Effects of growth hormone (GH) on mRNA levels of uncoupling proteins 1, 2, and 3 in brown and white adipose tissues and skeletal muscle in obese mice.
We have investigated whether GH treatment influences the expression of UCP1, 2 and 3 mRNA in a KK-Ay obese mouse model. KK-Ay mice (n = 10) and C57Bl/6J control mice (n = 10) were injected subcutaneously with human GH (1.0 mg/kg/day and 3.5 mg/kg/day) for 10 days, and compared with mice injected with physical saline. The KK-Ay obese mice weighed significantly less (p < 0.01 : 1.0 mg/kg/day, p < 0.05 : 3.5 mg/kg/day) and had smaller inguinal subcutaneous and perimetric white adipose tissue (WAT) pads (p < 0.05 : 3.5 mg/kg/day), but increased skeletal muscle weight (p < 0.05). The brown adipose tissue (BAT) weight did not change significantly. Not only plasma free fatty acid and glucose levels but also plasma insulin levels decreased. The reduced HOMA-IR (homeostasis model assessment-insulin resistance) values suggested that insulin resistance was improved by GH treatment. UCP1 mRNA levels increased after the 3.5 mg GH treatment by 2.8-fold (p < 0.01 vs. saline controls) and 2.0-fold (p < 0.05 vs. 1 mg GH treatment) in BAT, and by 6.0-fold in subcutaneous WAT (p < 0.05 vs. controls). UCP2 mRNA levels increased 2.2-fold (p < 0.05 vs. control) and 2.1-fold (p < 0.05 vs. 1 mg GH treatment) in BAT, and 2.0-fold (p < 0.05 vs. controls) in skeletal muscle. One mg GH administration also stimulated UCP1 mRNA expression by 2.5-fold (p < 0.05 vs. controls) and UCP3 mRNA expression by 2.8-fold (p < 0.05 vs. controls) in the muscle. On the other hand, lean mice showed no significant difference in body composition or plasma parameters. UCP1, 2 and 3 mRNA expression in lean mice did not show any significant change after treatment with GH. We conclude that GH treatment increased mRNA levels for not only UCP1, but also UCP 2 and 3 in BAT, WAT and muscle in a KK-Ay obese mouse model. These findings suggest that GH-induced thermogenesis may contribute to the reduction in WAT and energy expenditure.
Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Japan. chioki@koto.kpu-m.ac.jp
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C
Hioki
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Yoshida
A
A
Kogure
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Takakura
T
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Umekawa
K
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Yoshioka
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Shimatsu
T
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Yoshikawa
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001769:Blood / Q000187:drug effects; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D013006:Growth Hormone / Q000494:pharmacology*; D006801:Humans; D007473:Ion Channels; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009765:Obesity / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3
D002352:Carrier Proteins; D007473:Ion Channels; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; C000604371:UCP1 protein, human; C000604389:UCP2 protein, human; C000604392:UCP3 protein, human; C000604372:Ucp1 protein, mouse; C000604390:Ucp2 protein, mouse; C000604393:Ucp3 protein, mouse; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; D013006:Growth Hormone