenuated disease-associated decrease of probiotics including butyrate producers. This review focuses on the current knowledge of the effects of different forms of vitamin E and δTE-13'-COOH on gut microbiome. Although the mechanisms underlying modulation of gut microbiota remain to be determined, this author proposes that promotion of beneficial gut microbes by vitamin E forms may in part be rooted in their antioxidant and anti-inflammatory activities as well as protection of intestinal barrier integrity, and that the modulatory effects on gut microbes likely contributes to vitamin E-facilitated disease prevention. Finally, this review discusses knowledge gaps and future research efforts needed to uncover how vitamin E forms interact with gut microbiota and utilize such knowledge for improving human health.

Among the many macro- and micronutrients contained in cow's milk, one of the most important is the lipid fraction. While the nutritional and physiological benefits of milk consumption after the first years of life are the subject of some debate, there also appear to be conflicting views on the health aspects of the milk lipids, including their involvement in cancer. Positive in vitro and/or in vivo data on growth-inhibiting or cytotoxic effects are available for lipid components of milk such as sphingomyelins and their degradation products or various hydroxy fatty acids. Isomers of linoleic acid and branched chain fatty acids have also been shown to have anticarcinogenic potential in animal models by inducing apoptosis. On the other hand, there is evidence of an association between increased cancer mortality and the consumption of high-fat milk, which contradicts the tumor protecting effects observed in vitro and in vivo. Consumption of high-fat dairy products appears to be associated with an increased risk of developing types of cancer compared to low-fat dairy or other topical soy-based alternatives. There are ambiguous results for an anticarcinogenic effect of various lipid constituents of cow's milk as well as for an association between general milk fat consumption and the occurrence especially of breast, colorectal, and prostate tumors. Whether the effects observed in epidemiological studies can be attributed to milk lipids or whether the promising preclinical data on their anti-cancer efficacy can be transferred to humans remains unclear at present, therefore this review summarizes the latest findings.

Gestational diabetes mellitus (GDM) is a prevalent complication, affecting approximately 14% of pregnancies worldwide, and is associated with an elevated risk of both maternal and infant complications. It also exerts long-term adverse effects on offspring health, including metabolic, cardiovascular, and neurodevelopmental disorders, thereby compromising maternal and infant well-being. During pregnancy, an imbalance between folic acid and vitamin B12 has been linked to an increased risk of GDM and unfavorable metabolic outcomes in offspring, underscoring the potential clinical value of maintaining their balance and implementing early interventions. This review summarizes the role of folic acid and vitamin B12 in gestational diabetes and offspring development, aiming to bridge the gap between mechanistic insights and clinical evidence. It highlights the potential for reverse causality in linking vitamin B12-folate imbalance to GDM risk and underscores the need to integrate novel metabolic and epigenetic concepts into future intervention trials.

Aortic aneurysm and dissection (AAD) is a life-threatening cardiovascular disorder with no currently available targeted therapies, underscoring the critical need for effective preventive strategies. Through integrative analysis of the UK Biobank and FooDB databases, we identified chlorogenic acid (CGA) - a natural polyphenol abundant in coffee and tea - as a potential protective compound against AAD. Using two mouse models of AAD-β-aminopropionitrile (BAPN) plus angiotensin II (Ang II) in 4-week-old wild-type mice and erythropoietin (EPO)-induced AAD in 8-week-old wild-type mice, we demonstrated that CGA administration significantly reduced AAD incidence, mortality, and aortic wall damage. Mechanistically, we discovered that the large neutral amino acid transporter 3 (LAT3) plays a pivotal role in AAD pathogenesis by mediating excessive branched-chain amino acids (BCAAs) uptake into vascular smooth muscle cells (SMCs). Dysregulated BCAAs metabolism led to intracellular BCAAs accumulation and hyperactivation of the mTOR signalling pathway, driving SMCs reprogramming and promoting AAD development. Crucially, CGA directly targeted and inhibited LAT3, thereby normalizing BCAA metabolism and suppressing mTOR activity, which mitigated AAD progression. Our findings not only reveal the therapeutic potential of CGA in AAD prevention but also identify the LAT3/BCAA/mTOR axis as a novel mechanistic target for AAD intervention.