Current and Potential Therapies Targeting Inflammation in NASH

Albhaisi, Somaya; Noureddin, Mazen

doi:10.3389/fendo.2021.767314

Cited by 28 publications

(27 citation statements)

References 81 publications

(145 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This accumulation is lipotoxic, as the cells, already incapable of sequestering more reactive lipid molecules, have their mitochondrial beta-oxidation enzymatic system overloaded and suffer mitochondrial damage, endoplasmic reticulum (ER) stress, and autophagy. The results of obesity associated with NASH lead to hypertrophy of adipocytes, cell degeneration and death [ 2 , 6 , 23 , 24 ].…”

Section: Insulin Resistance the Role Of Fructose Gut Microbiota And Organokinesmentioning

confidence: 99%

“…This complex series of events ultimately culminates in the activation of HSCs, followed by excessive synthesis and extracellular matrix deposition. Thus, the loss of function of adipocytes added to adipose inflammation (presence of IL-1, IL-6, and TNF-α) contributes to the development of adipose resistance to insulin [ 10 , 23 , 28 , 29 ].…”

Section: Insulin Resistance the Role Of Fructose Gut Microbiota And Organokinesmentioning

confidence: 99%

See 1 more Smart Citation

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

Santos

Maio

Lemes

et al. 2022

IJMS

View full text Add to dashboard Cite

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

show abstract

Section: Insulin Resistance the Role Of Fructose Gut Microbiota And Organokinesmentioning

confidence: 99%

Section: Insulin Resistance the Role Of Fructose Gut Microbiota And Organokinesmentioning

confidence: 99%

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

Santos

Maio

Lemes

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…This condition can lead to nonalcoholic steatohepatitis (NASH), characterized by steatosis, inflammation, and liver damage, with or without fibrosis, which can progress to cirrhosis (requiring liver transplantation), hepatocellular carcinoma, and death. Hepatic inflammatory status appears to be the key factor in the progression from NAFLD to NASH [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Obese Vegetarians and Omnivores Show Different Metabolic Changes: Analysis of 1340 Individuals

et al. 2022

View full text Add to dashboard Cite

Our study evaluated the association between the increase in body mass index (BMI) in men and women (menstruating and non-menstruating) (n = 1340) with different dietary groups (omnivores, semi-vegetarians, lacto-ovo-vegetarian, and vegans) and the measurement of the biochemical markers high-sensitive C-reactive protein (hs-CRP), ferritin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), glycated hemoglobin (HbA1C), and insulin resistance index (HOMA-IR). Increasing BMI values in all groups and dietary profiles were related to a significant increase in hs-CRP (p < 0.0001), ALT (p = 0.02), ferritin (p = 0.009), and HbA1C (p < 0.0001), with no difference between dietary groups (p < 0.05). The increase in BMI increases the levels of HOMA-IR (p < 0.0001) and GGT (p < 0.05), with higher values found in men when compared to women (p < 0.0001 for HOMA- IR and p = 0.0048 for GGT). The association between ALT and BMI was different between dietary groups, as it showed a decrease in vegan women who do not menstruate compared to other dietary groups (p = 0.0099). When including only obese individuals (BMI = 30 kg/m2, n = 153) in the analysis, we observed lower concentrations of GGT and ferritin in vegetarians than in omnivores, regardless of gender and menstrual blood loss (p = 0.0395). Our data showed that for both vegetarians and omnivores, the higher the BMI, the worse the metabolic parameters. However, regarding obesity, vegetarians showed better antioxidant status (lower GGT elevation) and lower inflammatory status (lower ferritin elevation), which may provide them with potential protection in the development of morbidities associated with overweight.

show abstract

“…Therapeutic strategies in NASH target different aspects of NASH progression, from initial cellular stress to inflammation to fibrosis 8 . NASH is a manifestation of lipid overload due to increased fatty acid influx and insulin resistance in adipose tissues 19 .…”

Section: Targeted Therapeutic Strategies In Nashmentioning

confidence: 99%

“…Interventions for NAFLD involve addressing excess adiposity and its downstream inflammatory and fibrotic processes 7,8 , with the goal to prevent the progression of fibrosis and the development of adverse liver-related outcomes 9,10 . Since NAFLD is increasingly recognized as a hepatic manifestation of the metabolic syndrome 11 , comorbid diseases such as hypertension, hyperlipidemia, diabetes and obesity also need to be addressed to reduce major adverse cardiac events 12 .…”

Section: Introductionmentioning

confidence: 99%

Nonalcoholic Steatohepatitis Drug Development Pipeline: An Update

Chew

Truong

et al. 2022

Semin Liver Dis

Self Cite

View full text Add to dashboard Cite

Non-alcoholic steatohepatitis (NASH) is a burgeoning global health crisis that mirrors the obesity pandemic. This global health crisis has stimulated active research to develop novel NASH pharmacotherapies targeting dysregulated inflammatory, cellular stress and fibrogenetic processes that include: 1) metabolic pathways to improve insulin sensitivity, de-novo lipogenesis, and mitochondrial utilization of fatty acids, 2) cellular injury or inflammatory targets that reduce inflammatory cell recruitment and signalling, 3) liver-gut axis targets that influence bile acid enterohepatic circulation and signalling, and 4) anti-fibrotic targets. In this review, we summarize several of the therapeutic agents that have been studied in phase 2 and 3 randomized trials. In addition to reviewing novel therapeutic drugs targeting nuclear receptor pathways, liver chemokine receptors, liver lipid metabolism, lipotoxicity or cell death, and glucagon-like peptide-1 receptors, we also discuss the rationale behind the use of combination therapy and the lessons learned from unsuccessful or negative clinical trials.

show abstract

Current and Potential Therapies Targeting Inflammation in NASH

Cited by 28 publications

References 81 publications

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

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

Obese Vegetarians and Omnivores Show Different Metabolic Changes: Analysis of 1340 Individuals

Nonalcoholic Steatohepatitis Drug Development Pipeline: An Update

Contact Info

Product

Resources

About