title: Overexpression of the adiponectin gene mimics the metabolic and stress resistance effects of calorie restriction, but not the anti-tumor effect.
abstract: Adiponectin (Adipoq), a peptide hormone secreted from the white adipose tissue, may play a role in the anti-aging and/or anti-tumor effects of calorie restriction (CR). We analyzed metabolic traits in Adipoq gene-overexpressing mice fed ad libitum with a regular diet (RD) or a high-fat diet (HFD), or fed 30% CR of RD initiated at 12 weeks of age. Adipoq-RD and -HFD mice at 6 months of age showed reduced blood glucose and insulin concentrations, and thus increased insulin sensitivity, compared with WT mice fed a RD or a HFD. In the epididymal white adipose tissue in Adipoq mice, senescence-like changes such as upregulation of p53 protein and of biomarkers of inflammation, Cd68 and Ccl2 mRNA, were ameliorated compared with WT-RD and WT-HFD mouse tissues. Resistance to stress induced by lipopolysaccharide was also strengthened in Adipoq mice compared with WT mice. These metabolic changes and stress resistance were also noted in the WT-CR mice, suggesting that Adipoq plays a part in the effect of CR. In contrast, in an allograft tumor growth model, tumor growth was not inhibited in Adipoq mice. The present findings suggest that Adipoq plays a part in the anti-aging, but not in the anti-tumor, effects of CR.
authors.affiliation: Department of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Nagasaki, 852-8523, Japan; Department of Surgical Oncology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Nagasaki, 852-8501, Japan.
authors.forename: Ryotaro
authors.initials: R
authors.lastname: Kamohara
authors.affiliation: Department of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Nagasaki, 852-8523, Japan.
authors.forename: Haruyoshi
authors.initials: H
authors.lastname: Yamaza
authors.affiliation: Department of Surgical Oncology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Nagasaki, 852-8501, Japan.
authors.forename: Tomoshi
authors.initials: T
authors.lastname: Tsuchiya
authors.affiliation: Department of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Nagasaki, 852-8523, Japan.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Komatsu
authors.affiliation: Department of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Nagasaki, 852-8523, Japan.
authors.forename: Seongjoon
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Nagasaki, 852-8523, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Hayashi
authors.affiliation: Department of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Nagasaki, 852-8523, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Chiba
authors.affiliation: Department of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Nagasaki, 852-8523, Japan.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Mori
authors.affiliation: Department of Medicine, Kurume University School of Medicine, Kurume, 811-1346, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Otabe
authors.affiliation: Department of Medicine, Kurume University School of Medicine, Kurume, 811-1346, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Department of Surgical Oncology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Nagasaki, 852-8501, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nagayasu
authors.affiliation: Department of Pathology, Nagasaki University School of Medicine and Graduate School of Biomedical Sciences, Nagasaki, 852-8523, Japan. Electronic address: shimo@nagasaki-u.ac.jp.
authors.forename: Isao
authors.initials: I
authors.lastname: Shimokawa
mesh_terms: D052242:Adiponectin / Q000235:genetics / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000378:metabolism*; D015415:Biomarkers; D031204:Caloric Restriction; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D059305:Diet, High-Fat; D005260:Female; D015870:Gene Expression; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D052242:Adiponectin; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D018932:Chemokine CCL2; D007328:Insulin; D012333:RNA, Messenger; C499919:Adipoq protein, mouse; C081026:CD68 protein, mouse; D000097382:CD68 Molecule; C491768:Ccl2 protein, mouse
keywords: Adiponectin; Calorie restriction; ER stress; Insulin; Tumor growth; p53