BACKGROUND: Chronic kidney disease (CKD) results in hypertriglyceridemia which is largely due to impaired clearance of triglyceride-rich lipoproteins occasioned by downregulation of lipoprotein lipase and very low-density lipoprotein (LDL) receptor in the skeletal muscle and adipose tissue and of hepatic lipase and LDL receptor-related protein in the liver. However, data on the effect of CKD on fatty acid metabolism in the liver is limited and was investigated here. METHODS: Male Sprague-Dawley rats were randomized to undergo 5/6 nephrectomy (CRF) or sham operation (control) and observed for 12 weeks. The animals were then euthanized and their liver tissue tested for nuclear translocation (activation) of carbohydrate-responsive element binding protein (ChREBP) and sterol-responsive element binding protein-1 (SREBP-1) which independently regulate the expression of key enzyme in fatty acid synthesis, i.e. fatty acid synthase (FAS) and acyl-CoA carboxylase (ACC) as well as nuclear Peroxisome proliferator-activated receptor alpha (PPARα) which regulates the expression of enzymes involved in fatty acid oxidation and transport, i.e. L-FABP and CPT1A. In addition, the expression of ATP synthase α, ATP synthase β, glycogen synthase and diglyceride acyltransferase 1 (DGAT1) and DGAT2 were determined. RESULTS: Compared with controls, the CKD rats exhibited hypertriglyceridemia, elevated plasma and liver tissue free fatty acids, increased nuclear ChREBP and reduced nuclear SREBP-1 and PPARα, upregulation of ACC and FAS and downregulation of L-FABP, CPT1A, ATP synthase α, glycogen synthase and DGAT in the liver tissue. CONCLUSION: Liver in animals with advanced CKD exhibits ChREBP-mediated upregulation of enzymes involved in fatty acid synthesis, downregulation of PPARα-regulated fatty acid oxidation system and reduction of DGAT resulting in reduced fatty acid incorporation in triglyceride.
BACKGROUND:Chronic kidney disease (CKD) results in hypertriglyceridemia which is largely due to impaired clearance of triglyceride-rich lipoproteins occasioned by downregulation of lipoprotein lipase and very low-density lipoprotein (LDL) receptor in the skeletal muscle and adipose tissue and of hepatic lipase and LDL receptor-related protein in the liver. However, data on the effect of CKD on fatty acid metabolism in the liver is limited and was investigated here. METHODS: Male Sprague-Dawley rats were randomized to undergo 5/6 nephrectomy (CRF) or sham operation (control) and observed for 12 weeks. The animals were then euthanized and their liver tissue tested for nuclear translocation (activation) of carbohydrate-responsive element binding protein (ChREBP) and sterol-responsive element binding protein-1 (SREBP-1) which independently regulate the expression of key enzyme in fatty acid synthesis, i.e. fatty acid synthase (FAS) and acyl-CoA carboxylase (ACC) as well as nuclear Peroxisome proliferator-activated receptor alpha (PPARα) which regulates the expression of enzymes involved in fatty acid oxidation and transport, i.e. L-FABP and CPT1A. In addition, the expression of ATP synthase α, ATP synthase β, glycogen synthase and diglyceride acyltransferase 1 (DGAT1) and DGAT2 were determined. RESULTS: Compared with controls, the CKD rats exhibited hypertriglyceridemia, elevated plasma and liver tissue free fatty acids, increased nuclear ChREBP and reduced nuclear SREBP-1 and PPARα, upregulation of ACC and FAS and downregulation of L-FABP, CPT1A, ATP synthase α, glycogen synthase and DGAT in the liver tissue. CONCLUSION: Liver in animals with advanced CKD exhibits ChREBP-mediated upregulation of enzymes involved in fatty acid synthesis, downregulation of PPARα-regulated fatty acid oxidation system and reduction of DGAT resulting in reduced fatty acid incorporation in triglyceride.
Authors: Per-Ola Attman; Ola Samuelsson; Ann-Cathrine Johansson; James B Moberly; Petar Alaupovic Journal: Kidney Int Suppl Date: 2003-05 Impact factor: 10.545
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Authors: Giovanni Musso; Roberto Gambino; James H Tabibian; Mattias Ekstedt; Stergios Kechagias; Masahide Hamaguchi; Rolf Hultcrantz; Hannes Hagström; Seung Kew Yoon; Phunchai Charatcharoenwitthaya; Jacob George; Francisco Barrera; Svanhildur Hafliðadóttir; Einar Stefan Björnsson; Matthew J Armstrong; Laurence J Hopkins; Xin Gao; Sven Francque; An Verrijken; Yusuf Yilmaz; Keith D Lindor; Michael Charlton; Robin Haring; Markus M Lerch; Rainer Rettig; Henry Völzke; Seungho Ryu; Guolin Li; Linda L Wong; Mariana Machado; Helena Cortez-Pinto; Kohichiroh Yasui; Maurizio Cassader Journal: PLoS Med Date: 2014-07-22 Impact factor: 11.069
Authors: Esther Nkuipou-Kenfack; Flore Duranton; Nathalie Gayrard; Àngel Argilés; Ulrika Lundin; Klaus M Weinberger; Mohammed Dakna; Christian Delles; William Mullen; Holger Husi; Julie Klein; Thomas Koeck; Petra Zürbig; Harald Mischak Journal: PLoS One Date: 2014-05-09 Impact factor: 3.240