Mice lacking melanin-concentrating hormone are hypophagic and lean.
Feeding is influenced by hypothalamic neuropeptides that promote (orexigenic peptides) or inhibit feeding. Of these, neuropeptide Y (NPY) in the arcuate nucleus and melanin-concentrating hormone (MCH) and orexins/hypocretins in the lateral hypothalamus have received attention because their expression is increased during fasting and because they promote feeding when administered centrally. Surprisingly, absence of the orexigenic neuropeptide NPY fails to alter feeding or body weight in normal mice. As deficiency of a single component of the pathway that limits food intake (such as leptin or receptors for melanocortin-4) causes obesity, it has been suggested that orexigenic signals are more redundant than those limiting food intake. To define further the physiological role of MCH and to test the redundancy of orexigenic signals, we generated mice carrying a targeted deletion of the MCH gene. MCH-deficient mice have reduced body weight and leanness due to hypophagia (reduced feeding) and an inappropriately increased metabolic rate, despite their reduced amounts of both leptin and arcuate nucleus pro-opiomelanocortin messenger RNA. Our results show that MCH is a critical regulator of feeding and energy balance which acts downstream of leptin and the melanocortin system, and that deletion of a gene encoding a single orexigenic peptide can result in leanness.
Shimada
M
M
Division of Endocrinology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA.
Tritos
N A
NA
Lowell
B B
BB
Flier
J S
JS
Maratos-Flier
E
E
D000818:Animals; D002460:Cell Line; D004435:Eating; D002149:Energy Intake; D004734:Energy Metabolism; D005508:Food Deprivation; D017353:Gene Deletion; D007028:Hypothalamic Hormones / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007031:Hypothalamus / Q000378:metabolism; D020738:Leptin; D008543:Melanins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D010907:Pituitary Hormones / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013234:Stem Cells; D013851:Thinness
D007028:Hypothalamic Hormones; D020738:Leptin; D008543:Melanins; D009479:Neuropeptides; D010907:Pituitary Hormones; D011506:Proteins; D012333:RNA, Messenger; C019463:melanin-concentrating hormone