Pathophysiology of anorexia in the cancer cachexia syndrome

Abstract

Anorexia is commonly present in persons with cancer and a major component of cancer cachexia. There are multiple causes of anorexia in cancer. Peripherally, these can be due to (i) substances released from or by the tumour, e.g. pro-inflammatory cytokines, lactate, and parathormone-related peptide; (ii) tumours causing dysphagia or altering gut function; (iii) tumours altering nutrients, e.g. zinc deficiency; (iv) tumours causing hypoxia; (v) increased peripheral tryptophan leading to increased central serotonin; or (vi) alterations of release of peripheral hormones that alter feeding, e.g. peptide tyrosine tyrosine and ghrelin. Central effects include depression and pain, decreasing the desire to eat. Within the central nervous system, tumours create multiple alterations in neurotransmitters, neuropeptides, and prostaglandins that modulate feeding. Many of these neurotransmitters appear to produce their anorectic effects through the adenosine monophosphate kinase/methylmalonyl coenzyme A/fatty acid system in the hypothalamus. Dynamin is a guanosine triphosphatase that is responsible for internalization of melanocortin 4 receptors and prostaglandin receptors. Dynamin is up-regulated in a mouse model of cancer anorexia. A number of drugs, e.g. megestrol acetate, cannabinoids, and ghrelin agonists, have been shown to have some ability to be orexigenic in cancer patients.

Establishment and characterization of a novel murine model of pancreatic cancer cachexia

“…A large body of evidence demonstrates that the hypothalamus is a critical driver of cachexia, transducing systemic inflammatory messages stemming from acute and chronic disease processes into a local and paracrine inflammatory response in the central nervous system 23, 24, 25. Consistent with this evidence, KPC induces an array of genes responsive to inflammatory stimuli in the hypothalamus.…”

Personalized polyunsaturated fatty acids as a potential adjunctive treatment for anorexia nervosa

“…Inflammation is thought to be a primary cause of loss of appetite (anorexia) in cancer cachexia, a syndrome characterized by systemic inflammation, negative protein and energy balance, and progressive loss of adipose tissue and skeletal muscle mass [68,74]. Various studies showed that n-3 PUFA supplementation improves anorexia via an anti-inflammatory effect, evident by inhibition of cytokine production and by promoting the release of hypothalamic orexigenic peptides and neurotransmitters to increase appetite [75].…”

Defining Undernutrition (Malnutrition) in Older Persons

“…Cachexia is defined as a loss of lean mass due to inflammatory cytokines (55,56). It also has anorexia, anemia, and low albumin (57). Persons with cachexia have a loss of muscle out of proportion to fat loss.…”