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To establish whether diabetes or obesity is more closely associated with <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content> fibrosis, we compared diabetic <jats:italic>foz\/foz<\/jats:italic> C57<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>6\/J with non\u2010diabetic <jats:italic>foz\/foz <\/jats:italic><jats:styled-content style=\"fixed-case\">BALB<\/jats:styled-content>\/c mice. We also determined hepatic cytokines, growth factors and related profibrotic pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Male and female <jats:italic>foz\/foz <\/jats:italic><jats:styled-content style=\"fixed-case\">BALB<\/jats:styled-content>\/c and C57<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>6\/J mice were fed <jats:styled-content style=\"fixed-case\">HF<\/jats:styled-content> or chow for 24\u00a0weeks before determining metabolic indices, liver injury, cytokines, growth factors, pathology\/fibrosis and matrix deposition pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All <jats:italic>foz\/foz<\/jats:italic> mice were obese. Hepatomegaly, hyperinsulinemia, hyperglycaemia and hypoadiponectinaemia occurred only in <jats:italic>foz\/foz<\/jats:italic> C57BL6\/J mice, whereas <jats:italic>foz\/foz<\/jats:italic> BALB\/c formed more adipose. Serum ALT, steatosis, ballooning, liver inflammation and NAFLD activity score were worse in C57BL6\/J mice. In HF\u2010fed mice, fibrosis was severe in <jats:italic>foz\/foz<\/jats:italic> C57BL6\/J, appreciable in WT C57BL6\/J, but absent in <jats:italic>foz\/foz<\/jats:italic> BALB\/c mice. Hepatic <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> expression of TNF\u2010\u03b1, IL\u201012, IL\u20104, IL\u201010 was increased (but not IFN\u2010\u03b3, IL\u20101\u03b2, IL\u201017A), and IL\u20104:IFN\u2010\u03b3 ratio (indicating Th\u20102 predominance) was higher in HF\u2010fed <jats:italic>foz\/foz<\/jats:italic> C57BL6\/J than BALB\/c mice. In livers of HF\u2010fed <jats:italic>foz\/foz<\/jats:italic> C57BL6\/J mice, TGF\u2010\u03b2 was unaltered but PDGF\u03b1 and CTGF were increased in association with enhanced \u03b1\u2010SMA, CD147and MMP activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In mice with equivalent genetic\/dietary obesity, <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content> development is linked to strain differences in hyperinsulinaemia and hyperglycaemia inversely related to lipid partitioning between adipose and liver. Diabetes\u2010mediated <jats:styled-content style=\"fixed-case\">CTGF<\/jats:styled-content>\u2010regulation of <jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>s as well as cytokines\/growth factors (Th\u20102 cytokine predominant, <jats:styled-content style=\"fixed-case\">PDGF<\/jats:styled-content>\u03b1, not <jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content>\u2010\u03b2) mobilized in the resultant hepatic necroinflammatory change may contribute to strain differences in <jats:styled-content style=\"fixed-case\">NASH<\/jats:styled-content> fibrosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.12335","type":"journal-article","created":{"date-parts":[[2013,10,12]],"date-time":"2013-10-12T01:02:35Z","timestamp":1381539755000},"page":"1084-1093","source":"Crossref","is-referenced-by-count":84,"title":["Strain dependence of diet\u2010induced <scp>NASH<\/scp> and liver fibrosis in obese mice is linked to diabetes and inflammatory phenotype"],"prefix":"10.1111","volume":"34","author":[{"given":"Geoffrey C.","family":"Farrell","sequence":"first","affiliation":[{"name":"Liver Research Group Australian National University Medical School at The Canberra Hospital Garran ACT Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Auvro R.","family":"Mridha","sequence":"additional","affiliation":[{"name":"Liver Research Group Australian National University Medical School at The Canberra Hospital Garran ACT Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew M.","family":"Yeh","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Washington Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todor","family":"Arsov","sequence":"additional","affiliation":[{"name":"Liver Research Group Australian National University Medical School at The Canberra Hospital Garran ACT Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derrick M.","family":"Van Rooyen","sequence":"additional","affiliation":[{"name":"Liver Research Group Australian National University Medical School at The Canberra Hospital Garran ACT Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Brooling","sequence":"additional","affiliation":[{"name":"Liver Research Group Australian National University Medical School at The Canberra Hospital Garran ACT Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tori","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Liver Research Group Australian National University Medical School at The Canberra Hospital Garran ACT Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Heydet","sequence":"additional","affiliation":[{"name":"Liver Research Group Australian National University Medical School at The Canberra 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