Nonalcoholic Fatty Liver Disease Impairs the Liver–Alpha Cell Axis Independent of Hepatic Inflammation and Fibrosis

Pedersen, Julie Steen; Rygg, Marte Opseth; Kristiansen, Viggo B.; Olsen, Beth Hærstedt; Serizawa, Reza; Holst, Jens J.; Madsbad, Sten; Gluud, Lise Lotte; Bendtsen, Flemming; Albrechtsen, Nicolai J. Wewer

doi:10.1002/hep4.1562

Cited by 30 publications

(25 citation statements)

References 44 publications

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“…In line with this, the hyperglucagonemia observed in most subjects with type 2 diabetes is associated with hyperaminoacidemia. Especially, elevated plasma levels of alanine seem to mark a disturbed liver–alpha cell axis [ 85 , 88 , 89 , 90 ], and alanine also appears to be a potent glucagonotropic amino acid [ 91 ]. Importantly, hyperglucagonemia seems to be associated with a fatty liver rather than with diabetes per se [ 92 ], and plasma concentrations of glucagon and non-branched-chain amino acids are characteristically increased in subjects with increased liver fat (as reflected by elevated HOMA-IR levels) [ 85 ].…”

Section: The Liver–alpha Cell Axis May Be Impaired In Nafldmentioning

confidence: 99%

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

Galsgaard

2020

JCM

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A key criterion for the most common chronic liver disease—non-alcoholic fatty liver disease (NAFLD)—is an intrahepatic fat content above 5% in individuals who are not using steatogenic agents or having significant alcohol intake. Subjects with NAFLD have increased plasma concentrations of glucagon, and emerging evidence indicates that subjects with NAFLD may show hepatic glucagon resistance. For many years, glucagon has been thought of as the counterregulatory hormone to insulin with a primary function of increasing blood glucose concentrations and protecting against hypoglycemia. However, in recent years, glucagon has re-emerged as an important regulator of other metabolic processes including lipid and amino acid/protein metabolism. This review discusses the evidence that in NAFLD, hepatic glucagon resistance may result in a dysregulated lipid and amino acid/protein metabolism, leading to excess accumulation of fat, hyperglucagonemia, and increased oxidative stress contributing to the worsening/progression of NAFLD.

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Section: The Liver–alpha Cell Axis May Be Impaired In Nafldmentioning

confidence: 99%

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

Galsgaard

2020

JCM

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“…On the other hand, the association between steatosis and IS impairment is also well-established (Yki-Jarvinen, 2014). Obviously, sCD163 may originate from macrophages both in the liver and adipose tissues, and both fat mass as well as inflammation in the liver and adipose tissue was greatly reduced 12 months after RYGB (Pedersen et al, 2020). However, we have previously shown a sCD163 gradient across the liver in morbidly obese patients supportive of a considerable production by hepatic macrophages (Kazankov et al, 2015).…”

Section: Discussionmentioning

confidence: 88%

Macrophage activation marker sCD163 is associated with liver injury and hepatic insulin resistance in obese patients before and after Roux‐en‐Y gastric bypass

Kazankov

Bojsen‐Møller

Møller

et al. 2022

Physiological Reports

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“…The development of hepatic steatosis occurs at the same time as increased free fatty acids, free cholesterol, and other lipid metabolites, leading to an increased lipotoxicity. This can lead to mitochondrial dysfunction with oxidative stress and hormonal disturbances [ 28 ]. The pathogenesis is complex and not yet fully understood.…”

Section: Discussionmentioning

confidence: 99%

Referral Patterns for Patients with Nonalcoholic Fatty Liver Disease

Rashu

Werge

Hetland

et al. 2021

JCM

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The incidence of nonalcoholic fatty liver disease (NAFLD) is rapidly increasing. This study evaluates the referral pattern of patients with NAFLD. A cohort study evaluating all patients with NAFLD referred to a single Gastroenterology Department from January 2017 to June 2020. Electronic patient referral letters were reviewed, and patients with NAFLD were diagnosed using standardized tests as part of a prospective cohort study. Predictors of nonalcoholic steatohepatitis (NASH) with significant (≥F2) fibrosis were evaluated in logistic regression analyses. In total, 323 (18.6%) of 1735 patients referred to the Gastro Unit during the study period were diagnosed with NAFLD. Patients were referred from general practitioners (62.5%) or other hospital departments (37.5%). Most referral letters included information suggesting a possible diagnosis of NAFLD (patient history, blood tests, or diagnostic imaging) or used the nonspecific general diagnosis suspected disease (Z.038). Out of 110 patients referred for a liver biopsy, 71 (22%) had NASH with significant fibrosis (F2 n = 39, F3 n = 19, F4 n = 13). Thirty-nine of these patients were referred from the primary sector. A logistic regression analysis (adjusted for age and gender) including all 323 patients showed that type 2 diabetes was the only significant independent predictor of NASH with fibrosis.

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Nonalcoholic Fatty Liver Disease Impairs the Liver–Alpha Cell Axis Independent of Hepatic Inflammation and Fibrosis

Abstract: Patients with non‐alcoholic fatty liver disease (NAFLD) have insulin as well as glucagon resistance but glucagon resistance toward amino acid metabolism is independent of NAFLD severity. Bariatric surgery normalizes insulin but not glucagon resistance in patients with NASH.

Cited by 30 publications

References 44 publications

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

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

Macrophage activation marker sCD163 is associated with liver injury and hepatic insulin resistance in obese patients before and after Roux‐en‐Y gastric bypass

Referral Patterns for Patients with Nonalcoholic Fatty Liver Disease

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