Autophagy alterations in obesity, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease: the evidence from human studies DOI Creative Commons

Patrycja Jakubek,

B. Pakuła,

Martin Rossmeisl

et al.

Internal and Emergency Medicine, Journal Year: 2024, Volume and Issue: 19(5), P. 1473 - 1491

Published: July 6, 2024

Abstract Autophagy is an evolutionarily conserved process that plays a pivotal role in the maintenance of cellular homeostasis and its impairment has been implicated pathogenesis various metabolic diseases including obesity, type 2 diabetes (T2D), dysfunction-associated steatotic liver disease (MASLD). This review synthesizes current evidence from human studies on autophagy alterations under these conditions. In most data point to upregulation during initiation phase autophagosome formation, potentially response proinflammatory conditions adipose tissue. Autophagosome formation appears be enhanced hyperglycemic or insulin-resistant patients with T2D, possibly acting as compensatory mechanism eliminate damaged organelles proteins. Other have proposed prolonged hyperglycemia disrupted insulin signaling hinder autophagic flux, resulting accumulation dysfunctional components can contribute β-cell dysfunction. Evidence MASLD supports inhibition progression. Nevertheless, given available data, it difficult ascertain whether suppressed because levels markers depend overall metabolism specific organs, tissues, experimental conditions, duration. Owing constraints, determining observed shifts activity precede result remains challenging. Additionally, autophagy-modulating strategies are shortly discussed. To conclude, more investigating required gain comprehensive understanding unveil novel therapeutic for

Language: Английский

EASL–EASD–EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD) DOI Creative Commons
Frank Tacke, Paul Horn, Vincent Wai‐Sun Wong

et al.

Journal of Hepatology, Journal Year: 2024, Volume and Issue: 81(3), P. 492 - 542

Published: June 7, 2024

Language: Английский

Citations

361
Effects of dietary intervention on human diseases: molecular mechanisms and therapeutic potential DOI Creative Commons

Yu-Ling Xiao,

Yue Gong,

Ying-Jia Qi

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: March 11, 2024

Abstract Diet, serving as a vital source of nutrients, exerts profound influence on human health and disease progression. Recently, dietary interventions have emerged promising adjunctive treatment strategies not only for cancer but also neurodegenerative diseases, autoimmune cardiovascular metabolic disorders. These demonstrated substantial potential in modulating metabolism, trajectory, therapeutic responses. Metabolic reprogramming is hallmark malignant progression, deeper understanding this phenomenon tumors its effects immune regulation significant challenge that impedes eradication. Dietary intake, key environmental factor, can tumor metabolism. Emerging evidence indicates might affect the nutrient availability tumors, thereby increasing efficacy treatments. However, intricate interplay between pathogenesis other diseases complex. Despite encouraging results, mechanisms underlying diet-based remain largely unexplored, often resulting underutilization management. In review, we aim to illuminate various interventions, including calorie restriction, fasting-mimicking diet, ketogenic protein restriction high-salt high-fat high-fiber aforementioned diseases. We explore multifaceted impacts these encompassing their immunomodulatory effects, biological impacts, molecular mechanisms. This review offers valuable insights into application therapies

Language: Английский

Citations

69
EASL-EASD-EASO Clinical Practice Guidelines on the Management of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) DOI Creative Commons
Frank Tacke, Paul Horn, Vincent Wai‐Sun Wong

et al.

Obesity Facts, Journal Year: 2024, Volume and Issue: 17(4), P. 374 - 444

Published: Jan. 1, 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed non-alcoholic fatty (NAFLD), is defined as (SLD) in the presence of one or more cardiometabolic risk factor(s) and absence harmful alcohol intake. The spectrum MASLD includes steatosis, metabolic steatohepatitis (MASH, NASH), fibrosis, cirrhosis MASH-related hepatocellular carcinoma (HCC). This joint EASL-EASD-EASO guideline provides an update on definitions, prevention, screening, diagnosis treatment for MASLD. Case-finding strategies with using non-invasive tests, should be applied individuals factors, abnormal enzymes, and/or radiological signs hepatic particularly type 2 diabetes (T2D) obesity additional factor(s). A stepwise approach blood-based scores (such FIB-4) and, sequentially, imaging techniques transient elastography) suitable to rule-out/in advanced which predictive liver-related outcomes. In adults MASLD, lifestyle modification - including weight loss, dietary changes, physical exercise discouraging consumption well optimal management comorbidities use incretin-based therapies (e.g. semaglutide, tirzepatide) T2D obesity, if indicated advised. Bariatric surgery also option obesity. If locally approved dependent label, non-cirrhotic MASH significant fibrosis (stage ≥2) considered a MASH-targeted resmetirom, demonstrated histological effectiveness acceptable safety tolerability profile. No pharmacotherapy can currently recommended cirrhotic stage. Management adaptations drugs, nutritional counselling, surveillance portal hypertension HCC, transplantation decompensated cirrhosis.

Language: Английский

Citations

65
Treating NASH by targeting peroxisome proliferator-activated receptors DOI Creative Commons
Bart Staels, Laura Butruille, Sven Francque

et al.

Journal of Hepatology, Journal Year: 2023, Volume and Issue: 79(5), P. 1302 - 1316

Published: July 17, 2023

Language: Английский

Citations

48
Epidemiology, screening, and co-management of type 2 diabetes mellitus and metabolic dysfunction–associated steatotic liver disease DOI Creative Commons
Xiaolong Qi, Jie Li, Cyrielle Caussy

et al.

Hepatology, Journal Year: 2024, Volume and Issue: unknown

Published: May 8, 2024

Metabolic dysfunction–associated steatotic liver disease (MASLD), previously known as NAFLD, is increasingly recognized a prevalent global burden. Type 2 diabetes mellitus (T2DM), another important metabolic disease, considered major contributor to the development of MASLD. MASLD and T2DM have strong association with each other due shared pathogenic mechanisms. The co-existence diseases increases risk liver-related adverse outcomes imposes heavier burden on extrahepatic outcomes, representing substantial public health issue. Effective assessment management combined necessitate multidisciplinary approach. emergence numerous RCTs has shed light treatment This review uncovers epidemiology intertwined MASLD, offers insights into evaluation hepatic fibrosis in patients T2DM, glucose monitoring population, provides comprehensive co-management strategies for addressing both diseases.

Language: Английский

Citations

21
Exercise-induced adipokine Nrg4 alleviates MASLD by disrupting hepatic cGAS-STING signaling DOI Creative Commons
Min Chen, Yang Li,

Jieying Zhu

et al.

Cell Reports, Journal Year: 2025, Volume and Issue: 44(2), P. 115251 - 115251

Published: Jan. 31, 2025

Language: Английский

Citations

2
Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in Children with Obesity: An Obesity Medicine Association (OMA) and Expert Joint Perspective 2025 DOI Creative Commons

Jennifer Panganiban,

Mohit Kehar, Samar H. Ibrahim

et al.

Obesity Pillars, Journal Year: 2025, Volume and Issue: 14, P. 100164 - 100164

Published: Feb. 1, 2025

This Obesity Medicine Association (OMA) Expert Joint Perspective examines steatotic liver disease (SLD), which is composed of metabolic dysfunction-associated (MASLD), and steatohepatitis (MASH) in children with obesity. The prevalence obesity increasing, rates have tripled since 1963 from 5 % to now 19 US affected 2018. MASLD, the most common seen children, can be a precursor development Type 2 Diabetes (T2DM) primary reason for transplant listing young adults. We must vigilant prevention treatment MASLD childhood prevent further progression. joint clinical perspective based upon scientific evidence, peer expertise. medical literature was reviewed via PubMed search appropriate articles were included this review. work formulated collaboration eight hepatologists/gastroenterologists expertise two physicians OMA. authors who are experts field, determined sentinel questions often asked by clinicians regarding They created consensus guideline on screening, diagnosis, associated children. comorbidity increasing problem that needs addressed urgently. It well known chronic continue these diseases as adults, leads reduced life expectancy, quality life, healthcare financial burden. paper recommend healthy weight reduction not only through lifestyle modification but pharmacotherapy bariatric surgery. Therefore, guidance reviews available therapies achieve reverse progressive fibrosis, disease.

Language: Английский

Citations

2
Intermittent fasting improves hepatic end points in nonalcoholic fatty liver disease: A systematic review and meta-analysis DOI Creative Commons
Marcia Lange,

Devika Nadkarni,

Lily Martin

et al.

Hepatology Communications, Journal Year: 2023, Volume and Issue: 7(8)

Published: Aug. 1, 2023

Background and Aims: Despite NAFLD being the most prevalent liver disease globally, currently there are no FDA-approved treatments, weight loss through caloric restriction enhanced physical activity is recommended treatment strategy. Intermittent fasting (IF) has been proposed as an alternative strategy with additional cardiometabolic benefits. In this systematic review meta-analysis, we evaluated anthropometric, biochemical, hepatic impacts of IF in patients NAFLD. Methods: MEDLINE, EMBASE, Cochrane Central, conference abstracts were searched for interventions adults until April 2, 2023. Meta-analysis a random effects model was used to compare pre-intervention post-intervention changes end points intervention group control group. Publication bias assessed using Egger’s test. Results: Fourteen studies included ten meta-analysis (n = 840 participants, 44.64% male). Studies varied modalities diagnosis, duration (4–52 weeks), type (5:2 diet, modern alternate-day fasting, time-restricted eating, or religious fasting). Body weight, body mass index, waist hip ratio all significantly improved following ( p < 0.05). Adults showed improvement serum alanine transaminase, aspartate aminotransferase, steatosis (controlled attenuation parameter measured by vibration-controlled transient elastography), stiffness (measured elastography) after Conclusions: There limited, but moderate- high-quality evidence suggest that can improve promote Larger randomized controlled extended needed further validate our findings.

Language: Английский

Citations

29
Cdo1-Camkk2-AMPK axis confers the protective effects of exercise against NAFLD in mice DOI Creative Commons
Min Chen,

Jieying Zhu,

Wang-Jing Mu

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Dec. 18, 2023

Exercise is an effective non-pharmacological strategy for ameliorating nonalcoholic fatty liver disease (NAFLD), but the underlying mechanism needs further investigation. Cysteine dioxygenase type 1 (Cdo1) a key enzyme cysteine catabolism that enriched in liver, whose role NAFLD remains poorly understood. Here, we show exercise induces expression of hepatic Cdo1 via cAMP/PKA/CREB signaling pathway. Hepatocyte-specific knockout (Cdo1LKO) decreases basal metabolic rate mice and impairs effect against NAFLD, whereas hepatocyte-specific overexpression (Cdo1LTG) increases synergizes with to ameliorate NAFLD. Mechanistically, tethers Camkk2 AMPK by interacting both them, thereby activating signaling. This promotes acid oxidation mitochondrial biogenesis hepatocytes attenuate hepatosteatosis. Therefore, promoting Camkk2-AMPK pathway, acts as important downstream effector combat

Language: Английский

Citations

28
Combined versus independent effects of exercise training and intermittent fasting on body composition and cardiometabolic health in adults: a systematic review and meta-analysis DOI Creative Commons
Mousa Khalafi, Michael Symonds, Aref Habibi Maleki

et al.

Nutrition Journal, Journal Year: 2024, Volume and Issue: 23(1)

Published: Jan. 6, 2024

Abstract Introduction and aim Exercise training (Ex) intermittent fasting (IF) are effective for improving body composition cardiometabolic health overweight obese adults, but whether combining Ex IF induces additive or synergistic effects is less well established. We therefore, performed a systematic review meta-analysis to compare the combined versus independent of on in adults. Method An electronic search was conducted three main online databases including PubMed, Web Science, Scopus, from inception March 9, 2023 studies involving plus trials standalone and/or interventions Interventions had duration ≥ 2 weeks. Standardized (SMD) weighted mean differences (WMD) 95% confidence intervals were calculated order weight, mass index (BMI), fat lean (LBM), visceral fat, waist circumference. For health, outcomes included glucose, insulin, total cholesterol (TC), low-density lipoprotein (LDL), triglycerides (TG), high-density (HDL), systolic (SBP) diastolic (DBP) blood pressure, VO max/peak. Results decreased weight [WMD: -3.03 kg (95% CI: -3.44 -2.61), p = 0.001], BMI -1.12 kg.m -1.28 -0.95), [SMD: -0.72 -1.23 -0.21), 0.005], -0.34 -0.63 -0.05), 0.01], circumference -2.63 cm -4.16 -1.11), 0.001] more than alone. However, changes markers not significantly different when compared with alone, exception max/peak 0.55 0.14 0.97), 0.009]. Conclusion demonstrate that combination produces superior composition, could therefore be loss has no other markers.

Language: Английский

Citations

15