Evidence for hypothalamic dysregulation in mouse models of anorexia as well as in humans.
Eating disorders constitute major medical health problems in the western world. Even though little is known about the molecular mechanisms behind abnormal eating behavior, it has become clear that the central nervous system (CNS), particularly the hypothalamus, plays a significant role. The anorexic anx/anx mouse is a unique model for studying food intake and energy expenditure. The anx mutation is linked to marked alterations in hypothalamic distributions of signal substances known to have potent regulatory roles in the control of food intake. Another mouse model that displays an anorectic phenotype similar to the anx/anx mouse is the Contactin KO mouse. This model displays very similar hypothalamic alterations as seen in the anx/anx mouse, arguing for a role of these specific hypothalamic changes in an anorectic phenotype. In human eating disorders, hypothalamic systems corresponding to those defective in mouse models could be compromised since autoantibodies against melanocortin peptides have been detected in anorectic and bulimic patients. These findings represent research avenues that may lead to a better understanding of eating disorders and development of targeted therapeutic approaches.
Johansen
Jeanette E
JE
Karolinska Institutet, Department of Molecular Medicine and Surgery, L8:00, Karolinska University Hospital, S-171 76 Stockholm, Sweden. jeanette.johansen@ki.se
Fetissov
Sergueï O
SO
Bergström
Ulrika
U
Nilsson
Ida
I
Faÿ
Charles
C
Ranscht
Barbara
B
Hökfelt
Tomas
T
Schalling
Martin
M
D000818:Animals; D000855:Anorexia / Q000276:immunology / Q000503:physiopathology*; D001069:Appetite Regulation / Q000502:physiology*; D001323:Autoantibodies / Q000276:immunology; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000502:physiology*; D058966:Contactins; D004195:Disease Models, Animal; D005247:Feeding Behavior / Q000502:physiology; D006801:Humans; D007031:Hypothalamus / Q000502:physiology / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D000521:alpha-MSH / Q000276:immunology
D001323:Autoantibodies; D015816:Cell Adhesion Molecules, Neuronal; D058966:Contactins; D000521:alpha-MSH