Melanin-concentrating hormone receptor 1 deficiency increases insulin sensitivity in obese leptin-deficient mice without affecting body weight.
The hypothalamic peptide melanin-concentrating hormone (MCH) plays important roles in energy homeostasis. Animals overexpressing MCH develop hyperphagia, obesity, and insulin resistance. In this study, mice lacking both the MCH receptor-1 (MCHr1 knockout) and leptin (ob/ob) double-null mice (MCHr1 knockout ob/ob) were generated to investigate whether the obesity and/or the insulin resistance linked to the obese phenotype of ob/ob mice was attenuated by ablation of the MCHr1 gene. In MCHr1 knockout ob/ob mice an oral glucose load resulted in a lower blood glucose response and markedly lower insulin levels compared with the ob/ob mice despite no differences in body weight, food intake, or energy expenditure. In addition, MCHr1 knockout ob/ob mice had higher locomotor activity and lean body mass, lower body fat mass, and altered body temperature regulation compared with ob/ob mice. In conclusion, MCHr1 is important for insulin sensitivity and/or secretion via a mechanism not dependent on decreased body weight.
Bjursell
Mikael
M
Department of Physiology and Pharmacology, Gothenburg University, Sweden. mikael.bjursell@astrazeneca.com
Gerdin
Anna-Karin
AK
Ploj
Karolina
K
Svensson
David
D
Svensson
Lennart
L
Oscarsson
Jan
J
Snaith
Michael
M
Törnell
Jan
J
Bohlooly-Y
Mohammad
M
D000818:Animals; D001823:Body Composition; D001833:Body Temperature Regulation; D001835:Body Weight; D003346:Corticotropin-Releasing Hormone / Q000032:analysis; D004435:Eating; D005947:Glucose / Q000378:metabolism; D007333:Insulin Resistance; D020738:Leptin / Q000172:deficiency*; D051379:Mice; D008820:Mice, Obese; D009043:Motor Activity; D009765:Obesity / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D054411:Receptors, Leptin; D017481:Receptors, Somatostatin / Q000172:deficiency / Q000502:physiology*; D013230:Stearoyl-CoA Desaturase / Q000235:genetics
D020738:Leptin; C491209:Mchr1 protein, mouse; D012333:RNA, Messenger; D054411:Receptors, Leptin; D017481:Receptors, Somatostatin; C515447:leptin receptor, mouse; D003346:Corticotropin-Releasing Hormone; D013230:Stearoyl-CoA Desaturase; D005947:Glucose