Expanding the phenotypic spectrum of non-alcoholic fatty liver disease and hypertriglyceridemia DOI Creative Commons
Marica Meroni, Miriam Longo, Erika Paolini

et al.

Frontiers in Nutrition, Journal Year: 2022, Volume and Issue: 9

Published: Sept. 15, 2022

Hypertriglyceridemia is a common feature of metabolic syndrome (MetS), as well non-alcoholic fatty liver disease (NAFLD), which considered the hepatic manifestation MetS. Fat accumulation in hepatocytes may alter mitochondrial homeostasis predisposing to advanced disease. Here, we report case 40-year-old woman with early aggressive NAFLD due severe hypertriglyceridemia that ensued from combination genetic variants and additional risk factors. Genetic screening was performed by using whole-exome sequencing (WES), structures were evaluated TEM. At presentation, patient reported have hepatomegaly, hypertriglyceridemia, raised transaminases. analysis revealed beard heritable alterations genes implicated lipid handling, among APOB, APOE, CETP, HSPG2, accompanied missense mutations involved function, i.e., AK2, ALG6, ASPA, NDUFAF1, POLG, TMEM70. Abdominal ultrasound (US) transient elastography suggestive steatosis fibrosis. A biopsy confirmed diagnosis steatohepatitis (NASH)-related Thus, better outline whether remodeling function also affect organelles' morphology, exploited Along multifaceted abnormalities architecture been already observed patients NAFLD, astonishing ultrastructural defects, such vacuolization, sub-compartmentalization, onion-like mitochondria, identified. The anomalies expand phenotypic spectrum contribute switching toward progressive

Language: Английский

New insights into the role of mitochondrial dynamics in oxidative stress-induced diseases DOI Open Access
Sisi Chen, Qilong Li,

Hanjing Shi

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 178, P. 117084 - 117084

Published: Aug. 1, 2024

The accumulation of excess reactive oxygen species (ROS) can lead to oxidative stress (OS), which induce gene mutations, protein denaturation, and lipid peroxidation directly or indirectly. expression is reduced ATP level in cells, increased cytoplasmic Ca

Language: Английский

Citations

42
Epidemiologic, Genetic, Pathogenic, Metabolic, Epigenetic Aspects Involved in NASH-HCC: Current Therapeutic Strategies DOI Open Access
Jorge Gutiérrez‐Cuevas, Silvia Lucano‐Landeros, Daniel López-Cifuentes

et al.

Cancers, Journal Year: 2022, Volume and Issue: 15(1), P. 23 - 23

Published: Dec. 20, 2022

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and sixth frequent in world, being third cause of cancer-related deaths. Nonalcoholic steatohepatitis (NASH) characterized by fatty infiltration, oxidative stress necroinflammation liver, with or without fibrosis, which can progress to advanced cirrhosis HCC. Obesity, metabolic syndrome, insulin resistance, diabetes exacerbates course NASH, elevate risk The growing prevalence obesity are related increasing incidence may play a role HCC epidemiology worldwide. In addition, initiation progression driven reprogramming metabolism, indicates appreciation metabolism pathogenesis this disease. Although no specific preventive pharmacological treatments have recommended for dietary restriction exercise recommended. This review focuses on molecular connections between including genetic factors, highlighting aberrant epigenetic alterations development NASH. Current therapeutic aspects NASH/HCC also reviewed.

Language: Английский

Citations

39
Tumor Mutational Burden for Predicting Prognosis and Therapy Outcome of Hepatocellular Carcinoma DOI Open Access
Daniela Gabbia, Sara De Martin

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 3441 - 3441

Published: Feb. 8, 2023

Hepatocellular carcinoma (HCC), the primary hepatic malignancy, represents second-highest cause of cancer-related death worldwide. Many efforts have been devoted to finding novel biomarkers for predicting both patients' survival and outcome pharmacological treatments, with a particular focus on immunotherapy. In this regard, recent studies focused unravelling role tumor mutational burden (TMB), i.e., total number mutations per coding area genome, ascertain whether it can be considered reliable biomarker used either stratification HCC patients in subgroups different responsiveness immunotherapy, or prediction disease progression, particularly relation etiologies. review, we summarize advances study TMB TMB-related landscape, focusing their feasibility as guides therapy decisions and/or predictors clinical outcome.

Language: Английский

Citations

23
The Saga of Endocrine FGFs DOI Creative Commons
Phuc Phan,

Bibhuti Ballav Saikia,

Shivakumar Sonnaila

et al.

Cells, Journal Year: 2021, Volume and Issue: 10(9), P. 2418 - 2418

Published: Sept. 14, 2021

Fibroblast growth factors (FGFs) are cell-signaling proteins with diverse functions in cell development, repair, and metabolism. The human FGF family consists of 22 structurally related members, which can be classified into three separate groups based on their action mechanisms, namely: intracrine, paracrine/autocrine, endocrine subfamilies. FGF19, FGF21, FGF23 belong to the hormone-like/endocrine subfamily. These FGFs mainly associated regulation metabolic activities such as homeostasis lipids, glucose, energy, bile acids, minerals (phosphate/active vitamin D). Endocrine function through a unique protein called klotho. Two members this family, α-klotho, or β-klotho, act main cofactors scaffold tether FGF19/21/23 receptor(s) (FGFRs) form an active complex. There ongoing studies pertaining structure mechanism these individual ternary complexes. aim provide potential insights physiological pathophysiological roles therapeutic strategies for diseases. Herein, we comprehensive review history, structure–function relationship(s), downstream signaling, roles, future perspectives FGFs.

Language: Английский

Citations

45
Mitochondrial Mechanisms of Apoptosis and Necroptosis in Liver Diseases DOI Creative Commons

Qingfei Chu,

Xinyu Gu, Qiuxian Zheng

et al.

Analytical Cellular Pathology, Journal Year: 2021, Volume and Issue: 2021, P. 1 - 9

Published: Nov. 11, 2021

In addition to playing a pivotal role in cellular energetics and biosynthesis, mitochondrial components are key operators the regulation of cell death. apoptosis, necrosis is highly relevant form programmed liver Differential activation specific forms death may not only affect outcome disease but also provide new opportunities for therapeutic intervention. This review describes mitochondria mechanism that leads chronic hepatitis cirrhosis. We focus on mitochondrial-driven apoptosis current knowledge necroptosis discuss strategies targeting mitochondrial-mediated diseases.

Language: Английский

Citations

41
Non-Alcoholic Steatohepatitis (NASH) and Organokines: What Is Now and What Will Be in the Future DOI Open Access

João Paulo Margiotti dos Santos,

Mariana Canevari de Maio,

Monike Alves Lemes

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(1), P. 498 - 498

Published: Jan. 2, 2022

Non-alcoholic steatohepatitis (NASH) is characterized by steatosis, lobular inflammation, and enlargement of the diameter hepatocytes (ballooning hepatocytes), with or without fibrosis. It affects 20% patients non-alcoholic fatty liver disease (NAFLD). Due to dysfunction numerous metabolic changes that commonly accompany condition (obesity, insulin resistance, type 2 diabetes, syndrome), secretion organokines modified, which may contribute pathogenesis progression disease. In this sense, study aimed perform a review role in NASH. Thus, combining descriptors such as NASH, organokines, oxidative stress, dyslipidemia, search was carried out EMBASE, MEDLINE-PubMed, Cochrane databases articles published last ten years. Insulin inflammation mitochondrial dysfunction, fructose, intestinal microbiota were factors identified participating genesis Changes pattern (adipokines, myokines, hepatokines, osteokines) directly indirectly aggravating compromise homeostasis. further studies involving skeletal muscle, adipose, bone, tissue endocrine organs are essential better understand modulation involved NASH advance treatment

Language: Английский

Citations

38
mTOR-dependent loss of PON1 secretion and antiphospholipid autoantibody production underlie autoimmunity-mediated cirrhosis in transaldolase deficiency DOI Creative Commons

Thomas Winans,

Zachary Oaks,

G. Choudhary

et al.

Journal of Autoimmunity, Journal Year: 2023, Volume and Issue: 140, P. 103112 - 103112

Published: Sept. 22, 2023

Language: Английский

Citations

21
Mitochondrial Dysfunction in Metabolic Dysfunction Fatty Liver Disease (MAFLD) DOI Open Access

Ying Zhao,

Yanni Zhou, Dan Wang

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(24), P. 17514 - 17514

Published: Dec. 15, 2023

Nonalcoholic fatty liver disease (NAFLD) has become an increasingly common in Western countries and the major cause of cirrhosis or hepatocellular carcinoma (HCC) addition to viral hepatitis recent decades. Furthermore, studies have shown that NAFLD is inextricably linked development extrahepatic diseases. However, there currently no effective treatment cure NAFLD. In addition, 2020, was renamed metabolic dysfunction (MAFLD) show its pathogenesis closely related disorders. Recent reported MAFLD associated with mitochondrial hepatocytes hepatic stellate cells (HSCs). Simultaneously, stress caused by structural functional disorders stimulates occurrence accumulation fat lipo-toxicity HSCs. interaction between liver-gut axis also a new point during MAFLD. this review, we summarize effects several potential strategies for MAFLD, including antioxidants, reagents, intestinal microorganisms metabolites.

Language: Английский

Citations

21
Glutamine prevents high-fat diet-induced hepatic lipid accumulation in mice by modulating lipolysis and oxidative stress DOI Creative Commons
Yongjie Zhang,

Yangli Wang,

Xin Liao

et al.

Nutrition & Metabolism, Journal Year: 2024, Volume and Issue: 21(1)

Published: March 8, 2024

Abstract Metabolic-associated fatty liver disease (MAFLD) is related to metabolic dysfunction and characterized by excess fat storage in the liver. Several studies have indicated that glutamine could be closely associated with lipid metabolism disturbances because of its important role intermediary metabolism. However, effect supplementation on MAFLD progression remains unclear. Here, we used a high-fat diet (HFD)-induced C57BL/6 mouse model, was supplied drinking water at different time points for prevention reversal studies. A study performed feeding mice an HFD concomitant 4% treatment 24 weeks, whereas based 13 weeks after 10 weeks. In study, ameliorated serum storage, hepatic injury, oxidative stress HFD-induced obese mice, although did not affect body weight, glucose homeostasis, energy expenditure, mitochondrial function. there were no noticeable changes basic physiological phenotype summary, might prevent, but reverse, suggesting cautious attitude required regarding use treatment.

Language: Английский

Citations

7
Recent Advances in miRNA-Based Therapy for MASLD/MASH and MASH-Associated HCC DOI Open Access
Sara Carpi, Simona Daniele,

Jacqueline Almeida

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 12229 - 12229

Published: Nov. 14, 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty (NAFLD), is a growing health concern worldwide, affecting more than 1 billion adults. It may progress to metabolic steatohepatitis (MASH), cirrhosis, and ultimately hepatocellular carcinoma (HCC). Emerging evidence has demonstrated the role in this transition of microRNAs (miRNAs), which regulate expression genes associated with lipid metabolism, inflammation, fibrosis, cell proliferation. Specific miRNAs have been identified exacerbate or mitigate fibrotic carcinogenic processes hepatic cells. The modulation these through synthetic mimics inhibitors represents promising therapeutic strategy. Preclinical models that miRNA-based therapies can attenuate reduce inhibit tumorigenesis, thus delaying preventing onset HCC. However, challenges such delivery mechanisms, off-target effects, long-term safety remain be addressed. This review, focusing on recently published preclinical clinical studies, explores pharmacological potential interventions prevent MASLD/MASH progression toward

Language: Английский

Citations

7