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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.

Tsai VW, 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 PM, Angstmann CN, Lee-Ng KK, Zhang HP, Marquis CP, Husaini Y, Beglinger C, Lin S, Herzog H, Brown DA, Sainsbury A, Breit SN - PLoS ONE (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: St Vincent's Centre for Applied Medical Research, St Vincent's Hospital and University of New South Wales, Sydney, NSW, Australia.

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 24 hour 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.

No MeSH data available.


Related in: MedlinePlus

Correlation of monozygotic within-pair differences in MIC-1/GDF15 serum levels and within-pair differences in BMI.Correlation between within twin-pair difference in serum MIC-1/GDF15 levels and within twin-pair difference in BMI (n = 72 twins), performed by Spearman regression, identifies a highly significant correlation. In general the twin of the twin pair with a higher serum MIC-1/GDF15 level generally had a lower BMI than their identical twin pair. The reverse was also true.
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pone.0133362.g001: Correlation of monozygotic within-pair differences in MIC-1/GDF15 serum levels and within-pair differences in BMI.Correlation between within twin-pair difference in serum MIC-1/GDF15 levels and within twin-pair difference in BMI (n = 72 twins), performed by Spearman regression, identifies a highly significant correlation. In general the twin of the twin pair with a higher serum MIC-1/GDF15 level generally had a lower BMI than their identical twin pair. The reverse was also true.

Mentions: To investigate whether MIC-1/GDF15 may regulate energy homeostasis in humans, as in mice, we examined the relationship between MIC-1/GDF15 serum levels and BMI. To increase the sensitivity of our analysis we examined genetically identical, non-obese monozygous twins from the Swedish twin cohort [21, 22, 31] with the aim of eliminating the effect of heritable variables and reducing disease-related confounding factors. The within-pair difference in serum MIC-1/GFDF15 levels was inversely correlated with the within-pair difference in BMI (n = 72 twin pairs, r = 0.426 and p = 0.0016) (Fig 1). For example, this means that when one twin had a higher serum MIC-1/GDF15 level than his/her identical sibling, the BMI was generally lower than that of the sibling. The reverse was also true. These data suggest that in non-obese human subjects, MIC-1/GDF15 may regulate BMI independently of genetic background. Furthermore, the observed correlation between MIC-1/GDF15 serum levels and BMI in humans suggests that the data we have previously obtained in mice, demonstrating that high MIC-1/GDF15 levels lead to weight loss and that absent MIC-1/GDF15 levels leads to weight gain[23], may also apply to humans.


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.

Tsai VW, 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 PM, Angstmann CN, Lee-Ng KK, Zhang HP, Marquis CP, Husaini Y, Beglinger C, Lin S, Herzog H, Brown DA, Sainsbury A, Breit SN - PLoS ONE (2015)

Correlation of monozygotic within-pair differences in MIC-1/GDF15 serum levels and within-pair differences in BMI.Correlation between within twin-pair difference in serum MIC-1/GDF15 levels and within twin-pair difference in BMI (n = 72 twins), performed by Spearman regression, identifies a highly significant correlation. In general the twin of the twin pair with a higher serum MIC-1/GDF15 level generally had a lower BMI than their identical twin pair. The reverse was also true.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4514813&req=5

pone.0133362.g001: Correlation of monozygotic within-pair differences in MIC-1/GDF15 serum levels and within-pair differences in BMI.Correlation between within twin-pair difference in serum MIC-1/GDF15 levels and within twin-pair difference in BMI (n = 72 twins), performed by Spearman regression, identifies a highly significant correlation. In general the twin of the twin pair with a higher serum MIC-1/GDF15 level generally had a lower BMI than their identical twin pair. The reverse was also true.
Mentions: To investigate whether MIC-1/GDF15 may regulate energy homeostasis in humans, as in mice, we examined the relationship between MIC-1/GDF15 serum levels and BMI. To increase the sensitivity of our analysis we examined genetically identical, non-obese monozygous twins from the Swedish twin cohort [21, 22, 31] with the aim of eliminating the effect of heritable variables and reducing disease-related confounding factors. The within-pair difference in serum MIC-1/GFDF15 levels was inversely correlated with the within-pair difference in BMI (n = 72 twin pairs, r = 0.426 and p = 0.0016) (Fig 1). For example, this means that when one twin had a higher serum MIC-1/GDF15 level than his/her identical sibling, the BMI was generally lower than that of the sibling. The reverse was also true. These data suggest that in non-obese human subjects, MIC-1/GDF15 may regulate BMI independently of genetic background. Furthermore, the observed correlation between MIC-1/GDF15 serum levels and BMI in humans suggests that the data we have previously obtained in mice, demonstrating that high MIC-1/GDF15 levels lead to weight loss and that absent MIC-1/GDF15 levels leads to weight gain[23], may also apply to humans.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: St Vincent's Centre for Applied Medical Research, St Vincent's Hospital and University of New South Wales, Sydney, NSW, Australia.

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 24 hour 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.

No MeSH data available.


Related in: MedlinePlus