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The pathogenesis of cancer anorexia is multifactorial and associated with disturbances of the central physiological mechanisms controlling food intake. However, the neurochemical mechanisms responsible for cancer-induced anorexia are unclear. Here we show that chronic infusion of 5-amino-4imidazolecarboxamide-riboside into the third cerebral ventricle and a chronic peripheral injection of 2 deoxy-d-glucose promotes hypothalamic AMP-activated protein kinase (AMPK) activation, increases food intake, and prolongs the survival of anorexic tumor-bearing (TB) rats. In parallel, the pharmacological activation of hypothalamic AMPK in TB animals markedly reduced the hypothalamic production of inducible nitric oxide synthase, IL-1beta, and TNF-alpha and modulated the expression of proopiomelanocortin, a hypothalamic neuropeptide that is involved in the control of energy homeostasis. Furthermore, the daily oral and intracerebroventricular treatment with biguanide antidiabetic drug metformin also induced AMPK phosphorylation in the central nervous system and increased food intake and life span in anorexic TB rats. Collectively, the findings of this study suggest that hypothalamic AMPK activation reverses cancer anorexia by inhibiting the production of proinflammatory molecules and controlling the neuropeptide expression in the hypothalamus, reflecting in a prolonged life span in TB rats. Thus, our data indicate that hypothalamic AMPK activation presents an attractive opportunity for the treatment of cancer-induced anorexia.
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http://dx.doi.org/10.1210/en.2007-0381 | DOI Listing |
Biochim Biophys Acta Rev Cancer
November 2024
Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China; Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310018, China. Electronic address:
Tumor cachexia is a multifactorial syndrome characterized by systemic dysfunction, including anorexia and severe weight loss that is resistant to standard nutritional interventions. It is estimated that approximately 20 % of cancer patients succumb to cachexia in the later stages of their disease. Thus, understanding its pathogenesis is vital for improving therapeutic outcomes.
View Article and Find Full Text PDFLife Sci
December 2024
Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India. Electronic address:
Aims: This review aims to elucidate the bidirectional relationship between heart failure and cancer by identifying their common and reciprocal risk factors. It seeks to provide a comprehensive understanding of the mechanistic interactions between these two conditions, supported by evidence from preclinical and clinical investigations.
Materials And Methods: A thorough review of peer-reviewed articles was conducted to identify all possible interactions between cancer and heart failure.
Integr Med Res
March 2024
Graduate School of Bioindustrial Engineering, Yonsei University, Seoul, Republic of Korea.
Background: Cancer cachexia-characterized by anorexia, body weight loss, skeletal muscle atrophy, and fat loss-affects nearly 80% of cancer patients and accounts for 20% of cancer deaths. , known as Java turmeric, and its active compound xanthorrhizol (XAN) exhibit anticancer, anti-inflammatory, and antioxidant properties. However, the ameliorative effects of extract (CXE) and XAN on cancer-associated adipose atrophy remain unexplored.
View Article and Find Full Text PDFJ Cachexia Sarcopenia Muscle
December 2022
Nutritional Biology, Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
Background: Cachexia-anorexia syndrome is a complex metabolic condition characterized by skeletal muscle wasting, reduced food intake and prominent involvement of systemic and central inflammation. Here, the gut barrier function was investigated in pancreatic cancer-induced cachexia mouse models by relating intestinal permeability to the degree of cachexia. We further investigated the involvement of the gut-brain axis and the crosstalk between tumour, gut and hypothalamus in vitro.
View Article and Find Full Text PDFCells
August 2022
Department of Neurosciences, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy.
Cachexia is a metabolic syndrome consisting of massive loss of muscle mass and function that has a severe impact on the quality of life and survival of cancer patients. Up to 20% of lung cancer patients and up to 80% of pancreatic cancer patients are diagnosed with cachexia, leading to death in 20% of them. The main drivers of cachexia are cytokines such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), macrophage inhibitory cytokine 1 (MIC-1/GDF15) and transforming growth factor-beta (TGF-β).
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