scholarly journals Adipocyte JAK2 Regulates Hepatic Insulin Sensitivity Independently of Body Composition, Liver Lipid Content, and Hepatic Insulin Signaling

Diabetes ◽  
2017 ◽  
Vol 67 (2) ◽  
pp. 208-221 ◽  
Author(s):  
Kevin C. Corbit ◽  
João Paulo G. Camporez ◽  
Lia R. Edmunds ◽  
Jennifer L. Tran ◽  
Nicholas B. Vera ◽  
...  
Keyword(s):  
Body Composition ◽  
Insulin Sensitivity ◽  
Lipid Content ◽  
Insulin Signaling ◽  
Liver Lipid ◽  
Hepatic Insulin Sensitivity ◽  
Liver Lipid Content ◽  
Hepatic Insulin Signaling

Abstract 12189: Molecular Mechanisms Underlying Fasting Modulated Liver Insulin Sensitivity and Metabolism in Male Lipodystrophic Bscl2/Seipin-Deficient Mice

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Weiqin Chen ◽  
Hongyi Zhou ◽  
Pradip Saha ◽  
Luge Li ◽  
Lawrence Chan
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Hepatic Steatosis ◽  
Insulin Signaling ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Liver Lipid ◽  
De Novo Lipogenesis ◽  
Hepatic Insulin Signaling ◽  
A Cell

Bscl2–/– mice recapitulate many of the major metabolic manifestations in Berardinelli-Seip Congenital Lipodystrophy type 2 (BSCL2) individuals, including lipodystrophy, hepatomegly, hepatic steatosis and insulin resistance. The mechanisms that underlie hepatic steatosis and insulin resistance in Bscl2–/– mice are poorly understood. To address this issue, we performed hyperinsulinemic-euglycemic clamp on Bscl2–/– and wild-type mice after an overnight (16-h) fast, and found that Bscl2–/– actually displayed increased hepatic insulin sensitivity. Interestingly, liver in Bscl2–/– mice after a short term (4-h) fast had impaired acute insulin signaling, a defect that disappeared after a 16-h fast. Notably, fasting dependent hepatic insulin signaling in Bscl2–/– mice was not associated with liver diacylglyceride and ceramide contents, but could be attributable in part to the expression of hepatic insulin signaling receptor and substrates. Meanwhile, increased de novo lipogenesis and decreased β-oxidation led to severe hepatic steatosis in fed or short fasted Bscl2–/– mice while liver lipid accumulation and metabolism in Bscl2–/– mice was markedly impacted by prolonged fasting. Furthermore, mice with liver-specific inactivation of Bscl2 manifested no hepatic steatosis even under high fat diet, suggesting Bscl2 does not play a cell autonomous role in regulating liver lipid homeostasis. Overall, our results offered new insights into the metabolic adaptations of liver in response to fasting and uncovered a novel fasting-dependent regulation of hepatic insulin signaling in a mouse model of human BSCL2.

scholarly journals Molecular Mechanisms Underlying Fasting Modulated Liver Insulin Sensitivity and Metabolism in Male Lipodystrophic Bscl2/Seipin-Deficient Mice

Endocrinology ◽  
2014 ◽  
Vol 155 (11) ◽  
pp. 4215-4225 ◽  
Author(s):  
Weiqin Chen ◽  
Hongyi Zhou ◽  
Pradip Saha ◽  
Luge Li ◽  
Lawrence Chan
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Hepatic Steatosis ◽  
Insulin Signaling ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Liver Lipid ◽  
De Novo Lipogenesis ◽  
Hepatic Insulin Signaling ◽  
A Cell

Abstract Bscl2 −/− mice recapitulate many of the major metabolic manifestations in Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) individuals, including lipodystrophy, hepatomegly, hepatic steatosis, and insulin resistance. The mechanisms that underlie hepatic steatosis and insulin resistance in Bscl2−/− mice are poorly understood. To address this issue, we performed hyperinsulinemic-euglycemic clamp on Bscl2−/− and wild-type mice after an overnight (16-h) fast, and found that Bscl2−/− actually displayed increased hepatic insulin sensitivity. Interestingly, liver in Bscl2−/− mice after a short term (4-h) fast had impaired acute insulin signaling, a defect that disappeared after a 16-hour fast. Notably, fasting-dependent hepatic insulin signaling in Bscl2−/− mice was not associated with liver diacylglyceride and ceramide contents, but could be attributable in part to the expression of hepatic insulin signaling receptor and substrates. Meanwhile, increased de novo lipogenesis and decreased β-oxidation led to severe hepatic steatosis in fed or short-fasted Bscl2−/− mice whereas liver lipid accumulation and metabolism in Bscl2−/− mice was markedly affected by prolonged fasting. Furthermore, mice with liver-specific inactivation of Bscl2 manifested no hepatic steatosis even under high-fat diet, suggesting Bscl2 does not play a cell autonomous role in regulating liver lipid homeostasis. Overall, our results offered new insights into the metabolic adaptations of liver in response to fasting and uncovered a novel fasting-dependent regulation of hepatic insulin signaling in a mouse model of human BSCL2.

scholarly journals Regulation of Mitochondria-Associated Membranes (MAMs) by NO/sGC/PKG Participates in the Control of Hepatic Insulin Response

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1319 ◽  
Author(s):  
Arthur Bassot ◽  
Marie-Agnès Chauvin ◽  
Nadia Bendridi ◽  
Jingwei Ji-Cao ◽  
Guillaume Vial ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Insulin Signaling ◽  
Soluble Guanylate Cyclase ◽  
Insulin Response ◽  
Cyclophilin D ◽  
Hepatic Insulin Sensitivity ◽  
Physiological Conditions ◽  
Huh7 Cells ◽  
The Impact

Under physiological conditions, nitric oxide (NO) produced by the endothelial NO synthase (eNOS) upregulates hepatic insulin sensitivity. Recently, contact sites between the endoplasmic reticulum and mitochondria named mitochondria-associated membranes (MAMs) emerged as a crucial hub for insulin signaling in the liver. As mitochondria are targets of NO, we explored whether NO regulates hepatic insulin sensitivity by targeting MAMs. In Huh7 cells, primary rat hepatocytes and mouse livers, enhancing NO concentration increased MAMs, whereas inhibiting eNOS decreased them. In vitro, those effects were prevented by inhibiting protein kinase G (PKG) and mimicked by activating soluble guanylate cyclase (sGC) and PKG. In agreement with the regulation of MAMs, increasing NO concentration improved insulin signaling, both in vitro and in vivo, while eNOS inhibition disrupted this response. Finally, inhibition of insulin signaling by wortmannin did not affect the impact of NO on MAMs, while experimental MAM disruption, using either targeted silencing of cyclophilin D or the overexpression of the organelle spacer fetal and adult testis-expressed 1 (FATE-1), significantly blunted the effects of NO on both MAMs and insulin response. Therefore, under physiological conditions, NO participates to the regulation of MAM integrity through the sGC/PKG pathway and concomitantly improves hepatic insulin sensitivity. Altogether, our data suggest that the induction of MAMs participate in the impact of NO on hepatocyte insulin response.

scholarly journals Prenatal hyperandrogenism induces alterations that affect liver lipid metabolism

2016 ◽  
Vol 230 (1) ◽  
pp. 67-79 ◽  
Author(s):  
Giselle Adriana Abruzzese ◽  
Maria Florencia Heber ◽  
Silvana Rocio Ferreira ◽  
Leandro Martin Velez ◽  
Roxana Reynoso ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Lipid Metabolism ◽  
Glucose Tolerance ◽  
Fatty Liver ◽  
Lipid Content ◽  
Liver Lipid ◽  
Acid Oxidation ◽  
Liver Lipid Content ◽  
Increased Risk ◽  
Liver Lipid Metabolism

Prenatal hyperandrogenism is hypothesized as one of the main factors contributing to the development of polycystic ovary syndrome (PCOS). PCOS patients have high risk of developing fatty liver and steatosis. This study aimed to evaluate the role of prenatal hyperandrogenism in liver lipid metabolism and fatty liver development. Pregnant rats were hyperandrogenized with testosterone. At pubertal age, the prenatally hyperandrogenized (PH) female offspring displayed both ovulatory (PHov) and anovulatory (PHanov) phenotypes that mimic human PCOS features. We evaluated hepatic transferases, liver lipid content, the balance between lipogenesis and fatty acid oxidation pathway, oxidant/antioxidant balance and proinflammatory status. We also evaluated the general metabolic status through growth rate curve, basal glucose and insulin levels, glucose tolerance test, HOMA-IR index and serum lipid profile. Although neither PH group showed signs of liver lipid content, the lipogenesis and fatty oxidation pathways were altered. The PH groups also showed impaired oxidant/antioxidant balance, a decrease in the proinflammatory pathway (measured by prostaglandin E2 and cyclooxygenase-2 levels), decreased glucose tolerance, imbalance of circulating lipids and increased risk of metabolic syndrome. We conclude that prenatal hyperandrogenism generates both PHov and PHanov phenotypes with signs of liver alterations, imbalance in lipid metabolism and increased risk of developing metabolic syndrome. The anovulatory phenotype showed more alterations in liver lipogenesis and a more impaired balance of insulin and glucose metabolism, being more susceptible to the development of steatosis.

Effect of Methionine on Liver Lipid Content and Lipid Metabolism of Rats Fed a Protein-free Diet

1973 ◽  
Vol 103 (1) ◽  
pp. 54-60 ◽  
Author(s):  
Yoritaka Aoyama ◽  
Masashi Nakanishi ◽  
Kiyoshi Ashida
Keyword(s):  
Lipid Metabolism ◽  
Lipid Content ◽  
Liver Lipid ◽  
Liver Lipid Content ◽  
Protein Free Diet

scholarly journals Apolipoprotein CIII Overexpression-Induced Hypertriglyceridemia Increases Nonalcoholic Fatty Liver Disease in Association with Inflammation and Cell Death

2017 ◽  
Vol 2017 ◽  
pp. 1-18 ◽  
Author(s):  
Adriene A. Paiva ◽  
Helena F. Raposo ◽  
Amarylis C. B. A. Wanschel ◽  
Tarlliza R. Nardelli ◽  
Helena C. F. Oliveira
Keyword(s):  
Cell Death ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Lipid Content ◽  
Fatty Liver Disease ◽  
Liver Lipid ◽  
Hepatic Insulin Resistance ◽  
Nonalcoholic Fatty Liver ◽  
Liver Lipid Content

Nonalcoholic fatty liver disease (NAFLD) is the principal manifestation of liver disease in obesity and metabolic syndrome. By comparing hypertriglyceridemic transgenic mice expressing apolipoprotein (apo) CIII with control nontransgenic (NTg) littermates, we demonstrated that overexpression of apoCIII, independent of a high-fat diet (HFD), produces NAFLD-like features, including increased liver lipid content; decreased antioxidant power; increased expression of TNFα, TNFα receptor, cleaved caspase-1, and interleukin-1β; decreased expression of adiponectin receptor-2; and increased cell death. This phenotype is aggravated and additional NAFLD features are differentially induced in apoCIII mice fed a HFD. HFD induced glucose intolerance together with increased gluconeogenesis, indicating hepatic insulin resistance. Additionally, the HFD led to marked increases in plasma TNFα (8-fold) and IL-6 (60%) in apoCIII mice. Cell death signaling (Bax/Bcl2), effector (caspase-3), and apoptosis were augmented in apoCIII mice regardless of whether a HFD or a low-fat diet was provided. Fenofibrate treatment reversed several of the effects associated with diet and apoCIII expression but did not normalize inflammatory traits even when liver lipid content was fully corrected. These results indicate that apoCIII and/or hypertriglyceridemia plays a major role in liver inflammation and cell death, which in turn increases susceptibility to and the severity of diet-induced NAFLD.

Endothelin antagonism improves hepatic insulin sensitivity associated with insulin signaling in Zucker fatty rats

Metabolism ◽  
2005 ◽  
Vol 54 (11) ◽  
pp. 1515-1523 ◽  
Author(s):  
Nathalie Berthiaume ◽  
Christian J. Carlson ◽  
Cristina M. Rondinone ◽  
Bradley A. Zinker
Keyword(s):  
Insulin Sensitivity ◽  
Insulin Signaling ◽  
Hepatic Insulin Sensitivity
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