Melanocortin receptors mediate leptin effects on feeding and body weight but not adipose apoptosis.
The melanocortin (MC) system is a known downstream mediator of leptin signaling in the brain; thus, activation of MC receptors by melanotan II (MTII), a MC3/4 receptor agonist, was hypothesized to increase adipose apoptosis, a phenomenon seen after leptin treatments. To test this hypothesis, male Sprague-Dawley rats received pretreatments of intracerebroventricular injections of artificial cerebrospinal fluid (aCSF, 5 microl) or SHU9119 (1.0 nmol/5 microl), an MC3/4 receptor antagonist. One hour later, aCSF (5 microl), leptin (10 microg/5 microl), or MTII (0.1 nmol/5 microl) was injected intracerebroventricularly in the aCSF-pretreated groups, and either leptin (10 microg/5 microl) or MTII (0.1 nmol/5 microl) was injected intracerebroventricularly in SHU9119-pretreated groups. Each pair of treatments was given once daily for four successive days. Body weight (BW), food intake (FI), and body temperature (BT) were measured daily at 4- and 24-h intervals. SHU9119 completely prevented the decrease in FI and BW caused by either MTII or leptin. Muscle mass remained unchanged regardless of treatment, but both leptin and MTII significantly reduced mass of inguinal (iWAT), retroperitoneal (rWAT), and epididymal (eWAT) white adipose tissues (P<.05). SHU9119 prevented the decrease in mass of intrascapular brown fat, iWAT, and rWAT (P<.05). Leptin, but not MTII, increased DNA fragmentation in eWAT (P<.05), but SHU9119 pretreatment had no effect on leptin-induced apoptosis. Thus, although the MC receptors in the brain are involved in mediating actions of leptin on FI, fat mass, and BW, leptin-induced adipose apoptosis is regulated independently of MC receptors.
Choi
Yang-Ho
YH
Departments of Animal and Dairy Science and Food and Nutrition, University of Georgia, 444 Animal Science Complex, Athens, GA 30602-2771, USA.
Li
ChangLong
C
Page
Karen
K
Westby
Alisha
A
Della-Fera
Mary Anne
MA
Lin
Ji
J
Hartzell
Diane L
DL
Baile
Clifton A
CA
D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001823:Body Composition / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology*; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology*; D007276:Injections, Intraventricular; D020738:Leptin / Q000008:administration & dosage / Q000502:physiology*; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000008:administration & dosage; D010456:Peptides, Cyclic / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D044101:Receptors, Melanocortin / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction; D000521:alpha-MSH / Q000008:administration & dosage / Q000031:analogs & derivatives*
D020738:Leptin; D010456:Peptides, Cyclic; D044101:Receptors, Melanocortin; C079282:melanotan-II; C103272:SHU 9119; D000521:alpha-MSH; D009074:Melanocyte-Stimulating Hormones