The Vicious Circle of Hepatic Glucagon Resistance in Non-Alcoholic Fatty Liver Disease

Galsgaard, Katrine D.

doi:10.3390/jcm9124049

Cited by 26 publications

(26 citation statements)

References 115 publications

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“…During the investigation of laboratory profiles in our cohort, we observed many instances of blood parameters' departure from normality, where both COVID and non-COVID patients with cirrhosis showed abnormal values such as preexistent anemia, hypoglycemia, elevated liver enzymes, poor liver function tests, nutritional deficiency, kidney failure, and hypolipidemia. Similar findings were separately described in different studies until present day, such as anemia in cirrhosis [16], hypoglycemia in cirrhosis [17], or hypolipidemia suffered by patients with cirrhosis [18]. However, all these studies did not describe their findings in conjunction with the presence of SARS-CoV-2.…”

Section: Discussionsupporting

confidence: 69%

Laboratory Profile of COVID-19 Patients with Hepatitis C-Related Liver Cirrhosis

Cerbu

Grigoraş

Bratosin

et al. 2022

JCM

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Patients with cirrhosis are known to have multiple comorbidities and impaired organ system functioning due to alterations caused by chronic liver failure. In the past two years, since the COVID-19 pandemic started, several studies have described the affinity of SARS-CoV-2 with the liver and biliary cells. Considering hepatitis C as a significant independent factor for cirrhosis in Romania, this research was built on the premises that this certain group of patients is susceptible to alterations of their serum parameters that are yet to be described, which might be useful in the management of COVID-19 in these individuals. A retrospective cohort study was developed at a tertiary hospital for infectious disease in Romania, which included a total of 242 patients with hepatitis C cirrhosis across two years, out of which 46 patients were infected with SARS-CoV-2. Stratification by patient weight and COVID-19 status identified several important laboratory serum tests as predictors for acute-on-chronic liver failure and risk for intensive care unit admission. Thus, white blood cell count, lymphocyte count, ferritin, hypoglycemia, prothrombin time, and HCV viral load were independent risk factors for ACLF in patients with COVID-19. High PT, creatinine, BUN, and HCV viral load were the strongest predictors for ICU admission. Inflammatory markers and parameters of gas exchange were also observed as risk factors for ACLF and ICU admission, including procalcitonin, CRP, IL-6, and D-dimers. Our study questions and confirms the health impact of COVID-19 on patients with cirrhosis and whether their laboratory profile significantly changes due to SARS-CoV-2 infection.

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Section: Discussionsupporting

confidence: 69%

Laboratory Profile of COVID-19 Patients with Hepatitis C-Related Liver Cirrhosis

Cerbu

Grigoraş

Bratosin

et al. 2022

JCM

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“…4 An important question underlining this work concerns the biological relevance of glucagon fibril-induced catalysis. Indeed, our observations that glucagon fibrils catalyze key hydrolysis reactions might shed light on pathological conditions such as fatty liver 66,67 and other lipid metabolism disorders 6,68,69 in which phospholipids and triglycerides, together with their derivatives, accumulate in the liver and interfere with the normal lipid metabolism. In diabetes, for example, free fatty acids (FFAs), possible byproducts of glucagon-fibril induced lipid hydrolysis, affect impaired uptake of glucose in muscle and liver, giving rise to insulin resistance.…”

Section: Resultsmentioning

confidence: 98%

Native Glucagon Amyloids Catalyze Key Metabolic Reactions

et al. 2022

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Glucagon is a prominent peptide hormone, playing central roles in the regulation of glucose blood-level and lipid metabolism. Formation of glucagon amyloid fibrils has been previously reported, although no biological functions of such fibrils are known. Here, we demonstrate that glucagon amyloid fibrils catalyze biologically important reactions, including esterolysis, lipid hydrolysis, and dephosphorylation. In particular, we found that glucagon fibrils catalyze dephosphorylation of adenosine triphosphate (ATP), a core metabolic reaction in cell biology. Comparative analysis of several glucagon variants allowed mapping the catalytic activity to an enzymatic pocket-like triad formed at the glucagon fibril surface, comprising the histidyl-serine domain at the N-terminus of the peptide. This study may point to previously unknown physiological roles and pathological consequences of glucagon fibrillation and supports the hypothesis that catalytic activities of native amyloid fibrils play functional roles in human physiology and disease.

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“…Mitochondrial membrane damage, hepatocyte apoptosis, inflammatory infiltration, and necrosis are altogether expressions of a pathological continuum occurring in the state of NAFLD/NASH, where the main intracellular actor is the mitochondrion. Furthermore, mitochondria dysfunction is a consequence of all these events, in the context of a vicious circle that overloads the normal activity of the remaining mitochondria [ 23 ]. Some evidence shows that oxidative stress is one of the main drivers of hepatocyte damage and contributes actively to the pathological progression from SFL to steatohepatitis [ 10 ].…”

Section: Non-alcoholic Fatty Liver Disease Pathophysiologymentioning

confidence: 99%

Dietary Polyphenols and Non-Alcoholic Fatty Liver Disease

et al. 2021

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Non-alcoholic fatty liver disease (NAFLD), which is emerging as a major public health issue worldwide, is characterized by a wide spectrum of liver disorders, ranging from simple fat accumulation in hepatocytes, also known as steatosis, to non-alcoholic steatohepatitis (NASH) and cirrhosis. At present, the pharmacological treatment of NAFLD is still debated and dietary strategies for the prevention and the treatment of this condition are strongly considered. Polyphenols are a group of plant-derived compounds whose anti-inflammatory and antioxidant properties are associated with a low prevalence of metabolic diseases, including obesity, hypertension, and insulin resistance. Since inflammation and oxidative stress are the main risk factors involved in the pathogenesis of NAFLD, recent studies suggest that the consumption of polyphenol-rich diets is involved in the prevention and treatment of NAFLD. However, few clinical trials are available on human subjects with NAFLD. Here, we reviewed the emerging existing evidence on the potential use of polyphenols to treat NAFLD. After introducing the physiopathology of NAFLD, we focused on the most investigated phenolic compounds in the setting of NAFLD and described their potential benefits, starting from basic science studies to animal models and human trials.

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The Vicious Circle of Hepatic Glucagon Resistance in Non-Alcoholic Fatty Liver Disease

Cited by 26 publications

References 115 publications

Laboratory Profile of COVID-19 Patients with Hepatitis C-Related Liver Cirrhosis

Laboratory Profile of COVID-19 Patients with Hepatitis C-Related Liver Cirrhosis

Native Glucagon Amyloids Catalyze Key Metabolic Reactions

Dietary Polyphenols and Non-Alcoholic Fatty Liver Disease

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