title: Deficient copper concentrations in dried-defatted hepatic tissue from ob/ob mice: A potential model for study of defective copper regulation in metabolic liver disease.
abstract: Ob/ob mice provide an animal model for non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH) in patients with obesity and type-2 diabetes. Low liver copper has been linked to hepatic lipid build-up (steatosis) in animals with systemic copper deficiency caused by low-copper diets. However, hepatic copper status in patients with NAFLD or NASH is uncertain, and a validated animal model useful for the study of hepatic copper regulation in common forms of metabolic liver disease is lacking. Here, we report parallel measurements of essential metal levels in whole-liver tissue and defatted-dried liver tissue from ob/ob and non-obese control mice. Measurements in whole-liver tissue from ob/ob mice at an age when they have developed NAFLD/NASH, provide compelling evidence for factitious lowering of copper and all other essential metals by steatosis, and so cannot be used to study hepatic metal regulation in this model. By marked contrast, metal measurements in defatted-dried liver samples reveal that most essential metals were actually normal and indicate specific lowering of copper in ob/ob mice, consistent with hepatic copper deficiency. Thus ob/ob mice can provide a model useful for the study of copper regulation in NAFLD and NASH, provided levels are measured in defatted-dried liver tissue.
authors: Centre for Advanced Discovery and Experimental Therapeutics, Central Manchester University Hospitals NHS Foundation Trust (CMFT), Manchester M13 9WL, United Kingdom; Centre for Endocrinology & Diabetes, Institute of Human Development, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom.
authors: Stephanie J
authors: SJ
authors: Church
authors: Centre for Advanced Discovery and Experimental Therapeutics, Central Manchester University Hospitals NHS Foundation Trust (CMFT), Manchester M13 9WL, United Kingdom; Centre for Endocrinology & Diabetes, Institute of Human Development, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom.
authors: Paul
authors: P
authors: Begley
authors: Centre for Advanced Discovery and Experimental Therapeutics, Central Manchester University Hospitals NHS Foundation Trust (CMFT), Manchester M13 9WL, United Kingdom; Centre for Endocrinology & Diabetes, Institute of Human Development, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom.
authors: Nina
authors: N
authors: Kureishy
authors: Centre for Advanced Discovery and Experimental Therapeutics, Central Manchester University Hospitals NHS Foundation Trust (CMFT), Manchester M13 9WL, United Kingdom; Centre for Endocrinology & Diabetes, Institute of Human Development, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom.
authors: Selina
authors: S
authors: McHarg
authors: Centre for Advanced Discovery and Experimental Therapeutics, Central Manchester University Hospitals NHS Foundation Trust (CMFT), Manchester M13 9WL, United Kingdom; Centre for Endocrinology & Diabetes, Institute of Human Development, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom.
authors: Paul N
authors: PN
authors: Bishop
authors: Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom.
authors: David A
authors: DA
authors: Bechtold
authors: Centre for Advanced Discovery and Experimental Therapeutics, Central Manchester University Hospitals NHS Foundation Trust (CMFT), Manchester M13 9WL, United Kingdom; Centre for Endocrinology & Diabetes, Institute of Human Development, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom. Electronic address: r.unwin@manchester.ac.uk.
authors: Richard D
authors: RD
authors: Unwin
authors: Centre for Advanced Discovery and Experimental Therapeutics, Central Manchester University Hospitals NHS Foundation Trust (CMFT), Manchester M13 9WL, United Kingdom; Centre for Endocrinology & Diabetes, Institute of Human Development, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom; School of Biological Sciences, Faculty of Science, and Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand; Department of Pharmacology, Medical Sciences Division, University of Oxford, Oxford OX1 3QT, United Kingdom. Electronic address: g.cooper@auckland.ac.nz.
authors: Garth J S
authors: GJ
authors: Cooper
mesh_terms: D000818:Animals; D003300:Copper / Q000378:metabolism*; D005223:Fats / Q000302:isolation & purification*; D008099:Liver / Q000378:metabolism*; D008107:Liver Diseases / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D005223:Fats; D003300:Copper
keywords: Copper; Diabetes; Liver; Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis; Obesity