title: TGF-b superfamily cytokine MIC-1/GDF15 is a physiological appetite and body weight regulator.
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.
authors.affiliation: St Vincent's Centre for Applied Medical Research, St Vincent's Hospital and University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Vicky Wang-Wei
authors.initials: VW
authors.lastname: Tsai
authors.forename: Laurence
authors.initials: L
authors.lastname: Macia
authors.forename: Heiko
authors.initials: H
authors.lastname: Johnen
authors.forename: Tamara
authors.initials: T
authors.lastname: Kuffner
authors.forename: Rakesh
authors.initials: R
authors.lastname: Manadhar
authors.forename: Sebastian Beck
authors.initials: SB
authors.lastname: Jørgensen
authors.forename: Ka Ki Michelle
authors.initials: KK
authors.lastname: Lee-Ng
authors.forename: Hong Ping
authors.initials: HP
authors.lastname: Zhang
authors.forename: Liyun
authors.initials: L
authors.lastname: Wu
authors.forename: Christopher Peter
authors.initials: CP
authors.lastname: Marquis
authors.forename: Lele
authors.initials: L
authors.lastname: Jiang
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Husaini
authors.forename: Shu
authors.initials: S
authors.lastname: Lin
authors.forename: Herbert
authors.initials: H
authors.lastname: Herzog
authors.forename: David A
authors.initials: DA
authors.lastname: Brown
authors.forename: Amanda
authors.initials: A
authors.lastname: Sainsbury
authors.forename: Samuel N
authors.initials: SN
authors.lastname: Breit
mesh_terms: D000273:Adipose Tissue / Q000254:growth & development; D000818:Animals; D001066:Appetite / Q000235:genetics* / Q000502:physiology; D001835:Body Weight / Q000235:genetics* / Q000502:physiology; D004435:Eating; D004734:Energy Metabolism / Q000235:genetics; D005260:Female; D005838:Genotype; D055436:Growth Differentiation Factor 15 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009929:Organ Size; D012737:Sex Factors; D015398:Signal Transduction; D015430:Weight Gain / Q000235:genetics
chemical_list: D055436:Growth Differentiation Factor 15