Non-alcoholic fatty liver disease development: A multifactorial pathogenic phenomena

Bashir, Aamir; Duseja, Ajay; De, Arka; Mehta, Manu; Tiwari, Pramil

doi:10.1016/j.livres.2022.05.002

Cited by 14 publications

(5 citation statements)

References 127 publications

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“…In continuation of our previous studies [ 40 , 45 , 74 ] on the most bioactive compound of S. macrophylla seeds, swietenine, we have investigated the activity of swietenine in diabetes-induced NAFLD. Although our studies have shown promising bioactivity, there are limitations in the study design (because of time and financial constraints): (1) NAFLD is a multifactorial disease [ 75 ], and there is no single physiologically relevant animal model [ 76 ]. Thus, future studies must be carried out to confirm the bioactivity of swietenine in other animal models.…”

Section: Discussionmentioning

confidence: 99%

Swietenine Alleviates Nonalcoholic Fatty Liver Disease in Diabetic Mice via Lipogenesis Inhibition and Antioxidant Mechanisms

et al. 2023

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Our previous studies have reported the effect of swietenine (a major bioactive component of Swietenia macrophylla seeds) in reversing and potentiating the effect of metformin in hyperglycemia and hyperlipidaemia in diabetic rats. Moreover, we reported that the anti-inflammatory effect of swietenine is mediated via the activation of nuclear factor erythroid 2-related factor 2 (Nrf2). This study evaluated the effect of swietenine and its mechanisms in nonalcoholic fatty liver disease (NAFLD) in high-fat diet/streptozotocin-induced diabetic mice. The effect was assessed by determining blood biochemical parameters (glucose, cholesterol, triglycerides, alanine transaminase (ALT), asparate transaminase (AST), alkaline phosphatase (ALP), glutathione (GSH), total antioxidant capacity (TAC), and malondialdehyde (MDA)) and liver biochemical parameters (liver index, cholesterol, and triglycerides). Hepatic lipid accumulation (initial causative factor in NAFLD) was determined by oil-O-red staining. Gene expression (qPCR) and immunohistochemical studies were performed to elucidate the mechanism of swietenine’s effect in NAFLD. The critical regulators (genes and proteins) involved in lipogenesis (ACLY, ACC1, FASN, SREBP1c, and ChREBPβ) and oxidative stress (Nrf2, NQO-1 and HO-1) pathways were determined. In mice fed with a high-fat diet followed by streptozotocin injection, the liver cholesterol, triglycerides, and lipids were elevated. These increases were reversed by the oral administration of swietenine, 80 mg/kg body weight, on alternate days for eight weeks. Gene expression and immunohistochemical studies showed that swietenine reversed the elevated levels of crucial enzymes of lipogenesis (ACLY, ACC1 and FASN) and their master transcription factors (SREBP1c and ChREBPβ). Furthermore, swietenine activated the Nrf2 antioxidant defense mechanism, as evidenced by the upregulated levels of Nrf2, NQO-1, and HO-1. It is concluded that swietenine shows beneficial effects in diabetes-induced NAFLD via inhibiting lipogenesis and activating the Nrf2 pathway.

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Section: Discussionmentioning

confidence: 99%

Swietenine Alleviates Nonalcoholic Fatty Liver Disease in Diabetic Mice via Lipogenesis Inhibition and Antioxidant Mechanisms

et al. 2023

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“…However, the elucidation of the mechanisms involved in the development of fatty liver is still ongoing. Insulin resistance (IR), proinflammatory stimuli, oxidative imbalance, alterations in the gut microbiota, vitamin D deficiency, and thyroid dysfunction are thought to contribute to lipid deposition in hepatocytes [69]. VDR may have an indirect effect on the development of NAFLD, as it is involved in some of these factors.…”

Section: Indirect Effects Of Vdr On the Development Of Nafldmentioning

confidence: 99%

“…There are several reversible cycles between the NAFL and NASH stages before cirrhosis occurs. Around 10-20% of these cycles rapidly progress to fibrosis, and 80-90% and 10-20% of NASH patients show slow and rapid progression to cirrhosis and HCC, respectively [69].…”

Section: The Role Of Vitamin D-vdr Signaling In Nafld Disease Progres...mentioning

confidence: 99%

Gene Polymorphisms and Biological Effects of Vitamin D Receptor on Nonalcoholic Fatty Liver Disease Development and Progression

Tourkochristou

Mouzaki

Triantos

2023

IJMS

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Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, with increasing prevalence worldwide. The genetic and molecular background of NAFLD pathogenesis is not yet clear. The vitamin D/vitamin D receptor (VDR) axis is significantly associated with the development and progression of NAFLD. Gene polymorphisms may influence the regulation of the VDR gene, although their biological significance remains to be elucidated. VDR gene polymorphisms are associated with the presence and severity of NAFLD, as they may influence the regulation of adipose tissue activity, fibrosis, and hepatocellular carcinoma (HCC) development. Vitamin D binds to the hepatic VDR to exert its biological functions, either by activating VDR transcriptional activity to regulate gene expression associated with inflammation and fibrosis or by inducing intracellular signal transduction through VDR-mediated activation of Ca2+ channels. VDR activity has protective and detrimental effects on hepatic steatosis, a characteristic feature of NAFLD. Vitamin D-VDR signaling may control the progression of NAFLD by regulating immune responses, lipotoxicity, and fibrogenesis. Elucidation of the genetic and molecular background of VDR in the pathophysiology of NAFLD will provide new therapeutic targets for this disease through the development of VDR agonists, which already showed promising results in vivo.

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“…En la actualidad se reconoce una hipótesis multifactorial, en la que la resistencia a la insulina (IR) sería uno de los principales gatillantes. Contribuyen a su desarrollo la predisposición genética, la dieta, el sedentarismo y la disbiosis intestinal, factores que en conjunto promueven un estado elevado de estrés oxidativo y una aumentada activación de la respuesta inmune a nivel hepático y sistémico (6) .…”

Section: Introductionunclassified

El estrés psicosocial en la esteatosis hepática asociada a disfunción metabólica (MASLD): sobreposición desfavorable

Aleman F.,

Dufeu G.,

Fuenzalida R.

et al. 2024

Rev. Hosp. Clín. Univ. Chile (En línea)

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The metabolic dysfunction-associated steatotic liver disease (MASLD)(1) is considered the leading cause of liver disease worldwide. It is a complex pathology, which includes a spectrum of diseases ranging from steatosis to advanced forms of liver damage, such as cirrhosis. Its prevalence has increased in recent years, becoming a relevant public health problem. It is characterized by fat accumulation in hepatocytes, which induces lipotoxicity, oxidative stress, inflammation, and consequently, liver damage. The mechanisms involved in MASLD progression are not fully understood. Also, the factors that determine the heterogeneous susceptibility towards liver fibrosis among patients, remain unresolved. In recent years, chronic stress has been described as a relevant risk factor in the progression of MASLD. The presence of stress is associated with alterations in the gut-liver-brain axis, which promotes systemic low-grade inflammation that reinforces the liver damage progression. This review aims to discuss the evidence about the role of psychosocial stress in MASLD and its association with the pathogenic mechanisms involved in liver damage.

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Non-alcoholic fatty liver disease development: A multifactorial pathogenic phenomena

Cited by 14 publications

References 127 publications

Swietenine Alleviates Nonalcoholic Fatty Liver Disease in Diabetic Mice via Lipogenesis Inhibition and Antioxidant Mechanisms

Swietenine Alleviates Nonalcoholic Fatty Liver Disease in Diabetic Mice via Lipogenesis Inhibition and Antioxidant Mechanisms

Gene Polymorphisms and Biological Effects of Vitamin D Receptor on Nonalcoholic Fatty Liver Disease Development and Progression

El estrés psicosocial en la esteatosis hepática asociada a disfunción metabólica (MASLD): sobreposición desfavorable

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