title: Defective adipose tissue development associated with hepatomegaly in cathepsin E-deficient mice fed a high-fat diet.
abstract: Cathepsin E is an intracellular aspartic proteinase, which is predominantly distributed in immune-related and epithelial cells. However, the role of the enzyme in adipose tissues remains unknown. In this study, we investigated the characteristics of cathepsin E-deficient (CatE(-/-)) mice fed a high-fat diet (HFD), as a mouse model of obesity. HFD-fed CatE(-/-) mice displayed reduced body weight gain and defective development of white adipose tissue (WAT) and brown adipose tissue (BAT), compared with HFD-fed wild-type mice. Moreover, fat-induced CatE(-/-) mice showed abnormal lipid accumulation in non-adipose tissues characterized by hepatomegaly, which is probably due to defective adipose tissue development. Detailed pathological and biochemical analyses showed that hepatomegaly was accompanied by hepatic steatosis and hypercholesterolemia in HFD-induced CatE(-/-) mice. In fat-induced CatE(-/-) mice, the number of macrophages infiltrating into WAT was significantly lower than in fat-induced wild-type mice. Thus, the impaired adipose tissue development in HFD-induced CatE(-/-) mice was probably due to reduced infiltration of macrophages and may lead to hepatomegaly accompanied by hepatic steatosis and hypercholesterolemia.
authors.affiliation: Research Promotion Section, Nagasaki University, Nagasaki 852-8521, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kadowaki
authors.affiliation: Department of Molecular Cell Biology and Oral Anatomy, Graduate School of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Mizuho A
authors.initials: MA
authors.lastname: Kido
authors.affiliation: Department of Molecular Cell Biology and Oral Anatomy, Graduate School of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Hatakeyama
authors.affiliation: Division of Oral Pathopharmacology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8588, Japan.
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Okamoto
authors.affiliation: Division of Oral Pathopharmacology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8588, Japan. Electronic address: tsuta@nagasaki-u.ac.jp.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Tsukuba
authors.affiliation: Proteolysis Research Laboratory, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D050156:Adipogenesis / Q000235:genetics / Q000502:physiology; D000273:Adipose Tissue / Q000201:enzymology* / Q000473:pathology*; D002001:Adipose Tissue, Brown / Q000201:enzymology / Q000473:pathology; D052436:Adipose Tissue, White / Q000201:enzymology / Q000473:pathology; D000818:Animals; D020059:Cathepsin E / Q000172:deficiency* / Q000235:genetics; D059305:Diet, High-Fat / Q000009:adverse effects; D005234:Fatty Liver / Q000209:etiology / Q000473:pathology; D006529:Hepatomegaly / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D006937:Hypercholesterolemia / Q000209:etiology; D050356:Lipid Metabolism; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000201:enzymology / Q000209:etiology / Q000473:pathology
chemical_list: D020059:Cathepsin E; C533926:Ctse protein, mouse
keywords: Adipose tissue; Cathepsin E; High-fat diet