Serum levels of human MIC-1/GDF15 vary in a diurnal pattern, do not display a profile suggestive of a satiety factor and are related to BMI

Vicky Wang-Wei Tsai; Laurence Macia; Christine Feinle-Bisset; Rakesh Manandhar; Arne Astrup; Anne Raben; Janne Kunchel Lorenzen; Peter T Schmidt; Fredrik Wiklund; Nancy L Pedersen; Lesley Campbell; Adamandia Kriketos; Aimin Xu; Zhou Pengcheng; Weiping Jia; Paul M G Curmi; Christopher N Angstmann; Ka Ki Michelle Lee-Ng; Hong Ping Zhang; Christopher P Marquis; Yasmin Husaini; Christoph Beglinger; Shu Lin; Herbert Herzog; David A Brown; Amanda Sainsbury; Samuel N Breit

doi:10.1371/journal.pone.0133362

Serum levels of human MIC-1/GDF15 vary in a diurnal pattern, do not display a profile suggestive of a satiety factor and are related to BMI

Vicky Wang-Wei Tsai, Laurence Macia, Christine Feinle-Bisset, Rakesh Manandhar, Arne Astrup, Anne Raben, Janne Kunchel Lorenzen, Peter T Schmidt, Fredrik Wiklund, Nancy L Pedersen, Lesley Campbell, Adamandia Kriketos, Aimin Xu, Zhou Pengcheng, Weiping Jia, Paul M G Curmi, Christopher N Angstmann, Ka Ki Michelle Lee-Ng, Hong Ping Zhang, Christopher P MarquisYasmin Husaini, Christoph Beglinger, Shu Lin, Herbert Herzog, David A Brown, Amanda Sainsbury, Samuel N Breit

Obesity Research

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Abstract

The TGF-b superfamily cytokine MIC-1/GDF15 circulates in the blood of healthy humans. Its levels rise substantially in cancer and other diseases and this may sometimes lead to development of an anorexia/cachexia syndrome. This is mediated by a direct action of MIC-1/GDF15 on feeding centres in the hypothalamus and brainstem. More recent studies in germline gene deleted mice also suggest that this cytokine may play a role in physiological regulation of energy homeostasis. To further characterize the role of MIC-1/GDF15 in physiological regulation of energy homeostasis in man, we have examined diurnal and food associated variation in serum levels and whether variation in circulating levels relate to BMI in human monozygotic twin pairs. We found that the within twin pair differences in serum MIC-1/GDF15 levels were significantly correlated with within twin pair differences in BMI, suggesting a role for MIC-1/GDF15 in the regulation of energy balance in man. MIC-1/GDF15 serum levels altered slightly in response to a meal, but comparison with variation its serum levels over a 24hour period suggested that these changes are likely to be due to bimodal diurnal variation which can alter serum MIC-1/GDF15 levels by about plus or minus 10% from the mesor. The lack of a rapid and substantial postprandial increase in MIC-1/GDF15 serum levels suggests that MIC1/GDF15 is unlikely to act as a satiety factor. Taken together, our findings suggest that MIC-1/GDF15 may be a physiological regulator of energy homeostasis in man, most probably due to actions on long-term regulation of energy homeostasis.

Original language	English
Article number	e0133362
Journal	P L o S One
Volume	10
Issue number	7
Number of pages	15
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0133362
Publication status	Published - 24 Jul 2015

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Tsai, V. W-W., Macia, L., Feinle-Bisset, C., Manandhar, R., Astrup, A., Raben, A., Lorenzen, J. K., Schmidt, P. T., Wiklund, F., Pedersen, N. L., Campbell, L., Kriketos, A., Xu, A., Pengcheng, Z., Jia, W., Curmi, P. M. G., Angstmann, C. N., Lee-Ng, K. K. M., Zhang, H. P., ... Breit, S. N. (2015). Serum levels of human MIC-1/GDF15 vary in a diurnal pattern, do not display a profile suggestive of a satiety factor and are related to BMI. P L o S One, 10(7), [e0133362]. https://doi.org/10.1371/journal.pone.0133362

Tsai, VW-W, Macia, L, Feinle-Bisset, C, Manandhar, R, Astrup, A, Raben, A, Lorenzen, JK, Schmidt, PT, Wiklund, F, Pedersen, NL, Campbell, L, Kriketos, A, Xu, A, Pengcheng, Z, Jia, W, Curmi, PMG, Angstmann, CN, Lee-Ng, KKM, Zhang, HP, Marquis, CP, Husaini, Y, Beglinger, C, Lin, S, Herzog, H, Brown, DA, Sainsbury, A & Breit, SN 2015, 'Serum levels of human MIC-1/GDF15 vary in a diurnal pattern, do not display a profile suggestive of a satiety factor and are related to BMI', P L o S One, vol. 10, no. 7, e0133362. https://doi.org/10.1371/journal.pone.0133362

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title = "Serum levels of human MIC-1/GDF15 vary in a diurnal pattern, do not display a profile suggestive of a satiety factor and are related to BMI",

abstract = "The TGF-b superfamily cytokine MIC-1/GDF15 circulates in the blood of healthy humans. Its levels rise substantially in cancer and other diseases and this may sometimes lead to development of an anorexia/cachexia syndrome. This is mediated by a direct action of MIC-1/GDF15 on feeding centres in the hypothalamus and brainstem. More recent studies in germline gene deleted mice also suggest that this cytokine may play a role in physiological regulation of energy homeostasis. To further characterize the role of MIC-1/GDF15 in physiological regulation of energy homeostasis in man, we have examined diurnal and food associated variation in serum levels and whether variation in circulating levels relate to BMI in human monozygotic twin pairs. We found that the within twin pair differences in serum MIC-1/GDF15 levels were significantly correlated with within twin pair differences in BMI, suggesting a role for MIC-1/GDF15 in the regulation of energy balance in man. MIC-1/GDF15 serum levels altered slightly in response to a meal, but comparison with variation its serum levels over a 24hour period suggested that these changes are likely to be due to bimodal diurnal variation which can alter serum MIC-1/GDF15 levels by about plus or minus 10% from the mesor. The lack of a rapid and substantial postprandial increase in MIC-1/GDF15 serum levels suggests that MIC1/GDF15 is unlikely to act as a satiety factor. Taken together, our findings suggest that MIC-1/GDF15 may be a physiological regulator of energy homeostasis in man, most probably due to actions on long-term regulation of energy homeostasis.",

author = "Tsai, {Vicky Wang-Wei} and Laurence Macia and Christine Feinle-Bisset and Rakesh Manandhar and Arne Astrup and Anne Raben and Lorenzen, {Janne Kunchel} and Schmidt, {Peter T} and Fredrik Wiklund and Pedersen, {Nancy L} and Lesley Campbell and Adamandia Kriketos and Aimin Xu and Zhou Pengcheng and Weiping Jia and Curmi, {Paul M G} and Angstmann, {Christopher N} and Lee-Ng, {Ka Ki Michelle} and Zhang, {Hong Ping} and Marquis, {Christopher P} and Yasmin Husaini and Christoph Beglinger and Shu Lin and Herbert Herzog and Brown, {David A} and Amanda Sainsbury and Breit, {Samuel N}",

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T1 - Serum levels of human MIC-1/GDF15 vary in a diurnal pattern, do not display a profile suggestive of a satiety factor and are related to BMI

AU - Tsai, Vicky Wang-Wei

AU - Macia, Laurence

AU - Feinle-Bisset, Christine

AU - Manandhar, Rakesh

AU - Astrup, Arne

AU - Raben, Anne

AU - Lorenzen, Janne Kunchel

AU - Schmidt, Peter T

AU - Wiklund, Fredrik

AU - Pedersen, Nancy L

AU - Campbell, Lesley

AU - Kriketos, Adamandia

AU - Xu, Aimin

AU - Pengcheng, Zhou

AU - Jia, Weiping

AU - Curmi, Paul M G

AU - Angstmann, Christopher N

AU - Lee-Ng, Ka Ki Michelle

AU - Zhang, Hong Ping

AU - Marquis, Christopher P

AU - Husaini, Yasmin

AU - Beglinger, Christoph

AU - Lin, Shu

AU - Herzog, Herbert

AU - Brown, David A

AU - Sainsbury, Amanda

AU - Breit, Samuel N

N1 - CURIS 2015 NEXS 259

PY - 2015/7/24

Y1 - 2015/7/24

N2 - The TGF-b superfamily cytokine MIC-1/GDF15 circulates in the blood of healthy humans. Its levels rise substantially in cancer and other diseases and this may sometimes lead to development of an anorexia/cachexia syndrome. This is mediated by a direct action of MIC-1/GDF15 on feeding centres in the hypothalamus and brainstem. More recent studies in germline gene deleted mice also suggest that this cytokine may play a role in physiological regulation of energy homeostasis. To further characterize the role of MIC-1/GDF15 in physiological regulation of energy homeostasis in man, we have examined diurnal and food associated variation in serum levels and whether variation in circulating levels relate to BMI in human monozygotic twin pairs. We found that the within twin pair differences in serum MIC-1/GDF15 levels were significantly correlated with within twin pair differences in BMI, suggesting a role for MIC-1/GDF15 in the regulation of energy balance in man. MIC-1/GDF15 serum levels altered slightly in response to a meal, but comparison with variation its serum levels over a 24hour period suggested that these changes are likely to be due to bimodal diurnal variation which can alter serum MIC-1/GDF15 levels by about plus or minus 10% from the mesor. The lack of a rapid and substantial postprandial increase in MIC-1/GDF15 serum levels suggests that MIC1/GDF15 is unlikely to act as a satiety factor. Taken together, our findings suggest that MIC-1/GDF15 may be a physiological regulator of energy homeostasis in man, most probably due to actions on long-term regulation of energy homeostasis.

AB - The TGF-b superfamily cytokine MIC-1/GDF15 circulates in the blood of healthy humans. Its levels rise substantially in cancer and other diseases and this may sometimes lead to development of an anorexia/cachexia syndrome. This is mediated by a direct action of MIC-1/GDF15 on feeding centres in the hypothalamus and brainstem. More recent studies in germline gene deleted mice also suggest that this cytokine may play a role in physiological regulation of energy homeostasis. To further characterize the role of MIC-1/GDF15 in physiological regulation of energy homeostasis in man, we have examined diurnal and food associated variation in serum levels and whether variation in circulating levels relate to BMI in human monozygotic twin pairs. We found that the within twin pair differences in serum MIC-1/GDF15 levels were significantly correlated with within twin pair differences in BMI, suggesting a role for MIC-1/GDF15 in the regulation of energy balance in man. MIC-1/GDF15 serum levels altered slightly in response to a meal, but comparison with variation its serum levels over a 24hour period suggested that these changes are likely to be due to bimodal diurnal variation which can alter serum MIC-1/GDF15 levels by about plus or minus 10% from the mesor. The lack of a rapid and substantial postprandial increase in MIC-1/GDF15 serum levels suggests that MIC1/GDF15 is unlikely to act as a satiety factor. Taken together, our findings suggest that MIC-1/GDF15 may be a physiological regulator of energy homeostasis in man, most probably due to actions on long-term regulation of energy homeostasis.

U2 - 10.1371/journal.pone.0133362

DO - 10.1371/journal.pone.0133362

M3 - Journal article

C2 - 26207898

SN - 1932-6203

VL - 10

JO - PLoS Computational Biology

JF - PLoS Computational Biology

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M1 - e0133362

ER -

Serum levels of human MIC-1/GDF15 vary in a diurnal pattern, do not display a profile suggestive of a satiety factor and are related to BMI

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