TY - JOUR
T1 - TGF-b Superfamily Cytokine MIC-1/GDF15 Is a Physiological Appetite and Body Weight Regulator
AU - Tsai, Vicky Wang Wei
AU - Macia, Laurence
AU - Johnen, Heiko
AU - Kuffner, Tamara
AU - Manadhar, Rakesh
AU - Jørgensen, Sebastian Beck
AU - Lee-Ng, Ka Ki Michelle
AU - Zhang, Hong Ping
AU - Wu, Liyun
AU - Marquis, Christopher Peter
AU - Jiang, Lele
AU - Husaini, Yasmin
AU - Lin, Shu
AU - Herzog, Herbert
AU - Brown, David A.
AU - Sainsbury, Amanda
AU - Breit, Samuel N.
PY - 2013/2/28
Y1 - 2013/2/28
N2 - The TGF-b superfamily cytokine MIC-1/GDF15 circulates in all humans and when overproduced in cancer leads to anorexia/cachexia, by direct action on brain feeding centres. In these studies we have examined the role of physiologically relevant levels of MIC-1/GDF15 in the regulation of appetite, body weight and basal metabolic rate. MIC-1/GDF15 gene knockout mice (MIC-1-/-) weighed more and had increased adiposity, which was associated with increased spontaneous food intake. Female MIC-1-/- mice exhibited some additional alterations in reduced basal energy expenditure and physical activity, possibly owing to the associated decrease in total lean mass. Further, infusion of human recombinant MIC-1/GDF15 sufficient to raise serum levels in MIC-1-/- mice to within the normal human range reduced body weight and food intake. Taken together, our findings suggest that MIC-1/GDF15 is involved in the physiological regulation of appetite and energy storage.
AB - The TGF-b superfamily cytokine MIC-1/GDF15 circulates in all humans and when overproduced in cancer leads to anorexia/cachexia, by direct action on brain feeding centres. In these studies we have examined the role of physiologically relevant levels of MIC-1/GDF15 in the regulation of appetite, body weight and basal metabolic rate. MIC-1/GDF15 gene knockout mice (MIC-1-/-) weighed more and had increased adiposity, which was associated with increased spontaneous food intake. Female MIC-1-/- mice exhibited some additional alterations in reduced basal energy expenditure and physical activity, possibly owing to the associated decrease in total lean mass. Further, infusion of human recombinant MIC-1/GDF15 sufficient to raise serum levels in MIC-1-/- mice to within the normal human range reduced body weight and food intake. Taken together, our findings suggest that MIC-1/GDF15 is involved in the physiological regulation of appetite and energy storage.
UR - http://www.scopus.com/inward/record.url?scp=84874520918&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0055174
DO - 10.1371/journal.pone.0055174
M3 - Article
C2 - 23468844
AN - SCOPUS:84874520918
SN - 1932-6203
VL - 8
JO - PLoS One
JF - PLoS One
IS - 2
M1 - e55174
ER -
