The effects of the melanocortin agonist (MT-II) on subcutaneous and visceral adipose tissue in rodents.
The melanocortin system is a critical pathway in the regulation of energy balance. In this study, we analyzed the peripheral effects of the synthetic melanocortin agonist melanotan-II (MT-II) in rodents fed a low-fat or high-fat diet. MT-II-treated high-fat diet-induced obese (DIO) mice lost weight and body fat, whereas MT-II-treated low-fat-fed mice maintained their original body weight. Specifically, MT-II treatment led to a general reduction in both visceral and subcutaneous adipose tissue in high-fat-fed mice compared with Vehicle (ad libitum) controls. Vehicle-treated pair-fed DIO mice lost an equivalent amount of body weight compared with MT-II-treated mice but retained more adipose tissue. Pair-fed mice showed a reduction in visceral adipose tissue and no effect on subcutaneous adipose tissue compared with MT-II-treated mice. It is surprising that subcutaneous lean mass was significantly reduced in the pairfed mice. The data were replicated in DIO rats and indicated that MT-II treatment led to a generalized reduction in adipose tissue. These results indicate that peripheral MT-II treatment leads to weight loss that affects both the visceral and subcutaneous fat compartments. This finding illustrates the complexity of analyzing weight-reducing compounds. Although the present data suggest that the anorectic effect of MT-II is primarily a consequence of reduced food intake, the body composition data suggest that other mechanisms are involved.
Strader
April D
AD
University of Cincinnati School of Medicine, Cincinnati, Ohio, USA. astrader@siumed.edu
Shi
Haifei
H
Ogawa
Ryuichi
R
Seeley
Randy J
RJ
Reizes
Ofer
O
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D050152:Intra-Abdominal Fat / Q000187:drug effects*; D053486:Melanocortins / Q000819:agonists*; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000188:drug therapy; D010456:Peptides, Cyclic / Q000494:pharmacology*; D050151:Subcutaneous Fat / Q000187:drug effects*; D000521:alpha-MSH / Q000031:analogs & derivatives* / Q000494:pharmacology
D053486:Melanocortins; D010456:Peptides, Cyclic; C079282:melanotan-II; D000521:alpha-MSH