Fetuin B Is a Secreted Hepatocyte Factor Linking Steatosis to Impaired Glucose Metabolism

Meex, Ruth C. R.; Hoy, Andrew J.; Morris, Alexander; Brown, Russell D.; Lo, Janice; Burke, Melissa L.; Goode, Robert J. A.; Kingwell, Bronwyn A.; Kraakman, Michael J; Febbraio, Mark A.; Greve, J.W.M.; Rensen, Sander S.; Molloy, Mark P.; Lancaster, Graeme I.; Bruce, Clinton R.; Watt, Matthew J.

doi:10.1016/j.cmet.2015.09.023

Cited by 203 publications

(233 citation statements)

References 54 publications

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“…These investigators then showed both in in-vitro experiments and in mice that fetuin B impaired insulin action ex vivo in myotubes and in hepatocytes, and also caused glucose intolerance in-vivo in mice. As proof of concept that fetuin B was responsible for glucose intolerance in vivo, they then showed that silencing of fetuin B in the obese mice improved glucose tolerance in these animals [56]. Thus, these data strongly suggest that steatotic and inflamed liver is able to secrete a hepatokine that is capable of having an endocrine function beyond the liver to influence adversely glucose tolerance.…”

Section: Secreted Hepatokines and The Role Of Incretins And Glucagonmentioning

confidence: 87%

“…3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 9 Recent interest has also focussed on fetuin-B as a hepatokine that is capable of having an endocrine function beyond the liver to influence adversely insulin sensitivity and cause glucose tolerance. A recent study of 168 hepatokines, of which 32 were differentially secreted in steatotic versus non-steatotic hepatocytes showed that fetuin B was increased in humans with liver steatosis and in patients with type 2 diabetes [56]. These investigators then showed both in in-vitro experiments and in mice that fetuin B impaired insulin action ex vivo in myotubes and in hepatocytes, and also caused glucose intolerance in-vivo in mice.…”

Section: Secreted Hepatokines and The Role Of Incretins And Glucagonmentioning

confidence: 99%

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Risk of type 2 diabetes in patients with non-alcoholic fatty liver disease: Causal association or epiphenomenon?

Targher

Marchesini

Byrne

2016

Diabetes & Metabolism

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Nonalcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver diseases worldwide, causing considerable liverrelated mortality and morbidity. Over the last 10 years, it has also become increasingly evident that NAFLD is a multisystem disease, affecting many extra-hepatic organ systems and interacting with the regulation of multiple metabolic pathways. NAFLD is potentially involved in the aetiology and pathogenesis of type 2 diabetes via its direct contribution to hepatic/peripheral insulin resistance and the systemic release of multiple hepatokines that may adversely affect glucose metabolism and insulin action and secretion. In this updated review, we discuss the rapidly expanding body of clinical and epidemiological evidence that supports a strong link between NAFLD and the risk of developing type 2 diabetes. We also briefly examine the conventional and the more innovative pharmacological approaches for the treatment of NAFLD that may influence the risk of developing type 2 diabetes. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 2 AbstractNonalcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver diseases worldwide, causing considerable liver-related mortality and morbidity. Over the last 10 years, it has also become increasingly evident that NAFLD is a multisystem disease, affecting many extra-hepatic organ systems and interacting with the regulation of multiple metabolic pathways. NAFLD is potentially involved in the aetiology and pathogenesis of type 2 diabetes via its direct contribution to hepatic/peripheral insulin resistance and the systemic release of multiple hepatokines that may adversely affect glucose metabolism and insulin action and secretion. In this updated review, we discuss the rapidly expanding body of clinical and epidemiological evidence that supports a strong link between NAFLD and the risk of developing type 2 diabetes. We also briefly examine the conventional and the more innovative pharmacological approaches for the treatment of NAFLD that may influence the risk of developing type 2 diabetes.

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Section: Secreted Hepatokines and The Role Of Incretins And Glucagonmentioning

confidence: 87%

Section: Secreted Hepatokines and The Role Of Incretins And Glucagonmentioning

confidence: 99%

Risk of type 2 diabetes in patients with non-alcoholic fatty liver disease: Causal association or epiphenomenon?

Targher

Marchesini

Byrne

2016

Diabetes & Metabolism

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“…The present study was, to the best of our knowledge, the first to explore the relationships between Fetuin-B and CKD. Studies from Meex et al [10] and Zhu et al [11] suggested a potential association between Fetuin-B and liver steatosis. We found that the highest level of serum Fetuin-B was significantly associated with the highest prevalence of NAFLD, and our unpublished data suggested that serum Fetuin-B level was also positively correlated with intrahepatic TG content.…”

Section: Discussionmentioning

confidence: 99%

“…Fetuin-B, a kind of hepatokines, is known as the second member of the cystatin superfamily of cysteine protease inhibitors. Meex et al [10] reported that Fetuin-B was increased in humans with liver steatosis, impaired insulin action in myotubes and hepatocytes, and caused glucose intolerance in mice. Zhu et al [11] reported that serum Fetuin-B increased in subjects with NAFLD.…”

Section: Introductionmentioning

confidence: 99%

Fetuin-B Links Nonalcoholic Fatty Liver Disease to Chronic Kidney Disease in Obese Chinese Adults: A Cross-Sectional Study

Lin

Liu

et al. 2019

Ann Nutr Metab

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Background: There is no evidence available on the association of Fetuin-B with chronic kidney disease (CKD), and mechanisms linking nonalcoholic fatty liver disease (NAFLD) to CKD are not fully understood. We aimed to explore the independent associations and potential mechanisms of Fetuin-B and NAFLD with CKD. Methods: A cross-sectional study of 1,072 Chinese adults who underwent serum Fetuin-B test and hepatic ultrasonography scanning was conducted in Xiamen, China. CKD was defined as estimated glomerular filtration rate < 60 mL/min/1.73 m² and/or the presence of albuminuria. Results: Subjects with CKD showed significantly higher prevalence of NAFLD (69.5 vs. 57.2%, p < 0.001) and serum Fetuin-B levels (4.32 ± 1.45 vs. 4.05 ± 1.36 µg/mL, p = 0.007) than their controls. Increased serum Fetuin-B was also significantly associated with increased levels of fasting insulin and homeostasis model assessment – insulin resistance (both p values < 0.05). NAFLD and higher serum Fetuin-B were significantly associated with increased risk of CKD, and the unadjusted ORs (95% CIs) were 1.701 (1.256–2.303, p = 0.001) and 1.213 (1.053–1.399, p = 0.008, per SD increase of Fetuin-B), respectively. With adjustment for potential confounding factors, including metabolic/insulin resistance syndrome, NAFLD but not serum Fetuin-B was still significantly associated with increased risk of CKD, and the adjusted ORs (95% CIs) were 1.820 (1.327–2.496, p < 0.001) and 1.116 (0.959–1.298, p = 0.153, per SD increase of Fetuin-B), respectively. Conclusions: Fetuin-B might link NAFLD to CKD via inducing insulin resistance, and NAFLD contributes independently to the pathogenesis of CKD via multiple mechanisms besides of metabolic/insulin resistance syndrome.

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“…Проведено исследова-ние, в котором анализировались 168 гепатокинов, из ко-торых 32 секретировались гепатоцитами, пораженными при НАЖБП, и по его результатам сделан вывод, что фету-ин В был повышен у пациентов с НАЖБП и СД2 [32]. Эти-ми же исследователями показано в экспериментах in vitro и на мышах, что фетуин В ослабляет действие инсулина ex vivo в мышечных трубочках и гепатоцитах, а также вызы-вает толерантность к глюкозе у мышей in vivo.…”

Section: роль гепатокинов в развитии ирunclassified

Nonalcoholic fatty liver disease: cause or consequence of insulin resistance?

Mishina¹,

Mayorov²,

Богомолов³

et al. 2017

Diabetes mellitus

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Более 30 лет назад Ludwig J. (1980) описал заболева-ние, сходное с алкогольным стеатогепатитом, у пациентов с сахарным диабетом (СД), не употребляющих алкоголь, и назвал данное заболевание неалкогольным стеатогепа-титом (НАСГ) [1]. Неалкогольная жировая болезнь печени (НАЖБП) является самым распространенным хроническим заболеванием печени и приняла масштаб эпидемии, так же как ожирение и СД 2 типа (СД2) [2]. НАЖБП включает в себя спектр заболеваний от жирового гепатоза без признаков воспаления до НАСГ, цирроза печени и гепатоцеллюляр-ной карциномы [3]. ЭПИДЕМИОЛОГИЯОписанная распространенность НАЖБП широ-ко варьирует в зависимости от изучаемой популяции и от используе мого метода диагностики. Распространен-ность гистологически подтвержденной НАЖБП состав-ляет от 20 до 51%, однако, по данным ультразвукового метода исследования, НАЖБП встречается реже, от 17 до 46% [4] Неалкогольная жировая болезнь печени (НАЖБП) и сахарный диабет 2 типа (СД2) -патологические состояния, ассоцииро-ванные друг с другом и достигающие размеров эпидемии. Одним из наиболее значимых факторов риска развития как СД2, так и НАЖБП является ожирение, которое усиливает имеющуюся инсулинорезистентность (ИР). Последняя является ос-новным патогенетическим звеном СД2 и НАЖБП, связывая эти два патологических состояния. В настоящее время повышен интерес к поиску неинвазивных методик исследования; для оценки фиброза и определения показаний для биопсии печени неинвазивным методом используется Шкала оценки стадии фиброза при НАЖБП (NAFLD fibrosis score), расширенная панель фиброза печени (ELF) и транзиентная эластография. Однако золотым стандартом диагностики остается биопсия печени. Ввиду того, что у пациентов с СД чаще выявляется НАЖБП, чем в общей популяции, а также учитывая, что наличие СД явля-ется фактором риска прогрессии НАЖБП, данная когорта пациентов должна находиться под более тщательным контролем клиницистов. Данная обзорная работа посвящена поиску причинно-следственных связей таких коморбидных заболеваний, как НАЖБП и различные нарушения углеводного обмена, а также приоритетным направлениям диагностики НАЖБП.КЛЮЧЕВЫЕ СЛОВА: инсулинорезистентность; сахарный диабет; неалкогольная жировая болезнь печени; неалкогольный стеатогепатит; ожирение NONALCOHOLIC FATTY LIVER DISEASE: CAUSE OR CONSEQUENCE OF INSULIN RESISTANCE?© Ekaterina E. Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are pathological conditions that are co-occurring, and have been reaching epidemic proportions. One of the most significant risk factors for the development of both T2DM and NAFLD is obesity, which increases existing insulin resistance (IR). IR thought to be one of the main pathogenic causes linking T2DM and NAFLD. In recent years, there has been increased interest in obtaining non-invasive methods for assessing fibrosis and determining indications for liver biopsy, such as the NAFLD fibrosis score, extended liver fibrosis panel, and transient elastography. However, liver biopsy remains the gold standard for diagnosing NAFLD. Given that pa...

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Fetuin B Is a Secreted Hepatocyte Factor Linking Steatosis to Impaired Glucose Metabolism

Cited by 203 publications

References 54 publications

Risk of type 2 diabetes in patients with non-alcoholic fatty liver disease: Causal association or epiphenomenon?

Risk of type 2 diabetes in patients with non-alcoholic fatty liver disease: Causal association or epiphenomenon?

Fetuin-B Links Nonalcoholic Fatty Liver Disease to Chronic Kidney Disease in Obese Chinese Adults: A Cross-Sectional Study

Nonalcoholic fatty liver disease: cause or consequence of insulin resistance?

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