CNTF: a target therapeutic for obesity-related metabolic disease?
Obesity and type 2 diabetes are the most prevalent metabolic diseases in the western world. Alarmingly, the cluster of pathologies characteristic of obesity-induced disease have started to emerge in children, a phenomenon that up until a decade ago was inconceivable. Hence, the development of new strategies to treat 'metabolic disease' is most warranted. Growing evidence suggests that during type 2 diabetes, a state of chronic low-grade inflammation exists in metabolically active tissues such as the liver, adipose tissue and skeletal muscle. This inflammation is often secondary to lipid accumulation in insulin-responsive tissues. Recent studies have focused on the therapeutic potential of ciliary neurotrophic factor (CNTF). CNTF is a pluripotent neurocytokine and, has shown promise as a potential anti-obesogenic therapy. CNTF acts both centrally and peripherally, mimics the biological actions of leptin while overcoming "leptin resistance", remains effective even after termination of therapy if administered centrally, and appears to reduce inflammatory signaling cascades associated with lipid accumulation in liver and skeletal muscle. The advantages and disadvantages of CNTF as a therapeutic strategy to alleviate obesity-associated diseases will be highlighted in this review.
Matthews
Vance B
VB
Division of Diabetes and Metabolism, Cellular and Molecular Metabolism Laboratory, Baker Heart Research Institute, P.O. Box 6492, St Kilda Road Central, VIC 8008, Australia.
Febbraio
Mark A
MA
D001921:Brain / Q000378:metabolism; D020934:Ciliary Neurotrophic Factor / Q000378:metabolism*; D002986:Clinical Trials as Topic; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D020738:Leptin / Q000378:metabolism; D009765:Obesity / Q000503:physiopathology / Q000628:therapy; D020801:Receptor, Ciliary Neurotrophic Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D015431:Weight Loss
D020934:Ciliary Neurotrophic Factor; D020738:Leptin; D020801:Receptor, Ciliary Neurotrophic Factor