A high-fat diet promotes cancer progression by inducing gut microbiota–mediated leucine production and PMN-MDSC differentiation

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(20)

Published: May 6, 2024

A high-fat diet (HFD) is a high-risk factor for the malignant progression of cancers through disruption intestinal microbiota. However, role HFD-related gut microbiota in cancer development remains unclear. This study found that obesity and obesity-related were associated with poor prognosis advanced clinicopathological status female patients breast cancer. To investigate impact HFD-associated on progression, we established various models, including HFD feeding, fecal transplantation, antibiotic bacterial gavage, tumor-bearing mice. promotes by generating polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). Mechanistically, released abundant leucine, which activated mTORC1 signaling pathway myeloid progenitors PMN-MDSC differentiation. Clinically, elevated leucine level peripheral blood induced was correlated tumoral infiltration clinical outcomes These findings revealed “gut–bone marrow–tumor” axis involved HFD-mediated opens broad avenue anticancer therapeutic strategies targeting aberrant metabolism

Language: Английский

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Inter-organ metabolic interaction networks in non-alcoholic fatty liver disease

Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 9, 2025

Non-alcoholic fatty liver disease (NAFLD) is a multisystem metabolic disorder, marked by abnormal lipid accumulation and intricate inter-organ interactions, which contribute to systemic imbalances. NAFLD may progress through several stages, including simple steatosis (NAFL), non-alcoholic steatohepatitis (NASH), cirrhosis, potentially cancer. This closely associated with disorders driven overnutrition, key pathological processes dysregulation, impaired autophagy, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, local inflammation. While hepatic metabolism in well-documented, further research into communication mechanisms crucial for deeper understanding of progression. review delves intrahepatic networks tissue-specific signaling mediators involved pathogenesis, emphasizing their impact on distal organs.

Language: Английский

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Sugar-sweetened beverage intake, gut microbiota, circulating metabolites, and diabetes risk in Hispanic Community Health Study/Study of Latinos

Cell Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Fructose: a modulator of intestinal barrier function and hepatic health?

European Journal of Nutrition, Journal Year: 2023, Volume and Issue: 62(8), P. 3113 - 3124

Published: Aug. 18, 2023

Abstract Purpose Consumption of fructose has repeatedly been discussed to be a key factor in the development health disturbances such as hypertension, diabetes type 2, and non-alcoholic fatty liver disease. Despite intense research efforts, question if how high dietary intake interferes with human not yet fully answered. Results Studies suggest that besides its insulin-independent metabolism may also impact intestinal homeostasis barrier function. Indeed, it suggested by results animal well vitro studies enriched diets alter microbiota composition. Furthermore, have shown both acute chronic lead an increased formation nitric oxide loss tight junction proteins small tissue. These alterations related translocation pathogen-associated molecular patterns (PAMPs) like bacterial endotoxin induction dependent signaling cascades but other tissues. Conclusion In present narrative review, assessing effects on function their particular focus are summarized discussed.

Language: Английский

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Unravelling the Complex Relationship between Diet and Nephrolithiasis: The Role of Nutrigenomics and Nutrigenetics

Nutrients, Journal Year: 2022, Volume and Issue: 14(23), P. 4961 - 4961

Published: Nov. 23, 2022

Nephrolithiasis is an increasingly prevalent condition, especially in high income countries, and associated with morbidity. Extraordinary progress genetics made the identification of genetic forms nephrolithiasis possible. These diseases are usually rare do not account for most common that result several factors such as environment, dietary habits, predisposing genes. This knowledge has shaped what we classify nephrolithiasis, a condition now recognized systemic. How to extent all these interact one another end kidney stone formation, growth, recurrence completely understood. Two new research fields have recently been trying give some answers: nutrigenomics nutrigenetics. aim understanding intricate diet/genome interface influences gene expression regulation mainly through epigenetic mechanisms results specific medical conditions cancer, metabolic syndrome, cardiovascular diseases. Epigenetics seems play crucial role could represent link between environmental factors, constantly exposed to, risk nephrolithiasis. In this systematic review, summarize available evidence proven or hypothesized related

Language: Английский

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Recent Progress on Fructose Metabolism—Chrebp, Fructolysis, and Polyol Pathway

Nutrients, Journal Year: 2023, Volume and Issue: 15(7), P. 1778 - 1778

Published: April 5, 2023

Excess fructose intake is associated with obesity, fatty liver, tooth decay, cancer, and cardiovascular diseases. Even after the ingestion of fructose, concentration in portal blood never high; further metabolized 1/100th glucose concentration. It was previously thought that liver not small intestine, but it has been reported metabolism intestine also plays an important role metabolism. Glut5 knockout mice exhibit poor absorption. In addition, endogenous production via polyol pathway received attention; gene deletion aldose reductase (Ar), ketohexokinase (Khk), triokinase (Tkfc) found to prevent development fructose-induced lipidosis. Carbohydrate response element-binding protein (Chrebp) regulates expression Glut5, Khk, aldolase b, Tkfc. We review a focus on roles glucose-activating transcription factor Chrebp, fructolysis, pathway.

Language: Английский

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Gut microbiota in MAFLD: therapeutic and diagnostic implications

Therapeutic Advances in Endocrinology and Metabolism, Journal Year: 2024, Volume and Issue: 15

Published: Jan. 1, 2024

Metabolic dysfunction-associated fatty liver disease (MAFLD), formerly known as nonalcoholic disease, is becoming a significant contributor to chronic globally, surpassing other etiologies, such viral hepatitis. Prevention and early treatment strategies curb its growing prevalence are urgently required. Recent evidence suggests that targeting the gut microbiota may help treat alleviate progression in patients with MAFLD. This review aims explore complex relationship between MAFLD relation pathogenesis. Additionally, it delves into therapeutic microbiota, diet, exercise, antibiotics, probiotics, synbiotics, glucagon-like peptide-1 receptor agonists, fecal transplantation, discusses novel biomarkers, microbiota-derived testing liquid biopsy, for their diagnostic staging potential. Overall, emphasizes urgent need preventive address devastating consequences of at both individual societal levels recognizes further exploration open avenues managing effectively future.

Language: Английский

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Megalin knockout reduces SGLT2 expression and sensitizes to Western diet-induced kidney injury

Function, Journal Year: 2024, Volume and Issue: 5(4)

Published: Jan. 1, 2024

Abstract Megalin (Lrp2) is a multiligand receptor that drives endocytic flux in the kidney proximal tubule (PT) and necessary for recovery of albumin other filtered proteins escape glomerular filtration barrier. Studies our lab have shown knockout (KO) Lrp2 opossum PT cells leads to dramatic reduction sodium–glucose co-transporter 2 (SGLT2) transcript protein levels, as well differential expression genes involved mitochondrial metabolic function. SGLT2 levels are reduced more modestly KO mice. Here, we investigated effects on function health mice fed regular chow (RC) or Western-style diet (WD) high fat refined sugar. Despite modest expression, either showed increased glucose tolerance compared control Moreover, were protected against WD-induced gain. Surprisingly, renal male WD was compromised, exhibited significant injury with WD. Female less susceptible than KO. Together, findings reveal both positive negative contributions megalin health, highlight megalin-mediated sex-dependent response following

Language: Английский

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Dynamic changes of gut microbiota composition during the intervention of apple polyphenols extract to alleviate high-carbohydrate-diet induced body weight gain

Food Bioscience, Journal Year: 2024, Volume and Issue: 60, P. 104272 - 104272

Published: May 10, 2024

Language: Английский

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Fructose catabolism and its metabolic effects: Exploring host–microbiota interactions and the impact of ethnicity

The Journal of Physiology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 13, 2025

Important health disparities are observed in the prevalence of obesity and associated non-communicable diseases (NCDs), including type 2 diabetes (T2D) metabolic dysfunction-associated steatotic liver disease (MASLD) among ethnic groups. Yet, underlying factors accounting for these remain poorly understood. Fructose has been widely proposed as a potential mediator NCDs, given that hepatic fructose catabolism can result deleterious effects, insulin resistance steatosis. Moreover, fermentation by gut microbiota produce metabolites such ethanol acetate, both which serve substrates de novo lipogenesis (DNL) could therefore contribute to development conditions. Significant inter-ethnic differences composition have observed. consumption varies across groups, intake demonstrated significantly alter composition, influence its fermenting properties effects. Therefore, may be influenced variations consumption, disparities. This review provides an overview complex interactions between host microbial catabolism, role ethnicity shaping processes their impact on health. Understanding provide insights into mechanisms driving improve personalized nutrition strategies. KEY POINTS: Dietary increased substantially over recent decades, with rising (NCDs) disease. Pronounced different groups NCD dietary underscore need elucidate Together well-known toxic effects emerging evidence highlights small intestinal sugars like various bacterial products There significant that, combined varying mediate To comprehensively understand mediating fructose-induced adverse future research should focus microbiota. Future - account habits mentioned

Language: Английский

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