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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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Related in: MedlinePlus

Lack of MIC-1 signaling alters the regulation of body fat depots. (A) Whole body lean mass and (B) fat mass was determined by dual energy X-ray absorptiometry (DXA) in 15 mice per group at 12–14 weeks of age. Female MIC-1−/− mice had lower lean mass relative to control mice (p<0.01, n = 15/group, t-test), Both male and female MIC-1−/− mice had significantly higher fat depot mases compared to synergic control (male p<0.01, female p = 0.04, n = 15/group, t-test). Mass of individual white adipose tissue depots were measured in (C) male and (D) female mice (n = 9/group) aged between 14–16 weeks. Fat masses, namely inguinal, epididymal (Epididy), mesenteric (Mesent), retroperitoneal (Retrop), and total white adipose tissue (WATt) were normalized to body weight. In both male and female MIC-1−/− mice, WATt depots were significantly higher than the synergic control (male p<0.01, female p = 0.02, n = 9/group, t-test). Data are means ± SE. Significance indicated as () for p<0.05 or () for p<0.01.
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pone-0055174-g002: Lack of MIC-1 signaling alters the regulation of body fat depots. (A) Whole body lean mass and (B) fat mass was determined by dual energy X-ray absorptiometry (DXA) in 15 mice per group at 12–14 weeks of age. Female MIC-1−/− mice had lower lean mass relative to control mice (p<0.01, n = 15/group, t-test), Both male and female MIC-1−/− mice had significantly higher fat depot mases compared to synergic control (male p<0.01, female p = 0.04, n = 15/group, t-test). Mass of individual white adipose tissue depots were measured in (C) male and (D) female mice (n = 9/group) aged between 14–16 weeks. Fat masses, namely inguinal, epididymal (Epididy), mesenteric (Mesent), retroperitoneal (Retrop), and total white adipose tissue (WATt) were normalized to body weight. In both male and female MIC-1−/− mice, WATt depots were significantly higher than the synergic control (male p<0.01, female p = 0.02, n = 9/group, t-test). Data are means ± SE. Significance indicated as () for p<0.05 or () for p<0.01.

Mentions: To understand what might have contributed to the increased body weight in MIC-1−/− mice, whole body lean and fat mass were determined by dual energy X-ray absorptiometry (DXA). Whilst male MIC-1−/− mice show a similar lean body mass to age and sex matched controls, female MIC-1−/− mice had a significantly lower lean body mass than age and sex matched MIC-1+/+ mice (Fig. 2A, male p = 0.21; female p<0.01). Both male and female MIC-1−/− mice had a significantly higher total fat mass relative to the sex matched MIC-1+/+ mice (Fig. 2B, male p<0.01; female 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)

Lack of MIC-1 signaling alters the regulation of body fat depots. (A) Whole body lean mass and (B) fat mass was determined by dual energy X-ray absorptiometry (DXA) in 15 mice per group at 12–14 weeks of age. Female MIC-1−/− mice had lower lean mass relative to control mice (p<0.01, n = 15/group, t-test), Both male and female MIC-1−/− mice had significantly higher fat depot mases compared to synergic control (male p<0.01, female p = 0.04, n = 15/group, t-test). Mass of individual white adipose tissue depots were measured in (C) male and (D) female mice (n = 9/group) aged between 14–16 weeks. Fat masses, namely inguinal, epididymal (Epididy), mesenteric (Mesent), retroperitoneal (Retrop), and total white adipose tissue (WATt) were normalized to body weight. In both male and female MIC-1−/− mice, WATt depots were significantly higher than the synergic control (male p<0.01, female p = 0.02, n = 9/group, t-test). Data are means ± SE. Significance indicated as () for p<0.05 or () for p<0.01.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3585300&req=5

pone-0055174-g002: Lack of MIC-1 signaling alters the regulation of body fat depots. (A) Whole body lean mass and (B) fat mass was determined by dual energy X-ray absorptiometry (DXA) in 15 mice per group at 12–14 weeks of age. Female MIC-1−/− mice had lower lean mass relative to control mice (p<0.01, n = 15/group, t-test), Both male and female MIC-1−/− mice had significantly higher fat depot mases compared to synergic control (male p<0.01, female p = 0.04, n = 15/group, t-test). Mass of individual white adipose tissue depots were measured in (C) male and (D) female mice (n = 9/group) aged between 14–16 weeks. Fat masses, namely inguinal, epididymal (Epididy), mesenteric (Mesent), retroperitoneal (Retrop), and total white adipose tissue (WATt) were normalized to body weight. In both male and female MIC-1−/− mice, WATt depots were significantly higher than the synergic control (male p<0.01, female p = 0.02, n = 9/group, t-test). Data are means ± SE. Significance indicated as () for p<0.05 or () for p<0.01.
Mentions: To understand what might have contributed to the increased body weight in MIC-1−/− mice, whole body lean and fat mass were determined by dual energy X-ray absorptiometry (DXA). Whilst male MIC-1−/− mice show a similar lean body mass to age and sex matched controls, female MIC-1−/− mice had a significantly lower lean body mass than age and sex matched MIC-1+/+ mice (Fig. 2A, male p = 0.21; female p<0.01). Both male and female MIC-1−/− mice had a significantly higher total fat mass relative to the sex matched MIC-1+/+ mice (Fig. 2B, male p<0.01; female 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