Journal of Nutritional Biochemistry最新文献

In two previous studies, we showed that supplementing a high-fat (HF) diet with 9% w/w U. dioica protects against fat accumulation, insulin resistance, and dysbiosis. This follow-up study in C57BL6/J mice aimed at testing: (i) the efficacy of the vegetable at lower doses: 9%, 4%, and 2%, (ii) the impact on intestinal T and B cell phenotype and secretions, (iii) impact on fat and glucose absorption during excess nutrient provision. At all doses, the vegetable attenuated HF diet induced fat accumulation in the mesenteric, perirenal, retroperitoneal fat pads, and liver but not the epididymal fat pad. The 2% dose protected against insulin resistance, prevented HF diet-induced decreases in intestinal T cells, and IgA⁺ B cells and activated T regulatory cells (Tregs) when included both in the LF and HF diets. Increased Tregs correlated with reduced inflammation; prevented increases in IL6, IFNγ, and TNF$\alpha$ in intestine but not expression of TNF$\alpha$ in epididymal fat pad. Testing of nutrient absorption was performed in enteroids. Enteroids derived from mice fed the HF diet supplemented with U. dioica had reduced absorption of free fatty acids and glucose compared to enteroids from mice fed the HF diet only. In enteroids, the ethanolic extract of U. dioica attenuated fat absorption and downregulated the expression of the receptor CD36 which facilitates uptake of fatty acids. In conclusion, including U. dioica in a HF diet, attenuates fat accumulation, insulin resistance, and inflammation. This is achieved by preventing dysregulation of immune homeostasis and in the presence of excess fat, reducing fat and glucose absorption.

Along with the increasing prevalence of obesity worldwide, the deleterious effects of high-calorie diet are gradually recognized through more and more epidemiological studies. However, the concealed and chronic causality whitewashes its unhealthy character. Given an ingenious mechanism orchestrates the metabolic adaptation to high-fat high-fructose (HFF) diet and connive its lipotoxicity, in this study, an experimental rat/mouse model of obesity was induced and a comparative transcriptomic analysis was performed to probe the mystery. Our results demonstrated that HFF diet consumption altered the transcriptomic pattern as well as different high-calorie diet fed rat/mouse manifested distinct hepatic transcriptome. Validation with RT-qPCR and Western blotting confirmed that SREBP1-FASN involved in de novo lipogenesis partly mediated metabolic self-adaption. Moreover, hepatic ACSL1-CPT1A-CPT2 pathway involved in fatty acids β-oxidation, played a key role in the metabolic adaption to HFF. Collectively, our findings enrich the knowledge of the chronic adaptation mechanisms and also shed light on future investigations. Meanwhile, our results also suggest that efforts to restore the fatty acids metabolic fate could be a promising avenue to fight against obesity and associated steatosis and insulin resistance challenged by HFF diet.

Maternal obesity might induce obesity and metabolic alterations in the progeny. The study aimed to determine the effect of supplementing obese mothers with Mel (Mel) on thermogenesis and inflammation. C57BL/6 female mice (mothers) were fed from weaning to 12 weeks control diet (C, 17% kJ as fat) or a high-fat diet (HF, 49% kJ as fat) and then matted with male mice fed the control diet. Melatonin (10 mg/kg daily) was supplemented to mothers during gestation and lactation, forming the groups C, CMel, HF, and HFMel (n = 10/group). Twelve-week male offspring were studied (plasma biochemistry, immunohistochemistry, protein, and gene expressions at the hypothalamus - Hyp, subcutaneous white adipose tissue - sWAT, and interscapular brown adipose tissue - iBAT). Comparing HFMel vs. HF offspring, fat deposits and plasmatic proinflammatory markers decreased. Also, HFMel showed decreased Hyp proinflammatory markers and neuropeptide Y (anabolic) expression but improved proopiomelanocortin (catabolic) expression. Besides, HFMel sWAT adipocytes changed to a beige phenotype with-beta-3 adrenergic receptor and uncoupling protein-1 activation, concomitant with browning genes activation, triggering the iBAT thermogenic activity. In conclusion, compelling evidence indicated the beneficial effects of supplementing obese mothers with Mel on the health of their mature male offspring. Mel led to sWAT browning-related gene enhancement, increased iBAT thermogenis, and mitigated hypothalamic inflammation. Also, principal component analysis of the data significantly separated the untreated obese mother progeny from the progeny of treated obese mothers. If confirmed in humans, the findings encourage a future guideline recommending Mel supplementation during pregnancy and breastfeeding.

Brain plasticity and cognitive functions are tightly influenced by foods or nutrients, which determine a metabolic modulation having a long-term effect on health, involving also epigenetic mechanisms. Breast milk or formula based on cow milk is the first food for human beings, who, throughout their lives, are then exposed to different types of milk.

We previously demonstrated that rats fed with milk derived from distinct species, with different compositions and nutritional properties, display selective modulation of systemic metabolic and inflammatory profiles through changes of mitochondrial functions and redox state in liver, skeletal and cardiac muscle. Here, in a rat model, we demonstrated that isoenergetic supplementation of milk from cow (CM), donkey (DM) or human (HM) impacts mitochondrial functions and redox state in the brain cortex and cortical synapses, affecting neuroinflammation and synaptic plasticity. Interestingly, we found that the administration of different milk modulates DNA methylation in rat brain cortex and consequently affects gene expression. Our results emphasize the importance of nutrition in brain and synapse physiology, and highlight the key role played in this context by mitochondria, nutrient-sensitive organelles able to orchestrate metabolic and inflammatory responses.

Chemotherapy failure in colorectal cancer patients is the major cause of recurrence and poor prognosis. As a result, there is an urgent need to develop drugs that have a good chemotherapy effect while also being extremely safe. In this study, we found cafestol inhibited colon cancer growth and HCT116 proliferation in vivo and in vitro, and improved the composition of intestinal flora. Further metabolomic data showed that autophagy and AMPK pathways were involved in the process of cafestol's anti-colon cancer effects. The functional validation studies revealed that cafestol increased autophagy vesicles and LC3B-II levels. The autophagic flux induced by cafestol was prevented by using BafA1. The autophagy inhibitor 3-MA blocked the cafestol-induced increase in LC3B-II and cell proliferation inhibition. Then we found that cafestol induced the increased expressions of LKB1, AMPK, ULK1, p-LKB1, p-AMPK, and p-ULK1 proteins in vivo and in vitro. Using the siRNA targeted to the Lkb1 gene, the levels of AMPK, ULK1, and LC3B-II were suppressed under cafestol treatment. These results indicated that the effect of cafestol is through regulating LKB1/AMPK/ULK1 pathway-mediated autophagic death. Finally, a correlation matrix of the microbiome and autophagy-related proteins was conducted. We found that cafestol-induced autophagic protein expression was positively correlated with the beneficial intestinal bacteria (Muribaculaceae, Bacteroides, Prevotellacece, and Alloprevotella) and negatively correlated with the hazardous bacteria. Conclusions: This study found that cafestol inhibited colon cancer in vitro and in vivo by the mechanism that may be related to LKB1/AMPK/ULK1 pathway-mediated autophagic cell death and improved intestinal microenvironment.

Globally, neurodegeneration and cerebrovascular disease are common and growing causes of morbidity and mortality. Pathophysiology of this group of diseases encompasses various factors from oxidative stress to gut microbial dysbiosis. The study of the etiology and mechanisms of oxidative stress as well as gut dysbiosis-induced neurodegeneration in Alzheimer's disease, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, autism spectrum disorder, and Huntington's disease has recently received a lot of attention. Numerous studies lend credence to the notion that changes in the intestinal microbiota and enteric neuroimmune system have an impact on the initiation and severity of these diseases. The prebiotic role of polyphenols can influence the makeup of the gut microbiota in neurodegenerative disorders by modulating intracellular signalling pathways. Metabolites of polyphenols function directly as neurotransmitters by crossing the blood-brain barrier or indirectly via influencing the cerebrovascular system. This assessment aims to bring forth an interlink between the consumption of polyphenols biotransformed by gut microbiota which in turn modulate the gut microbial diversity and biochemical changes in the brain. This systematic review will further augment research towards the association of dietary polyphenols in the management of gut dysbiosis-associated neurodegenerative diseases.

Gustin, a trophic factor for taste bud development, and its polymorphism at rs2274333 influence taste perception of 6-n-propylthiouracil (PROP) and fungiform papillae (FP) density. The PROP taster status affects dietary fat sensing and body composition. However, there is a paucity of research on the gustin genotype with dietary fat perception, PROP tasting ability, and body mass index (BMI). Thus, taste sensitivity to fat and bitterness was evaluated in 178 healthy individuals. The general labeled magnitude scale was used to determine suprathreshold taste intensity ratings, whereas the alternative forced choice approach was used to estimate the taste-sensing ability. The FP density was assessed by applying blue-colored food dye over the anterior region of the tongue. Restriction fragment length polymorphism was used to detect the genetic polymorphism (rs2274333) in the carbonic anhydrase VI (CA-VI) gene. Fisher's chi-square analysis showed that the CA-VI genotype and allelic frequencies significantly correlated (p<0.001) with the PROP taster status and BMI. Healthy individuals with AA genotypes of the CA-VI polymorphism and PROP super-tasters demonstrated stronger gustatory sensitivity for linoleic acid (LA) with greater FP density in comparison to individuals with AG/GG genotypes and other PROP taster groups. Stepwise forward multiple regression analysis indicates that BMI and PROP taster status significantly influence the LA sensing ability. The suprathreshold intensity rating for LA was also significantly impacted by PROP taster status and CA-VI genotypes, with a variation of 73.3%. Overall, our findings show a relationship between the taste papillae environment and the CA-VI genetic mutation at rs2274333, which influenced the gustatory preference for dietary fat and bitter taste.