Inflammation in obesity, diabetes, and related disorders

Immunity, Год журнала: 2022, Номер 55(1), С. 31 - 55

Опубликована: Янв. 1, 2022

Язык: Английский

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Dietary Fructose and Fructose-Induced Pathologies

Annual Review of Nutrition, Год журнала: 2022, Номер 42(1), С. 45 - 66

Опубликована: Авг. 22, 2022

The consumption of fructose as sugar and high-fructose corn syrup has markedly increased during the past several decades. This trend coincides with exponential rise metabolic diseases, including obesity, nonalcoholic fatty liver disease, cardiovascular diabetes. While biochemical pathways metabolism were elucidated in early 1990s, organismal-level its whole-body pathophysiological impacts have been only recently investigated. In this review, we discuss history consumption, molecular involved different organs gut microbiota, role pathogenesis remaining questions to treat such diseases.

Язык: Английский

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Pharmacologic inhibition of lipogenesis for the treatment of NAFLD

Journal of Hepatology, Год журнала: 2023, Номер 80(2), С. 362 - 377

Опубликована: Ноя. 15, 2023

Язык: Английский

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Nutritional Strategies for Battling Obesity-Linked Liver Disease: the Role of Medical Nutritional Therapy in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Management

Current Obesity Reports, Год журнала: 2025, Номер 14(1)

Опубликована: Янв. 11, 2025

This narrative review explores the role of Medical Nutritional Therapy (MNT) in managing Metabolic-Associated Steatotic Liver Disease (MASLD), previously known as nonalcoholic fatty liver disease. It aims to examine effectiveness specific nutritional strategies preventing and treating this obesity-linked Emerging evidence underscores benefits Mediterranean diet, low-carbohydrate diets, intermittent fasting reducing fat, improving insulin sensitivity, mitigating inflammation. Supplementing with vitamin E, omega-3 acids, silymarin can potentially reduce fibrosis promote health. MNT is a key intervention for MASLD management, emphasizing dietary patterns, caloric restriction, nutraceutical supplementation. Integrating these lifestyle modifications, including regular physical activity, offers comprehensive approach metabolic outcomes patients MASLD. Further research needed refine personalize therapeutic interventions.

Язык: Английский

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Integrative Metabolism in MASLD and MASH: Pathophysiology and Emerging Mechanisms

Journal of Hepatology, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

The liver acts as a central metabolic hub, integrating signals from the gastrointestinal tract and adipose tissue to regulate carbohydrate, lipid, amino acid metabolism. Gut-derived metabolites, such acetate ethanol non-esterified fatty acids white (WAT), influence hepatic processes, which rely on mitochondrial function maintain systemic energy balance. Metabolic dysregulation obesity, insulin resistance, type 2 diabetes disrupt these pathways, leading dysfunction-associated steatotic disease (MASLD) steatohepatitis (MASH). This review explores fluxes within gut-adipose tissue-liver axis, focusing pivotal role of de novo lipogenesis (DNL), dietary substrates like glucose fructose, changes in during MASLD progression. It highlights contributions resistance impaired dynamics lipid accumulation. Further understanding how interplay between substrate flux gastro-intestinal integrates with intersects structural functional alterations mitochondria will be important identify novel therapeutic targets advance treatment MASH.

Язык: Английский

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Short-Chain Fatty Acids Ameliorate Depressive-like Behaviors of High Fructose-Fed Mice by Rescuing Hippocampal Neurogenesis Decline and Blood–Brain Barrier Damage

Nutrients, Год журнала: 2022, Номер 14(9), С. 1882 - 1882

Опубликована: Апрель 29, 2022

Excessive fructose intake is associated with the increased risk of mental illness, such as depression, but underlying mechanisms are poorly understood. Our previous study found that high diet (FruD)-fed mice exhibited neuroinflammation, hippocampal neurogenesis decline and blood-brain barrier (BBB) damage, accompanied by reduction gut microbiome-derived short-chain fatty acids (SCFAs). Here, we chronic stress aggravated these pathological changes promoted development depressive-like behaviors in FruD mice. In detail, decreased number newborn neurons, mature neurons neural stem cells (NSCs) hippocampus was worsened stress. Furthermore, exacerbated damage BBB integrity expression zonula occludens-1 (ZO-1), claudin-5 occludin brain vasculature, overactivated microglia neuroinflammation These results suggest combined leads to cumulative negative effects promote Of note, SCFAs could rescue decline, improve suppress activation thereby ameliorate exposed be used develop dietary interventions prevent depression.

Язык: Английский

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Nonalcoholic steatohepatitis and mechanisms by which it is ameliorated by activation of the CNC-bZIP transcription factor Nrf2

Free Radical Biology and Medicine, Год журнала: 2022, Номер 188, С. 221 - 261

Опубликована: Июнь 18, 2022

Non-alcoholic steatohepatitis (NASH) represents a global health concern. It is characterised by fatty liver, hepatocyte cell death and inflammation, which are associated with lipotoxicity, endoplasmic reticulum (ER) stress, mitochondrial dysfunction, iron overload oxidative stress. NF-E2 p45-related factor 2 (Nrf2) transcription that combats Remarkably, Nrf2 downregulated during the development of NASH, probably accelerates disease, whereas in pre-clinical studies upregulation inhibits NASH. We now review scientific literature proposes downregulation NASH involves its increased ubiquitylation proteasomal degradation, mediated Kelch-like ECH-associated protein 1 (Keap1) and/or β-transducin repeat-containing (β-TrCP) HMG-CoA reductase degradation (Hrd1, also called synoviolin (SYVN1)). Additionally, Nrf2-mediated may involve diminished recruitment coactivators Nrf2, due to levels activating 3 (ATF3) nuclear factor-kappaB (NF-κB) p65, or competition for promoter binding BTB CNC homology (Bach1). Many processes downregulate triggered transforming growth factor-beta (TGF-β), stress amplifying signalling. Oxidative increase suppression β-TrCP through facilitating formation DSGIS-containing phosphodegron glycogen synthase kinase-3. In animal models, knockout increases susceptibility while pharmacological activation inducing agents target Keap1 These counter affected β-TrCP, Hrd1/SYVN1, ATF3, NF-κB p65 Bach1, suppressing Activation likely inhibit ameliorating ER overload. Crucially, mice has already been established supresses liver steatosis inflammation. There therefore compelling evidence provides comprehensive multipronged strategy treat

Язык: Английский

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The Good, the Bad and the New about Uric Acid in Cancer

Cancers, Год журнала: 2022, Номер 14(19), С. 4959 - 4959

Опубликована: Окт. 10, 2022

Uric acid is the final product of purine catabolism in man and apes. The serum concentration uric sex-, age- diet-dependent maintained close to its maximal solubility, indicating that it plays some important role. Indeed, has been demonstrated that, at physiological concentrations, a powerful antioxidant, while high intracellular pro-oxidant molecule. In this review, we describe possible causes accumulation or depletion metabolic regulatory pathways may impact. Particular attention given fructose, which, because complex correlation between carbohydrate nucleotide metabolism, accumulation. We also present recent results on positive negative effects played by cancer new findings hypotheses about implication metabolite variety signaling pathways, which can play role pathogenesis diseases such as syndrome, diabetes, inflammation, thus favoring development cancer. loss uricase Homo sapiens great apes, although exposing these species potentially adverse acid, appears be associated with evolutionary advantages.

Язык: Английский

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Diet-induced gut dysbiosis and inflammation: Key drivers of obesity-driven NASH

iScience, Год журнала: 2022, Номер 26(1), С. 105905 - 105905

Опубликована: Дек. 30, 2022

Sucrose, the primary circulating sugar in plants, contains equal amounts of fructose and glucose. The latter is predominant animals thus fuel source for various tissue cell types body. Chronic excessive energy intake has, however, emerged as a major driver obesity associated pathologies including nonalcoholic fatty liver diseases (NAFLD) more severe steatohepatitis (NASH). Consumption high-caloric, western-style diet induces gut dysbiosis inflammation resulting leaky gut. Translocation gut-derived bacterial content promotes hepatic ER stress, when either or both these are combined with steatosis, it can cause NASH. Here, we review metabolic links between diet-induced changes Furthermore, therapeutic interventions treatment also discussed focus on restoring gut-liver axis.

Язык: Английский

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NAT10/ac4C/FOXP1 Promotes Malignant Progression and Facilitates Immunosuppression by Reprogramming Glycolytic Metabolism in Cervical Cancer

Advanced Science, Год журнала: 2023, Номер 10(32)

Опубликована: Окт. 11, 2023

Immunotherapy has recently emerged as the predominant therapeutic approach for cervical cancer (CCa), driven by groundbreaking clinical achievements of immune checkpoint inhibitors (ICIs), such anti-PD-1/PD-L1 antibodies. N4-acetylcytidine (ac4C) modification, catalyzed NAT10, is an important posttranscriptional modification mRNA in cancers. However, its impact on immunological dysregulation and tumor immunotherapy response CCa remains enigmatic. Here, a significant increase NAT10 expression tissues initially observed that clinically associated with poor prognosis. Subsequently, it found HOXC8 activated binding to promoter, thereby stimulating ac4C FOXP1 enhancing translation efficiency, eventually leading induction GLUT4 KHK expression. Moreover, NAT10/ac4C/FOXP1 axis activity resulted increased glycolysis continuous lactic acid secretion cells. The acid-enriched microenvironment (TME) further contributed amplifying immunosuppressive properties tumor-infiltrating regulatory T cells (Tregs). Impressively, knockdown enhanced efficacy PD-L1 blockade-mediated regression vivo. Taken together, findings revealed oncogenic role initiating crosstalk between cell immunosuppression, which can be target synergistic PD-1/PD-L1 blockade CCa.

Язык: Английский

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