title: The anorectic actions of the TGFβ cytokine MIC-1/GDF15 require an intact brainstem area postrema and nucleus of the solitary tract.
abstract: Macrophage inhibitory cytokine-1 (MIC-1/GDF15) modulates food intake and body weight under physiological and pathological conditions by acting on the hypothalamus and brainstem. When overexpressed in disease, such as in advanced cancer, elevated serum MIC-1/GDF15 levels lead to an anorexia/cachexia syndrome. To gain a better understanding of its actions in the brainstem we studied MIC-1/GDF15 induced neuronal activation identified by induction of Fos protein. Intraperitoneal injection of human MIC-1/GDF15 in mice activated brainstem neurons in the area postrema (AP) and the medial (m) portion of the nucleus of the solitary tract (NTS), which did not stain with tyrosine hydroxylase (TH). To determine the importance of these brainstem nuclei in the anorexigenic effect of MIC-1/GDF15, we ablated the AP alone or the AP and the NTS. The latter combined lesion completely reversed the anorexigenic effects of MIC-1/GDF15. Altogether, this study identified neurons in the AP and/or NTS, as being critical for the regulation of food intake and body weight by MIC-1/GDF15.
authors: St Vincent's Centre for Applied Medical Research, St Vincent's Hospital and University of New South Wales, Sydney, New South Wales, Australia.
authors: Vicky Wang-Wei
authors: VW
authors: Tsai
authors: St Vincent's Centre for Applied Medical Research, St Vincent's Hospital and University of New South Wales, Sydney, New South Wales, Australia.
authors: Rakesh
authors: R
authors: Manandhar
authors: Diabetes Research Unit, Novo Nordisk A/S, Maaloev, Denmark.
authors: Sebastian Beck
authors: SB
authors: Jørgensen
authors: St Vincent's Centre for Applied Medical Research, St Vincent's Hospital and University of New South Wales, Sydney, New South Wales, Australia.
authors: Ka Ki Michelle
authors: KK
authors: Lee-Ng
authors: St Vincent's Centre for Applied Medical Research, St Vincent's Hospital and University of New South Wales, Sydney, New South Wales, Australia.
authors: Hong Ping
authors: HP
authors: Zhang
authors: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia.
authors: Christopher Peter
authors: CP
authors: Marquis
authors: St Vincent's Centre for Applied Medical Research, St Vincent's Hospital and University of New South Wales, Sydney, New South Wales, Australia.
authors: Lele
authors: L
authors: Jiang
authors: St Vincent's Centre for Applied Medical Research, St Vincent's Hospital and University of New South Wales, Sydney, New South Wales, Australia.
authors: Yasmin
authors: Y
authors: Husaini
authors: Neuroscience Program, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
authors: Shu
authors: S
authors: Lin
authors: Neuroscience Program, Garvan Institute of Medical Research, Sydney, New South Wales, Australia; The Boden Institute of Obesity, Nutrition, Exercise & Eating Disorders, Sydney Medical School, The University of Sydney, New South Wales, Australia.
authors: Amanda
authors: A
authors: Sainsbury
authors: Laboratory of Neuronal Structure and Function, The Salk Institute for Biological Studies, La Jolla, California, United States of America.
authors: Paul E
authors: PE
authors: Sawchenko
authors: St Vincent's Centre for Applied Medical Research, St Vincent's Hospital and University of New South Wales, Sydney, New South Wales, Australia.
authors: David A
authors: DA
authors: Brown
authors: St Vincent's Centre for Applied Medical Research, St Vincent's Hospital and University of New South Wales, Sydney, New South Wales, Australia.
authors: Samuel N
authors: SN
authors: Breit
mesh_terms: D000818:Animals; D000855:Anorexia / Q000139:chemically induced; D001067:Appetite Depressants / Q000008:administration & dosage / Q000494:pharmacology*; D031608:Area Postrema / Q000187:drug effects* / Q000502:physiology*; D055436:Growth Differentiation Factor 15 / Q000008:administration & dosage / Q000494:pharmacology*; D057967:Infusions, Intraventricular; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D017552:Solitary Nucleus / Q000187:drug effects* / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D015431:Weight Loss / Q000187:drug effects
chemical_list: D001067:Appetite Depressants; D055436:Growth Differentiation Factor 15; D016760:Proto-Oncogene Proteins c-fos; D014446:Tyrosine 3-Monooxygenase