Effects of rabbit anti-α-melanocyte-stimulating hormone (α-MSH) immunoglobulins on α-MSH signaling related to food intake control.
Anti-α-melanocyte-stimulating hormone (α-MSH) polyclonal antibodies have been used for α-MSH neutralization in functional studies, but the results are sometime inconsistent with the antibody expected blocking properties. The present study aimed to determine if rabbit (Rb) anti-α-MSH immunoglobulins (Ig) may inhibit or enhance α-MSH signaling on melanocortin receptor type 4 (MC4R) and α-MSH-induced anorexigenic effect if presented as immune complexes with α-MSH. Polyclonal Rb anti-α-MSH IgG were commercially available and their ability to bind α-MSH has been confirmed by the immunohistochemical detection of α-MSH neurons in the rat hypothalamus. In vitro assay of the cyclic-adenosine mono-phosphate (cAMP) secreted by cells transfected with MC4R was performed to analyze effect of Rb IgG on α-MSH-induced cAMP production. We found that adding Rb IgG to α-MSH resulted in stimulation of cAMP detected at lower peptide concentrations as compared to α-MSH alone. To determine effects of Rb IgG on food intake, rats were injected into the arcuate hypothalamic nucleus with either α-MSH, Rb IgG alone or Rb IgG preincubated with α-MSH. During 2 days after injections, food intake was increased in both groups of rats receiving Rb IgG. However, during following 4 days when food was restricted to 1h/day, only the Rb IgG group displayed higher food intake. Furthermore, after the refeeding, 24h food intake was lower in rats receiving Rb IgG - α-MSH immune complexes. This group of rats was also characterized by higher number of immunopositive neurons in the arcuate nucleus expressing α-MSH and agouti-related protein but not tyrosine hydroxylase. Taken together, these results show that Rb anti-α-MSH antisera, although efficient for immunohistochemical detection of α-MSH, does not always display α-MSH blocking properties but, in contrast, may enhance α-MSH binding to MC4R and increase α-MSH anorexigenic effects when presented as immune complexes with the peptide.
Inserm UMR1073, Nutrition, Gut and Brain Laboratory, Rouen 76183, France; Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, Rouen 76183, France.
Nicolas
N
Lucas
Inserm UMR1073, Nutrition, Gut and Brain Laboratory, Rouen 76183, France; Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, Rouen 76183, France.
Romain
R
Legrand
Inserm UMR1073, Nutrition, Gut and Brain Laboratory, Rouen 76183, France; Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, Rouen 76183, France.
Wassila
W
Ouelaa
Inserm UMR1073, Nutrition, Gut and Brain Laboratory, Rouen 76183, France; Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, Rouen 76183, France.
Jonathan
J
Breton
Inserm UMR1073, Nutrition, Gut and Brain Laboratory, Rouen 76183, France; Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, Rouen 76183, France.
Naouel
N
Tennoune
Inserm UMR1073, Nutrition, Gut and Brain Laboratory, Rouen 76183, France; Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, Rouen 76183, France.
Christine
C
Bole-Feysot
Inserm UMR1073, Nutrition, Gut and Brain Laboratory, Rouen 76183, France; Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, Rouen 76183, France; Rouen University Hospital, CHU Charles Nicolle, 76183 Rouen, France.
Pierre
P
Déchelotte
Inserm UMR1073, Nutrition, Gut and Brain Laboratory, Rouen 76183, France; Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, Normandy University, Rouen 76183, France. Electronic address: Serguei.Fetissov@univ-rouen.fr.
Sergueï O
SO
Fetissov
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology*; D001069:Appetite Regulation / Q000187:drug effects*; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D044105:Receptor, Melanocortin, Type 4 / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000521:alpha-MSH / Q000276:immunology* / Q000494:pharmacology
D000906:Antibodies; C470072:MC4R protein, human; D044105:Receptor, Melanocortin, Type 4; D000521:alpha-MSH; D000242:Cyclic AMP
Affinity kinetics; Animal models; Autoantibodies; Energy homeostasis; Hypothalamus; Melanocortin system