Dysregulation of energy metabolism in obesity and its implications for cancer

• Published in: Journal of pediatric biochemistry Vol. 2; no. 3; pp. 133 - 142
• Main Authors: Battaglia, Lauren, DeStefano, Michael A., Hoffman, Andrew, Abali, Emine Ercikan
• Format: Journal Article
• Language: English
• Published: New York Georg Thieme Verlag KG 01.01.2012; Stuttgart
• Subjects: Review Article; Obesity; HIF-1; 2-deoxy-D-glucose; PI3K; mTOR; AMPK; metformin; cancer; leptin; energy metabolism
• ISSN: 1879-5390; 1879-5404
• DOI: 10.3233/JPB-2012-00055

Abstract In the past several decades obesity has become an increasingly problematic public health concern in developed countries. The strong correlation between high birth weights, obesity in adolescence and cancer is now evident. However, the molecular mechanism connecting obesity and cancer has yet to be elucidated. Here we review current literature investigating this relationship at both hormonal and biochemical levels. We also explore recent publications for novel cancer therapies that target pathways in which cancer manipulates host metabolism. The hormone leptin, which is upregulated in obese individuals, signals satiety and has been shown to play a role in signaling pathways promoting metastasis in a number of different cancers. Furthermore, leptin receptors are increased in some cancers and as a result these cells begin to utilize aerobic glycolysis for energy production as opposed to oxidative phosphorylation. Tumorigenic cells use alternative splicing to select for specific metabolic enzymes, which then serve as metabolic tools to promote tumor proliferation. A hypoxic environment can lead to the activation of AMP-activated protein kinase (AMPK), which in turn activates glycolytic machinery. It also upregulates transcription factors that promote tumor angiogenesis and allow sustained tumor growth. A more detailed understanding of metabolic aberrations due to obesity and their contribution to the onset of cancer is critical for the development of new therapies in the fight against both diseases.