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 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.
authors.affiliation: St Vincent's Centre for Applied Medical Research, St Vincent's Hospital and University of New South Wales, Sydney, NSW, Australia.
authors.forename: Vicky Wang-Wei
authors.initials: VW
authors.lastname: Tsai
authors.affiliation: Centre for Immunology and Inflammation, School of Biomedical Sciences, Monash University, Clayton, VIC, Australia.
authors.forename: Laurence
authors.initials: L
authors.lastname: Macia
authors.affiliation: Discipline of Medicine University of Adelaide, Adelaide, SA, Australia.
authors.forename: Christine
authors.initials: C
authors.lastname: Feinle-Bisset
authors.affiliation: St Vincent's Centre for Applied Medical Research, St Vincent's Hospital and University of New South Wales, Sydney, NSW, Australia.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Manandhar
authors.affiliation: Department of Nutrition, Exercise and Sports, Faculty of Science. University of Copenhagen, Frederiksberg C, Copenhagen, Denmark.
authors.forename: Arne
authors.initials: A
authors.lastname: Astrup
authors.affiliation: Department of Nutrition, Exercise and Sports, Faculty of Science. University of Copenhagen, Frederiksberg C, Copenhagen, Denmark.
authors.forename: Anne
authors.initials: A
authors.lastname: Raben
authors.affiliation: Department of Nutrition, Exercise and Sports, Faculty of Science. University of Copenhagen, Frederiksberg C, Copenhagen, Denmark.
authors.forename: Janne Kunchel
authors.initials: JK
authors.lastname: Lorenzen
authors.affiliation: Department of Medicine, Unit of Gastroenterology and Hepatology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Schmidt
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Wiklund
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Pedersen
authors.affiliation: Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney, NSW, Australia.
authors.forename: Lesley
authors.initials: L
authors.lastname: Campbell
authors.affiliation: Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney, NSW, Australia.
authors.forename: Adamandia
authors.initials: A
authors.lastname: Kriketos
authors.affiliation: Department of Medicine & Department of Pharmacology & Pharmacy, University of Hong Kong, Hong Kong, China.
authors.forename: Aimin
authors.initials: A
authors.lastname: Xu
authors.affiliation: Department of Medicine & Department of Pharmacology & Pharmacy, University of Hong Kong, Hong Kong, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Pengcheng
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Diabetes Institute, Shanghai Clinical Center of Diabetes, Shanghai, China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Jia
authors.affiliation: School of Physics, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Paul M G
authors.initials: PM
authors.lastname: Curmi
authors.affiliation: School of Mathematics and Statistics, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Christopher N
authors.initials: CN
authors.lastname: Angstmann
authors.affiliation: St Vincent's Centre for Applied Medical Research, St Vincent's Hospital and University of New South Wales, Sydney, NSW, Australia.
authors.forename: Ka Ki Michelle
authors.initials: KK
authors.lastname: Lee-Ng
authors.affiliation: St Vincent's Centre for Applied Medical Research, St Vincent's Hospital and University of New South Wales, Sydney, NSW, Australia.
authors.forename: Hong Ping
authors.initials: HP
authors.lastname: Zhang
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Marquis
authors.affiliation: St Vincent's Centre for Applied Medical Research, St Vincent's Hospital and University of New South Wales, Sydney, NSW, Australia.
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Husaini
authors.affiliation: Clinical Research Center, Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Beglinger
authors.affiliation: Neuroscience Division, Garvan Institute of Medical Research, Sydney, NSW, Australia.
authors.forename: Shu
authors.initials: S
authors.lastname: Lin
authors.affiliation: Neuroscience Division, Garvan Institute of Medical Research, Sydney, NSW, Australia.
authors.forename: Herbert
authors.initials: H
authors.lastname: Herzog
authors.affiliation: St Vincent's Centre for Applied Medical Research, St Vincent's Hospital and University of New South Wales, Sydney, NSW, Australia.
authors.forename: David A
authors.initials: DA
authors.lastname: Brown
authors.affiliation: The Boden Institute of Obesity, Nutrition, Exercise & Eating Disorders, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
authors.forename: Amanda
authors.initials: A
authors.lastname: Sainsbury
authors.affiliation: St Vincent's Centre for Applied Medical Research, St Vincent's Hospital and University of New South Wales, Sydney, NSW, Australia.
authors.forename: Samuel N
authors.initials: SN
authors.lastname: Breit
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D002766:Cholecystokinin / Q000494:pharmacology; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period / Q000502:physiology*; D012527:Satiation / Q000187:drug effects / Q000502:physiology*; D014427:Twins; D055815:Young Adult
chemical_list: C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D052216:Glucagon-Like Peptide 1; D002766:Cholecystokinin