The Leu72Met (rs696217 G&gt;T) Polymorphism of the Ghrelin Gene Might Be a Protective Factor for Nonalcoholic Fatty Liver Disease

Tabaeian, Seidamir Pasha; Mahmoudi, Touraj; Sabzikarian, Mohammad; Rezamand, Gholamreza; Dabiri, Reza; Nobakht, Hossein; Asadi, Asadollah; Farahani, Hamid; Mansour-Ghanaei, Fariborz; Zali, Mohammad Reza

doi:10.15403/jgld-2703

Cited by 8 publications

(4 citation statements)

References 52 publications

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“…Moreover, it was demonstrated that ghrelin exerts an impact on insulin resistance and inflammation, both of which play crucial roles in the development of MASLD [265][266][267][268]. In this context, the rs26802/rs696217 variants in the ghrelin gene have been observed to have a preventive effect against MASLD progression in genetic investigations [269,270]. Ghrelin exists in two distinct forms inside the bloodstream: acylated ghrelin (AG) and unacylated ghrelin (UAG) [268].…”

Section: Ghrelinmentioning

confidence: 99%

Role of Perturbated Hemostasis in MASLD and Its Correlation with Adipokines

Pezzino,

Luca,

Castorina

et al. 2024

Life

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The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) continues to rise, making it one of the most prevalent chronic liver disorders. MASLD encompasses a range of liver pathologies, from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH) with inflammation, hepatocyte damage, and fibrosis. Interestingly, the liver exhibits close intercommunication with fatty tissue. In fact, adipose tissue could contribute to the etiology and advancement of MASLD, acting as an endocrine organ that releases several hormones and cytokines, with the adipokines assuming a pivotal role. The levels of adipokines in the blood are altered in people with MASLD, and recent research has shed light on the crucial role played by adipokines in regulating energy expenditure, inflammation, and fibrosis in MASLD. However, MASLD disease is a multifaceted condition that affects various aspects of health beyond liver function, including its impact on hemostasis. The alterations in coagulation mechanisms and endothelial and platelet functions may play a role in the increased vulnerability and severity of MASLD. Therefore, more attention is being given to imbalanced adipokines as causative agents in causing disturbances in hemostasis in MASLD. Metabolic inflammation and hepatic injury are fundamental components of MASLD, and the interrelation between these biological components and the hemostasis pathway is delineated by reciprocal influences, as well as the induction of alterations. Adipokines have the potential to serve as the shared elements within this complex interrelationship. The objective of this review is to thoroughly examine the existing scientific knowledge on the impairment of hemostasis in MASLD and its connection with adipokines, with the aim of enhancing our comprehension of the disease.

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Section: Ghrelinmentioning

confidence: 99%

Role of Perturbated Hemostasis in MASLD and Its Correlation with Adipokines

Pezzino,

Luca,

Castorina

et al. 2024

Life

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“…Additionally, higher levels of AG, but not UAG, were observed in higher stages of fibrosis [ 78 ]. Further evidencing the role of ghrelin in NAFLD, recent case-control retrospective studies of biopsy-proven NAFLD patients suggested that the Leu72Met (rs696217 G > T) polymorphism and the “GG” genotype of rs26802 variant in the ghrelin gene have a protective effect against NAFLD [ 79 , 80 ].…”

Section: Adipokines In Nafld: Evidence From Clinical Studiesmentioning

confidence: 99%

Adipokines in Non-Alcoholic Fatty Liver Disease: Are We on the Road toward New Biomarkers and Therapeutic Targets?

Francisco

Sanz

Real

et al. 2022

Biology

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Non-alcoholic fatty liver disease (NAFLD) has become the major cause of chronic hepatic illness and the leading indication for liver transplantation in the future decades. NAFLD is also commonly associated with other high-incident non-communicable diseases, such as cardiovascular complications, type 2 diabetes, and chronic kidney disease. Aggravating the socio-economic impact of this complex pathology, routinely feasible diagnostic methodologies and effective drugs for NAFLD management are unavailable. The pathophysiology of NAFLD, recently defined as metabolic associated fatty liver disease (MAFLD), is correlated with abnormal adipose tissue–liver axis communication because obesity-associated white adipose tissue (WAT) inflammation and metabolic dysfunction prompt hepatic insulin resistance (IR), lipid accumulation (steatosis), non-alcoholic steatohepatitis (NASH), and fibrosis. Accumulating evidence links adipokines, cytokine-like hormones secreted by adipose tissue that have immunometabolic activity, with NAFLD pathogenesis and progression; however, much uncertainty still exists. Here, the current knowledge on the roles of leptin, adiponectin, ghrelin, resistin, retinol-binding protein 4 (RBP4), visfatin, chemerin, and adipocyte fatty-acid-binding protein (AFABP) in NAFLD, taken from preclinical to clinical studies, is overviewed. The effect of therapeutic interventions on adipokines’ circulating levels are also covered. Finally, future directions to address the potential of adipokines as therapeutic targets and disease biomarkers for NAFLD are discussed.

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“…NAFLD patients are more predisposed to have insulin resistance (IR), type 2 diabetes (T2D), and obesity. IR also affects the rate of elevation of serum liver enzymes in NAFLD, and the rate is higher in NAFLD patients with IR than those without IR 1 - 3 . Interestingly, significant associations between insulin receptor ( INSR ), insulin-like growth factor 1 ( IGF1 ), insulin-like growth factor-binding protein 3 ( IGFBP3 ), and visfatin ( NAMPT ) gene polymorphisms, and the risk of NAFLD have been discovered 4 - 7 .…”

Section: Introductionmentioning

confidence: 99%

NAMPT gene rs2058539 variant is a risk factor for nonalcoholic fatty liver disease

Nouri,

Navari,

Zarei

et al. 2024

Rev. Assoc. Med. Bras.

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SUMMARY OBJECTIVE: Nonalcoholic fatty liver disease is a chronic liver disease and a growing global epidemic. The aim of this study was to investigate the association between a visfatin gene ( NAMPT ) variant and nonalcoholic fatty liver disease, owing to the connection between this disease and insulin resistance, obesity, inflammation, and oxidative stress, and the role of visfatin in these metabolic disorders. METHODS: In the present case-control study, we enrolled 312 genetically unrelated individuals, including 154 patients with biopsy-proven nonalcoholic fatty liver disease and 158 controls. The rs2058539 polymorphism of NAMPT gene was genotyped using the PCR-RFLP method. RESULTS: Genotype and allele distributions of NAMPT gene rs2058539 polymorphism conformed to the Hardy-Weinberg equilibrium both in the case and control groups (p>0.05). The distribution of NAMPT rs2058539 genotypes and alleles differed significantly between the cases with nonalcoholic fatty liver disease and controls. The "CC" genotype of the NAMPT rs2058539 compared with "AA" genotype was associated with a 2.5-fold increased risk of nonalcoholic fatty liver disease after adjustment for confounding factors [p=0.034; odds ratio (OR)=2.52, 95% confidence interval (CI)=1.36–4.37]. Moreover, the NAMPT rs2058539 "C" allele was significantly overrepresented in the nonalcoholic fatty liver disease patients than controls (p=0.022; OR=1.77, 95%CI=1.14–2.31). CONCLUSION: Our findings indicated for the first time that the NAMPT rs2058539 "CC" genotype is a marker of increased nonalcoholic fatty liver disease susceptibility; however, it needs to be supported by further investigations in other populations.

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The Leu72Met (rs696217 G>T) Polymorphism of the Ghrelin Gene Might Be a Protective Factor for Nonalcoholic Fatty Liver Disease

Cited by 8 publications

References 52 publications

Role of Perturbated Hemostasis in MASLD and Its Correlation with Adipokines

Role of Perturbated Hemostasis in MASLD and Its Correlation with Adipokines

Adipokines in Non-Alcoholic Fatty Liver Disease: Are We on the Road toward New Biomarkers and Therapeutic Targets?

NAMPT gene rs2058539 variant is a risk factor for nonalcoholic fatty liver disease

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