Development of high-fat-diet-induced obesity in female metallothionein-null mice.
Oxidative stress accelerates adipocyte differentiation and lipid accumulation, leading to endoplasmic reticulum (ER) stress, which causes insulin resistance. Because metallothionein (MT) has a role in prevention of oxidative and ER stress, we examined the effects of MT on the development of obesity induced by 27 wk of a high-fat diet (HFD) in female MT-I- and MT-II-null (MT(-/-)) and wild-type (MT(+/+)) mice. Body weight, fat mass, and plasma cholesterol increased at a greater rate in MT(-/-) mice fed an HFD than in MT(-/-) mice fed a control diet (CD) and MT(+/+) mice fed an HFD, indicating that MT(-/-) mice fed an HFD became obese and hypercholesterolemic and that MT could prevent HFD-induced obesity. The observed increases in the levels of plasma leptin and leptin mRNA in the white adipose tissue of MT(-/-) mice fed the HFD suggested a leptin-resistant state. Enhanced expression of a mesoderm-specific transcript, which regulates the enlargement of fat cells, was accompanied by enlarged adipocytes in the white adipose tissue of young MT(-/-) mice before obesity developed after 3 and 8 wk of feeding the HFD. Thus, MT may have a preventive role against HFD-induced obesity by regulating adipocyte enlargement and leptin signaling.
Sato
Masao
M
Faculty of Pharmaceutical Sciences, Tokushima Bunri University, 180 Yamashiro-cho, Tokushima 770-8514, Japan. msato@ph.bunri-u.ac.jp
Kawakami
Takashige
T
Kondoh
Masuo
M
Takiguchi
Masufumi
M
Kadota
Yoshito
Y
Himeno
Seiichiro
S
Suzuki
Shinya
S
D017667:Adipocytes / Q000166:cytology; D000818:Animals; D048429:Cell Size; D004041:Dietary Fats / Q000494:pharmacology*; D005260:Female; D006937:Hypercholesterolemia / Q000209:etiology; D020738:Leptin / Q000032:analysis / Q000235:genetics; D008668:Metallothionein / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000139:chemically induced / Q000209:etiology*; D012333:RNA, Messenger / Q000032:analysis
D004041:Dietary Fats; D020738:Leptin; D012333:RNA, Messenger; D008668:Metallothionein