Liver fat as risk factor of hepatic and cardiometabolic diseases

Demir, Münevver; Bornstein, Stefan R.; Mantzoros, Christos S.; Perakakis, Nikolaos

doi:10.1111/obr.13612

Cited by 5 publications

(4 citation statements)

References 237 publications

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“…Currently, research on this disease is mainly conducted using mouse models. Hepatic lipid accumulation plays a pivotal role in the pathogenesis of NAFLD, contributing significantly to the development and progression of the disease [ 5 ]. Our experimental findings provide compelling evidence that PPE treatment effectively mitigated the excessive hepatic accumulation of TC, a hallmark of NAFLD, in the murine model.…”

Section: Discussionmentioning

confidence: 99%

“…This shift underscores the complexity of NAFLD, linking its onset to a network of molecular pathways within the body [ 4 ]. Central to these is the imbalance in cholesterol homeostasis, identified as a primary risk factor in NAFLD development [ 5 ]. Cholesterol homeostasis is a tightly regulated process, encompassing endogenous synthesis, exogenous uptake, efflux, and biotransformation.…”

Section: Introductionmentioning

confidence: 99%

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Therapeutic Role of Polyphenol Extract from Prunus cerasifera Ehrhart on Non-Alcoholic Fatty Liver

Ren,

Zhang,

Heiyan-Perhat

et al. 2024

Plants

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Prunus cerasifera Ehrhart (P. cerasifera) flourishes uniquely in the arid landscapes of Xinjiang, China. Preliminary studies have revealed the therapeutic potential of its polyphenol extract (PPE) in mitigating liver lipid accumulation in mice fed a high-fat diet. We established a mouse model that was subjected to a continuous high-fat diet for 24 weeks and administered PPE to investigate the effects of PPE on cholesterol and BA metabolism in NAFLD mice. The results showed that PPE administration (200 and 400 mg/kg/day, BW) led to a reduction in liver TC, an increase in liver T-BAs, and normalization of the disrupted fecal BA profile. Concurrently, it decreased levels of lipotoxic BAs and inhibited hepatic cholesterol synthesis (evidenced by reduced HMGCR activity) and intestinal cholesterol absorption (indicated by lower ACAT2 levels) while enhancing intestinal cholesterol efflux (via LXRα, ABCA1, ABCG5, and ABCG8) and stimulating hepatic BA synthesis (CYP7A1, CYP27A1) and secretion (BSEP). PPE thus led to a significant reduction in lipotoxic BAs metabolized by gut microbiota and a downregulation of the BA secretion pathway under its influence. Our findings reveal the therapeutic effect of PPE on NAFLD mice via regulating cholesterol and BA metabolism, providing a theoretical basis for exploring the potential functions of P. cerasifera.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Therapeutic Role of Polyphenol Extract from Prunus cerasifera Ehrhart on Non-Alcoholic Fatty Liver

Ren,

Zhang,

Heiyan-Perhat

et al. 2024

Plants

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“…2 Moreover, the risk of NAFLD in people with T2D is closely related to chronic kidney disease (CKD), with a higher prevalence of NAFLD in patients with CKD compared with those without. 3 NAFLD is also associated with an increased incidence and risk of progression of CKD 4 and may be linked to an increased risk of cardiovascular disease (CVD), [5][6][7][8] despite current therapies. 9,10 Finerenone, a selective, nonsteroidal mineralocorticoid receptor (MR) antagonist (MRA) that inhibits MR overactivation, [11][12][13][14][15][16] was recently approved to slow the progression of CKD and reduce the risk of CV events in adults with CKD associated with T2D.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of finerenone in patients with type 2 diabetes, chronic kidney disease and altered markers of liver steatosis and fibrosis: A FIDELITY subgroup analysis

Perakakis,

Bornstein,

Birkenfeld

et al. 2023

Diabetes Obesity Metabolism

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AimInvestigating the effect of finerenone on liver function, cardiovascular and kidney composite outcomes in patients with chronic kidney disease and type 2 diabetes, stratified by their risk of liver steatosis, inflammation and fibrosis.Materials and MethodsPost hoc analysis stratified patients (N = 13 026) by liver fibrosis and enzymes: high risk of steatosis (hepatic steatosis index >36); elevated transaminases [alanine transaminase (ALT) >33 (males) and >25 IU/L (females)]; and fibrosis‐4 (FIB‐4) index scores >3.25, >2.67 and >1.30. Liver enzymes were assessed by changes in ALT, aspartate aminotransferase and gamma‐glutamyl transferase. Composite kidney outcome was defined as onset of kidney failure, sustained estimated glomerular filtration rate decline ≥57% from baseline over ≥4 weeks or kidney death. Composite cardiovascular outcome was defined as cardiovascular death, non‐fatal myocardial infarction, non‐fatal stroke or hospitalization for heart failure.ResultsALT, aspartate aminotransferase and gamma‐glutamyl transferase levels were consistent between treatment groups and remained stable throughout. Finerenone consistently reduced the risk of composite kidney outcome, irrespective of altered liver tests. Higher FIB‐4 score was associated with higher incidence rates of composite cardiovascular outcome. Finerenone reduced the risk of composite cardiovascular outcome versus placebo in FIB‐4 subgroups by 52% (>3.25), 39% (>2.67) and 24% (>1.30) (p values for interaction = .01, .13 and .03, respectively).ConclusionsFinerenone has neutral effects on liver parameters in patients with chronic kidney disease and type 2 diabetes. Finerenone showed robust and consistent kidney benefits in patients with altered liver tests, and profound cardiovascular benefits even in patients with higher FIB‐4 scores who were at high risk of developing cardiovascular complications.

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“…NAFLD is characterized by an accumulation of fat in the liver, and is strongly associated with insulin resistance and metabolic syndrome features [ 14 , 15 , 16 , 17 , 18 ]. In particular, NAFLD is considered the hepatic manifestation of the metabolic syndrome and a novel independent risk factor for cardiovascular disease [ 19 , 20 , 21 , 22 ]. NAFLD may progress to non-alcoholic steatohepatitis (NASH), cirrhosis and, eventually, hepatocarcinoma [ 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

Prevalence of Non-Alcoholic Fatty Liver Disease in Adult Individuals with Moderate-to-Severe Atopic Dermatitis

Maurelli,

Gisondi,

Bellinato

et al. 2023

JCM

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Background: There are no published studies on the prevalence of non-alcoholic fatty liver disease (NAFLD) in patients with atopic dermatitis (AD). Objectives: To estimate the prevalence of NAFLD (assessed via liver ultrasonography) in adults with moderate-to-severe AD. Methods: We performed a retrospective, cross-sectional, observational study including adult patients affected by moderate-to-severe AD, moderate-to-severe chronic plaque psoriasis, or a previous diagnosis of thin melanoma in situ (considered as the control group) who attended the Verona University Hospital between January 2022 and April 2023. Fatty liver was assessed via liver ultrasonography. Results: A total of 144 adults with AD, 466 with chronic plaque psoriasis, and 99 with thin melanoma were included. The prevalence rates of ultrasound-detected NAFLD among patients with in situ melanoma, those with moderate-to-severe AD, and those with moderate-to-severe chronic plaque psoriasis were 23.2% (23 out of 99), 24.1% (36 out of 144), and 49.8% (228 out of 466), respectively (p < 0.01). Logistic regression analysis revealed that being of male sex, a higher age, a higher body mass index, and psoriasis were independently associated with NAFLD, whereas AD was not. Conclusions: Our findings show that the prevalence of ultrasound-detected NAFLD in patients with moderate-to-severe AD was comparable to that of patients with a previous diagnosis of in situ melanoma. It is plausible to hypothesize that the Th2-type inflammation typically characterizing AD is not a risk factor for NAFLD. Patients with moderate-to-severe psoriasis, but not those with AD, should be screened for NAFLD and other metabolic comorbidities.

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Liver fat as risk factor of hepatic and cardiometabolic diseases

Cited by 5 publications

References 237 publications

Therapeutic Role of Polyphenol Extract from Prunus cerasifera Ehrhart on Non-Alcoholic Fatty Liver

Therapeutic Role of Polyphenol Extract from Prunus cerasifera Ehrhart on Non-Alcoholic Fatty Liver

Efficacy of finerenone in patients with type 2 diabetes, chronic kidney disease and altered markers of liver steatosis and fibrosis: A FIDELITY subgroup analysis

Prevalence of Non-Alcoholic Fatty Liver Disease in Adult Individuals with Moderate-to-Severe Atopic Dermatitis

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