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, Год журнала: 2024, Номер 121(20)

Опубликована: Май 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

Язык: 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, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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

Frontiers in Endocrinology, Год журнала: 2025, Номер 15

Опубликована: Янв. 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.

Язык: Английский

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Linoleic Acid, Mitochondria, Gut Microbiome, and Metabolic Health: A Mechanistic Review

Advances in Redox Research, Год журнала: 2025, Номер unknown, С. 100128 - 100128

Опубликована: Апрель 1, 2025

Язык: Английский

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

European Journal of Nutrition, Год журнала: 2023, Номер 62(8), С. 3113 - 3124

Опубликована: Авг. 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.

Язык: Английский

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

Nutrients, Год журнала: 2023, Номер 15(7), С. 1778 - 1778

Опубликована: Апрель 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.

Язык: Английский

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Gut microbiota in MAFLD: therapeutic and diagnostic implications

Therapeutic Advances in Endocrinology and Metabolism, Год журнала: 2024, Номер 15

Опубликована: Янв. 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.

Язык: Английский

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Mitochondria at the Crossroads: Linking the Mediterranean Diet to Metabolic Health and Non-Pharmacological Approaches to NAFLD

Nutrients, Год журнала: 2025, Номер 17(7), С. 1214 - 1214

Опубликована: Март 30, 2025

Nonalcoholic fatty liver disease (NAFLD) is a growing global health concern that closely linked to metabolic syndrome, yet no approved pharmacological treatment exists. The Mediterranean diet (MD) emerged as first-line dietary intervention for NAFLD, offering and hepatoprotective benefits. Now conceptualized complex chemical matrix rich in bioactive compounds, the MD exerts antioxidant anti-inflammatory effects, improving insulin sensitivity lipid metabolism. Mitochondria play central role NAFLD pathophysiology, influencing energy metabolism, oxidative stress, homeostasis. Emerging evidence suggests MD's compounds enhance mitochondrial function by modulating phosphorylation, biogenesis, mitophagy. However, most research has focused on individual rather than whole, leaving gaps understanding its collective impact pattern. This narrative review explores how influence highlighting key pathways such substrate control, dynamics, efficiency. A literature search was conducted identify relevant studies MD, mitochondria, NAFLD. While promising, our remains incomplete, particularly when current knowledge limited lack of mechanistic comprehensive holistic impact. Future integrating cutting-edge experimental approaches needed elucidate intricate diet-mitochondria interactions. deeper influences essential developing precision-targeted nutritional strategies can effectively prevent manage disease.

Язык: Английский

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

Nutrients, Год журнала: 2022, Номер 14(23), С. 4961 - 4961

Опубликована: Ноя. 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

Язык: Английский

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Different Effects of High-Fat/High-Sucrose and High-Fructose Diets on Advanced Glycation End-Product Accumulation and on Mitochondrial Involvement in Heart and Skeletal Muscle in Mice

Nutrients, Год журнала: 2023, Номер 15(23), С. 4874 - 4874

Опубликована: Ноя. 22, 2023

Diets with an elevated content of fat, sucrose, or fructose are recognized models diet-induced metabolic alterations, since they induce derangements, oxidative stress, and chronic low-grade inflammation associated local systemic accumulation advanced glycation end-products (AGEs). This study used four-week-old C57BL/6 male mice, randomly assigned to three experimental dietary regimens: standard diet (SD), high-fat high-sucrose (HFHS), high (HFr), administered for 12 weeks. Plasma, heart, tibialis anterior (TA) skeletal muscle were assayed markers conditions, inflammation, presence AGEs, mitochondrial involvement. The HFHS induced a tissue-specific differential response featuring (1) remarkable adaptation the heart HFHS-induced heavy demonstrated by increased AGEs reduced biogenesis, efficaciously counteracted conspicuous increase in fission PRXIII expression; (2) absence TA HFHS, revealed reduction not expression. HFr-induced mild stress elicited responses, decrease biogenesis likely tendency TA, fusion, showing adaptability both tissues diet.

Язык: Английский

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