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TGF-b superfamily cytokine MIC-1/GDF15 is a physiological appetite and body weight regulator.

Tsai VW, Macia L, Johnen H, Kuffner T, Manadhar R, Jørgensen SB, Lee-Ng KK, Zhang HP, Wu L, Marquis CP, Jiang L, Husaini Y, Lin S, Herzog H, Brown DA, Sainsbury A, Breit SN - PLoS ONE (2013)

Bottom Line: 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.

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, New South Wales, Australia.

ABSTRACT
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.

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MIC-1−/− are heavier than MIC-1+/+ mice.(A) Male and (B) female MIC-1−/− mice and syngeneic control MIC-1+/+ mice were weighed once every four weeks from age of 4 weeks to 1 year. Both male and female MIC-1−/− mice were on average 6–10% heavier than the MIC-1+/+ mice (male n = 13/group, p = 0.04; female n = 13/group, p = 0.01 repeated measures ANOVA). The weight difference between genotypes appeared from the age of 4 weeks with increased weight differences with ageing in both (C) male and (D) female mice (male n = 13/group, p = 0.044, r2 = 0.32; female n = 13/group p<0.001, r2 = 0.55, linear regression). Data expressed as mean ± SE.
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pone-0055174-g001: MIC-1−/− are heavier than MIC-1+/+ mice.(A) Male and (B) female MIC-1−/− mice and syngeneic control MIC-1+/+ mice were weighed once every four weeks from age of 4 weeks to 1 year. Both male and female MIC-1−/− mice were on average 6–10% heavier than the MIC-1+/+ mice (male n = 13/group, p = 0.04; female n = 13/group, p = 0.01 repeated measures ANOVA). The weight difference between genotypes appeared from the age of 4 weeks with increased weight differences with ageing in both (C) male and (D) female mice (male n = 13/group, p = 0.044, r2 = 0.32; female n = 13/group p<0.001, r2 = 0.55, linear regression). Data expressed as mean ± SE.

Mentions: To investigate whether MIC-1/GDF15 might contribute to the physiological regulation of energy homeostasis, the body weight of MIC-1−/− mice and syngeneic controls were monitored between the ages of 4 weeks to 1 year. Male MIC-1−/− mice were on average 6±0.6% heavier than male MIC-1+/+ control mice of the same age, and female MIC-1−/− mice weighed on average 10±0.7% more than female controls (Fig. 1A and 1B, male p = 0.04; female p = 0.01). For both male and female mice, the weight differences between genotypes increased significantly over time (Fig. 1C and 1D, female p<0.01; male p = 0.04).


TGF-b superfamily cytokine MIC-1/GDF15 is a physiological appetite and body weight regulator.

Tsai VW, Macia L, Johnen H, Kuffner T, Manadhar R, Jørgensen SB, Lee-Ng KK, Zhang HP, Wu L, Marquis CP, Jiang L, Husaini Y, Lin S, Herzog H, Brown DA, Sainsbury A, Breit SN - PLoS ONE (2013)

MIC-1−/− are heavier than MIC-1+/+ mice.(A) Male and (B) female MIC-1−/− mice and syngeneic control MIC-1+/+ mice were weighed once every four weeks from age of 4 weeks to 1 year. Both male and female MIC-1−/− mice were on average 6–10% heavier than the MIC-1+/+ mice (male n = 13/group, p = 0.04; female n = 13/group, p = 0.01 repeated measures ANOVA). The weight difference between genotypes appeared from the age of 4 weeks with increased weight differences with ageing in both (C) male and (D) female mice (male n = 13/group, p = 0.044, r2 = 0.32; female n = 13/group p<0.001, r2 = 0.55, linear regression). Data expressed as mean ± SE.
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pone-0055174-g001: MIC-1−/− are heavier than MIC-1+/+ mice.(A) Male and (B) female MIC-1−/− mice and syngeneic control MIC-1+/+ mice were weighed once every four weeks from age of 4 weeks to 1 year. Both male and female MIC-1−/− mice were on average 6–10% heavier than the MIC-1+/+ mice (male n = 13/group, p = 0.04; female n = 13/group, p = 0.01 repeated measures ANOVA). The weight difference between genotypes appeared from the age of 4 weeks with increased weight differences with ageing in both (C) male and (D) female mice (male n = 13/group, p = 0.044, r2 = 0.32; female n = 13/group p<0.001, r2 = 0.55, linear regression). Data expressed as mean ± SE.
Mentions: To investigate whether MIC-1/GDF15 might contribute to the physiological regulation of energy homeostasis, the body weight of MIC-1−/− mice and syngeneic controls were monitored between the ages of 4 weeks to 1 year. Male MIC-1−/− mice were on average 6±0.6% heavier than male MIC-1+/+ control mice of the same age, and female MIC-1−/− mice weighed on average 10±0.7% more than female controls (Fig. 1A and 1B, male p = 0.04; female p = 0.01). For both male and female mice, the weight differences between genotypes increased significantly over time (Fig. 1C and 1D, female p<0.01; male p = 0.04).

Bottom Line: 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.

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, New South Wales, Australia.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus