Insulin Resistance across the Spectrum of Nonalcoholic Fatty Liver Disease

Armandi, Angelo; Rosso, Chiara; Caviglia, Gian Paolo; Bugianesi, Elisabetta

doi:10.3390/metabo11030155

Cited by 64 publications

(54 citation statements)

References 115 publications

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“…Insulin is a potent anabolic hormone that after ingestion is synthesized in pancreatic β-cells of the Langerhans islets as pre-proinsulin (a single chain); subsequently, its signal peptide is removed in the endoplasmic reticulum to generate proinsulin, which has three domains (amino-terminal B chain, a carboxy-terminal A chain, and a connecting peptide (CP) in the middle). Within the endoplasmic reticulum, proinsulin is processed by specific endopeptidases that cleave the CP, thus generating the mature form of insulin [ 19 , 22 ]. Insulin induces its actions by binding to the insulin receptor, which activates receptor autophosphorylation and subsequently triggers a downstream signaling cascade through the phosphorylation of tyrosine residues of the IRS-1 or IRS-2, followed by phosphorylation of phosphatidylinositol 3-kinase (PI3K), Akt1 and Akt2, PKC, and the mammalian target of rapamycin (mTOR), including ribosomal protein S6 kinase beta 1 (S6K1).…”

Section: Insulin Hormonementioning

confidence: 99%

“…Progressive adipose tissue dysfunction and insulin resistance are key processes in NASH development and in hepatic fibrosis progression, supporting the existence of an adipose-tissue-liver crosstalk [ 19 , 20 ]. Several studies have associated NASH with atherosclerosis, increased coronary artery score, arterial stiffening, endothelial dysfunction, and myocardial dysfunction.…”

Section: Introductionmentioning

confidence: 99%

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Pathophysiological Molecular Mechanisms of Obesity: A Link between MAFLD and NASH with Cardiovascular Diseases

Gutiérrez–Cuevas

Santos

Armendáriz‐Borunda

2021

IJMS

125

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Obesity is now a worldwide epidemic ensuing an increase in comorbidities’ prevalence, such as insulin resistance, type 2 diabetes (T2D), metabolic dysfunction-associated fatty liver disease (MAFLD), nonalcoholic steatohepatitis (NASH), hypertension, cardiovascular disease (CVD), autoimmune diseases, and some cancers, CVD being one of the main causes of death in the world. Several studies provide evidence for an association between MAFLD and atherosclerosis and cardio-metabolic disorders, including CVDs such as coronary heart disease and stroke. Therefore, the combination of MAFLD/NASH is associated with vascular risk and CVD progression, but the underlying mechanisms linking MAFLD/NASH and CVD are still under investigation. Several underlying mechanisms may probably be involved, including hepatic/systemic insulin resistance, atherogenic dyslipidemia, hypertension, as well as pro-atherogenic, pro-coagulant, and pro-inflammatory mediators released from the steatotic/inflamed liver. MAFLD is strongly associated with insulin resistance, which is involved in its pathogenesis and progression to NASH. Insulin resistance is a major cardiovascular risk factor in subjects without diabetes. However, T2D has been considered the most common link between MAFLD/NASH and CVD. This review summarizes the evidence linking obesity with MAFLD, NASH, and CVD, considering the pathophysiological molecular mechanisms involved in these diseases. We also discuss the association of MAFLD and NASH with the development and progression of CVD, including structural and functional cardiac alterations, and pharmacological strategies to treat MAFLD/NASH and cardiovascular prevention.

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Section: Insulin Hormonementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pathophysiological Molecular Mechanisms of Obesity: A Link between MAFLD and NASH with Cardiovascular Diseases

Gutiérrez–Cuevas

Santos

Armendáriz‐Borunda

2021

IJMS

125

View full text Add to dashboard Cite

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“…Hepatitis C virus itself decreases insulin sensitivity by altering insulin signaling and increasing endoplasmic reticulum stress [ 46 , 47 , 48 ]. Hepatic and systemic insulin resistance often precedes the onset of cirrhosis and is present in individuals with NAFLD [ 49 , 50 ].…”

Section: Endocrine Manifestations Of Hepatic Diseasementioning

confidence: 99%

Hepatocrinology

2021

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Hepatocrinology is defined as a bidirectional, complex relationship between hepatic physiology and endocrine function, hepatic disease and endocrine dysfunction, hepatotropic drugs and endocrine function, and endocrine drugs and hepatic health. The scope of hepatocrinology includes conditions of varied etiology (metabolic, infectious, autoimmune, and invasive) that we term as hepato-endocrine syndromes. This perspective shares the definition, concept, and scope of hepatocrinology and shares insight related to this aspect of medicine. It is hoped that this communication will encourage further attention and research in this critical field.

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“…Several mechanisms that explain the close connection between CVD and NAFLD have been suggested. It is known that IR plays a crucial role in NAFLD and NASH pathogenesis [28]. In addition, IR affects many physiological processes and causes hyperglycemia and dyslipidemia, activating low-grade chronic inflammation, ectopic lipid accumulation, OS (oxidative stress), and endothelial dysfunction [29].…”

Section: Association Between Liver and Heart Diseasementioning

confidence: 99%

Mitochondrial Lipid Homeostasis at the Crossroads of Liver and Heart Diseases

Dabravolski

Bezsonov

Baig

et al. 2021

IJMS

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The prevalence of NAFLD (non-alcoholic fatty liver disease) is a rapidly increasing problem, affecting a huge population around the globe. However, CVDs (cardiovascular diseases) are the most common cause of mortality in NAFLD patients. Atherogenic dyslipidemia, characterized by plasma hypertriglyceridemia, increased small dense LDL (low-density lipoprotein) particles, and decreased HDL-C (high-density lipoprotein cholesterol) levels, is often observed in NAFLD patients. In this review, we summarize recent genetic evidence, proving the diverse nature of metabolic pathways involved in NAFLD pathogenesis. Analysis of available genetic data suggests that the altered operation of fatty-acid β-oxidation in liver mitochondria is the key process, connecting NAFLD-mediated dyslipidemia and elevated CVD risk. In addition, we discuss several NAFLD-associated genes with documented anti-atherosclerotic or cardioprotective effects, and current pharmaceutical strategies focused on both NAFLD treatment and reduction of CVD risk.

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Insulin Resistance across the Spectrum of Nonalcoholic Fatty Liver Disease

Cited by 64 publications

References 115 publications

Pathophysiological Molecular Mechanisms of Obesity: A Link between MAFLD and NASH with Cardiovascular Diseases

Pathophysiological Molecular Mechanisms of Obesity: A Link between MAFLD and NASH with Cardiovascular Diseases

Hepatocrinology

Mitochondrial Lipid Homeostasis at the Crossroads of Liver and Heart Diseases

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