Hyperglycemia-stimulating diet induces liver steatosis in sheep

Abstract Hepatic steatosis is strongly associated with chronic liver disease and systemic metabolic disorder. Adipose lipolysis is a recognized principal source of intrahepatic fat in various metabolic disorders, including non-alcoholic fatty liver disease. We hypothesized that, in the premorbid sta...

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Autores principales:	Mugagga Kalyesubula, Ramgopal Mopuri, Alexander Rosov, Tamir Alon, Nir Edery, Uzi Moallem, Hay Dvir
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/50c5163424224121a15cac57f3cef2f1
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spelling	oai:doaj.org-article:50c5163424224121a15cac57f3cef2f12021-12-02T16:26:21ZHyperglycemia-stimulating diet induces liver steatosis in sheep10.1038/s41598-020-68909-z2045-2322https://doaj.org/article/50c5163424224121a15cac57f3cef2f12020-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-68909-zhttps://doaj.org/toc/2045-2322Abstract Hepatic steatosis is strongly associated with chronic liver disease and systemic metabolic disorder. Adipose lipolysis is a recognized principal source of intrahepatic fat in various metabolic disorders, including non-alcoholic fatty liver disease. We hypothesized that, in the premorbid state, hepatic de novo lipogenesis (DNL) driven by excess carbohydrates abundance might play a more significant role. We employed a novel nutritional model in sheep of two distinct carbohydrates abundances. During 4 months of the dietary treatment, lambs were monitored for metabolic and terminal liver parameters. Lambs grown on the high-calorie (HC) diet were consistently more hyperglycemic and hyperinsulinemic than lambs grown on the lower-calorie (LC) diet (P < 0.0001). As a result, the HC lambs developed systemic- (HOMA-IR of 7.3 vs. 3.1; P < 0.0001), and adipose- (ADIPO-IR of 342.7 vs. 74.4; P < 0.0001) insulin resistance, significant adiposity (P < 0.0001), and higher plasma triglycerides (P < 0.05). Circulating leukocytes in the HC lambs had higher mRNA expression levels of the proinflammatory markers CCL2 (P < 0.01) and TNF-alpha (P < 0.04), and IL1B trended higher (P < 0.1). Remarkably, lambs on the HC diet developed substantial liver steatosis (mean fat content of 8.1 vs. 5.3% in the LC group; P < 0.0001) with a higher histological steatosis score (2.1 vs. 0.4; P < 0.0002). Hepatic steatosis was most-strongly associated with blood glucose and insulin levels but negatively correlated with circulating fatty acids—indicating a more significant contribution from hepatic DNL than from adipose lipolysis. Sheep may prove an attractive large-animal model of fatty liver and metabolic comorbidities resulting from excess carbohydrate-based energy early in life.Mugagga KalyesubulaRamgopal MopuriAlexander RosovTamir AlonNir EderyUzi MoallemHay DvirNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-12 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mugagga Kalyesubula Ramgopal Mopuri Alexander Rosov Tamir Alon Nir Edery Uzi Moallem Hay Dvir Hyperglycemia-stimulating diet induces liver steatosis in sheep
description	Abstract Hepatic steatosis is strongly associated with chronic liver disease and systemic metabolic disorder. Adipose lipolysis is a recognized principal source of intrahepatic fat in various metabolic disorders, including non-alcoholic fatty liver disease. We hypothesized that, in the premorbid state, hepatic de novo lipogenesis (DNL) driven by excess carbohydrates abundance might play a more significant role. We employed a novel nutritional model in sheep of two distinct carbohydrates abundances. During 4 months of the dietary treatment, lambs were monitored for metabolic and terminal liver parameters. Lambs grown on the high-calorie (HC) diet were consistently more hyperglycemic and hyperinsulinemic than lambs grown on the lower-calorie (LC) diet (P < 0.0001). As a result, the HC lambs developed systemic- (HOMA-IR of 7.3 vs. 3.1; P < 0.0001), and adipose- (ADIPO-IR of 342.7 vs. 74.4; P < 0.0001) insulin resistance, significant adiposity (P < 0.0001), and higher plasma triglycerides (P < 0.05). Circulating leukocytes in the HC lambs had higher mRNA expression levels of the proinflammatory markers CCL2 (P < 0.01) and TNF-alpha (P < 0.04), and IL1B trended higher (P < 0.1). Remarkably, lambs on the HC diet developed substantial liver steatosis (mean fat content of 8.1 vs. 5.3% in the LC group; P < 0.0001) with a higher histological steatosis score (2.1 vs. 0.4; P < 0.0002). Hepatic steatosis was most-strongly associated with blood glucose and insulin levels but negatively correlated with circulating fatty acids—indicating a more significant contribution from hepatic DNL than from adipose lipolysis. Sheep may prove an attractive large-animal model of fatty liver and metabolic comorbidities resulting from excess carbohydrate-based energy early in life.
format	article
author	Mugagga Kalyesubula Ramgopal Mopuri Alexander Rosov Tamir Alon Nir Edery Uzi Moallem Hay Dvir
author_facet	Mugagga Kalyesubula Ramgopal Mopuri Alexander Rosov Tamir Alon Nir Edery Uzi Moallem Hay Dvir
author_sort	Mugagga Kalyesubula
title	Hyperglycemia-stimulating diet induces liver steatosis in sheep
title_short	Hyperglycemia-stimulating diet induces liver steatosis in sheep
title_full	Hyperglycemia-stimulating diet induces liver steatosis in sheep
title_fullStr	Hyperglycemia-stimulating diet induces liver steatosis in sheep
title_full_unstemmed	Hyperglycemia-stimulating diet induces liver steatosis in sheep
title_sort	hyperglycemia-stimulating diet induces liver steatosis in sheep
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/50c5163424224121a15cac57f3cef2f1
work_keys_str_mv	AT mugaggakalyesubula hyperglycemiastimulatingdietinducesliversteatosisinsheep AT ramgopalmopuri hyperglycemiastimulatingdietinducesliversteatosisinsheep AT alexanderrosov hyperglycemiastimulatingdietinducesliversteatosisinsheep AT tamiralon hyperglycemiastimulatingdietinducesliversteatosisinsheep AT niredery hyperglycemiastimulatingdietinducesliversteatosisinsheep AT uzimoallem hyperglycemiastimulatingdietinducesliversteatosisinsheep AT haydvir hyperglycemiastimulatingdietinducesliversteatosisinsheep
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Hyperglycemia-stimulating diet induces liver steatosis in sheep

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