Insights into the molecular targets and emerging pharmacotherapeutic interventions for nonalcoholic fatty liver disease

Negi, Chander K.; Babica, Pavel; Bajard, Lola; Bienertová-Vašků, Julie; Tarantino, Giovanni

doi:10.1016/j.metabol.2021.154925

Cited by 152 publications

(149 citation statements)

References 170 publications

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“…Targeting NAFLD with the aim to prevent disease progression may be an incremental component of patient management strategies. However, most of the recent phase 3 trials testing novel compounds have been prematurely terminated and as of now there is still no specific treatment approved for NAFLD [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

The Potential Role of Cellular Senescence in Non-Alcoholic Fatty Liver Disease

Engelmann

Tacke

2022

IJMS

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Non-alcoholic fatty liver disease (NAFLD) represents an increasing global health burden. Cellular senescence develops in response to cellular injury, leading not only to cell cycle arrest but also to alterations of the cellular phenotype and metabolic functions. In this review, we critically discuss the currently existing evidence for the involvement of cellular senescence in NAFLD in order to identify areas requiring further exploration. Hepatocyte senescence can be a central pathomechanism as it may foster intracellular fat accumulation, fibrosis and inflammation, also due to secretion of senescence-associated inflammatory mediators. However, in some non-parenchymal liver cell types, such as hepatic stellate cells, senescence may be beneficial by reducing the extracellular matrix deposition and thereby reducing fibrosis. Deciphering the detailed interaction between NAFLD and cellular senescence will be essential to discover novel therapeutic targets halting disease progression.

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Section: Introductionmentioning

confidence: 99%

The Potential Role of Cellular Senescence in Non-Alcoholic Fatty Liver Disease

Engelmann

Tacke

2022

IJMS

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“…It seems that improvement may occur but is still partial yet ultrasonographically undetected. This may need longer follow-up or introduction of a therapeutic agent as prescribed by Negi et al [ 28 ]. Many drugs are now on the pipeline trying to offer a solution for NAFLD.…”

Section: Discussionmentioning

confidence: 99%

Impact of Weight Reduction on Thyroid Function and Nonalcoholic Fatty Liver among Egyptian Adolescents with Obesity

Amin

Ali²,

El-Sayed

2022

International Journal of Endocrinology

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Background. The prevalence of childhood obesity has been increasing worldwide. This may explain the emergence of nonalcoholic fatty liver as the leading cause of liver disease. Several previous studies have addressed the association between thyroid function and nonalcoholic fatty liver disease. Objectives. To study the impact of weight reduction through lifestyle modifications in adolescents with obesity. Methods. A prospective cohort study was done on 61 adolescents with obesity. Patients were evaluated at the first visit by the full history, clinical examination, and investigations (thyroid profile, lipid profile, liver function tests, HbA1c, and liver ultrasonography) as basal information. The intervention program included a dietary program, increasing physical activity, and decreasing sedentary activity. A postintervention evaluation was done at the end of six months which included anthropometric measures, laboratory results, and ultrasonographic estimation. Results. It was shown that the mean BMI of the participants had significantly decreased after lifestyle modification from (32.05 ± 3.36 kg/m2) to (28.1 ± 2.77 kg/m2) ( P < 0.001 ). It also showed that the percentage of studied adolescents with elevated TSH decreased from 47.5% to 19.7% after the weight reduction program. Improvement was also achieved in the lipid profile and liver functions. The percentage of studied adolescents with ultrasound appearance of NAFLD decreased from 31.1% to 26.2% after weight reduction. Conclusions. Lifestyle modification positively influences the metabolic derangement in obesity without medical treatment. ΔTSH is a significant predictor of the change in BMI z-score. It is also possible that hepatic steatosis affects thyroid function rather than the other way around.

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“…The communication between the gut and liver is through the biliary tract, portal vein, and systemic circulation ( Tripathi et al, 2018 ). Currently, there is no approved drugs for the treatment of NAFLD, and several anti-NAFLD drugs are being undergoing various phases of recent clinical trials ( Negi et al, 2022 ). However, natural polysaccharides extracted from plants exhibit great potential in alleviating NAFLD through manipulation of gut microbiota.…”

Section: Hfd-induced Non-alcoholic Fatty Liver Diseasementioning

confidence: 99%

Targeting Gut Microbiota With Natural Polysaccharides: Effective Interventions Against High-Fat Diet-Induced Metabolic Diseases

et al. 2022

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Unhealthy diet, in particular high-fat diet (HFD) intake, can cause the development of several metabolic disorders, including obesity, hyperlipidemia, type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), and metabolic syndrome (MetS). These popular metabolic diseases reduce the quality of life, and induce premature death worldwide. Evidence is accumulating that the gut microbiota is inextricably associated with HFD-induced metabolic disorders, and dietary intervention of gut microbiota is an effective therapeutic strategy for these metabolic dysfunctions. Polysaccharides are polymeric carbohydrate macromolecules and sources of fermentable dietary fiber that exhibit biological activities in the prevention and treatment of HFD-induced metabolic diseases. Of note, natural polysaccharides are among the most potent modulators of the gut microbiota composition. However, the prebiotics-like effects of polysaccharides in treating HFD-induced metabolic diseases remain elusive. In this review, we introduce the critical role of gut microbiota human health and HFD-induced metabolic disorders. Importantly, we review current knowledge about the role of natural polysaccharides in improving HFD-induced metabolic diseases by regulating gut microbiota.

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Insights into the molecular targets and emerging pharmacotherapeutic interventions for nonalcoholic fatty liver disease

Cited by 152 publications

References 170 publications

The Potential Role of Cellular Senescence in Non-Alcoholic Fatty Liver Disease

The Potential Role of Cellular Senescence in Non-Alcoholic Fatty Liver Disease

Impact of Weight Reduction on Thyroid Function and Nonalcoholic Fatty Liver among Egyptian Adolescents with Obesity

Targeting Gut Microbiota With Natural Polysaccharides: Effective Interventions Against High-Fat Diet-Induced Metabolic Diseases

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