Pathophysiology of anorexia in the cancer cachexia syndrome

Ezeoke, Chukwuemeka Charles; Morley, John E.

doi:10.1002/jcsm.12059

Cited by 166 publications

(131 citation statements)

References 211 publications

(364 reference statements)

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“…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.…”

Section: Resultsmentioning

confidence: 79%

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

Michaelis

Zhu

Burfeind

et al. 2017

J cachexia sarcopenia muscle

110

161

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BackgroundCachexia is a complex metabolic and behavioural syndrome lacking effective therapies. Pancreatic ductal adenocarcinoma (PDAC) is one of the most important conditions associated with cachexia, with >80% of PDAC patients suffering from the condition. To establish the cardinal features of a murine model of PDAC‐associated cachexia, we characterized the effects of implanting a pancreatic tumour cell line from a syngeneic C57BL/6 KRASG12D P53R172H Pdx‐Cre+/+ (KPC) mouse.MethodsMale and female C57BL/6 mice were inoculated subcutaneously, intraperitoneally, or orthotopically with KPC tumour cells. We performed rigorous phenotypic, metabolic, and behavioural analysis of animals over the course of tumour development.ResultsAll routes of administration produced rapidly growing tumours histologically consistent with moderate to poorly differentiated PDAC. The phenotype of this model was dependent on route of administration, with orthotopic and intraperitoneal implantation inducing more severe cachexia than subcutaneous implantation. KPC tumour growth decreased food intake, decreased adiposity and lean body mass, and decreased locomotor activity. Muscle catabolism was observed in both skeletal and cardiac muscles, but the dominant catabolic pathway differed between these tissues. The wasting syndrome in this model was accompanied by hypothalamic inflammation, progressively decreasing brown and white adipose tissue uncoupling protein 1 (Ucp1) expression, and increased peripheral inflammation. Haematological and endocrine abnormalities included neutrophil‐dominant leukocytosis and anaemia, and decreased serum testosterone.ConclusionsSyngeneic KPC allografts are a robust model for studying cachexia, which recapitulate key features of the PDAC disease process and induce a wide array of cachexia manifestations. This model is therefore ideally suited for future studies exploring the physiological systems involved in cachexia and for preclinical studies of novel therapies.

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Section: Resultsmentioning

confidence: 79%

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

Michaelis

Zhu

Burfeind

et al. 2017

J cachexia sarcopenia muscle

110

161

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“…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].…”

Section: Discussionmentioning

confidence: 99%

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

Shih

Morisseau

et al. 2017

Prostaglandins & Other Lipid Mediators

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Anorexia nervosa (AN) is a complex psychiatric disorder with high morbidity and mortality rates. While many individuals make full recoveries, up to a third of patients develop a chronic, treatment-resistant form of the illness that leads to a premature death in 15–20% of those affected. There have been few advances in treatment, both in terms of psychological or pharmacologic treatment over the last 30 years. Food aversion is commonly cited by patients with AN as a barrier to normalizing eating and weight. Our group has a keen interest in examining factors that might allow this to be addressed, thus improving treatment outcomes through personalized dietary plans or nutritional supplementation related to underlying genetic status. We demonstrated that polyunsaturated fatty acids (PUFAs)-derived bioactive lipids (eicosanoids) are implicated in not only the risk of AN, but also with its comorbid psychopathology. Of interest, the differential postprandial omega 6-derived eicosanoid shift observed in AN highlights the possibility that the metabolism of PUFAs is an important mechanism underlying the profound food version, contributing to pathological food restriction in AN. A concise knowledge of the relationships among PUFAs, eicosanoids, and AN clinical course and psychopathology could be the key to developing personalized nutritional rehabilitative treatments for those suffering from AN. This paper provides a comprehensive overview of the literature on PUFAs in AN. We also selectively reviewed the clinical benefits PUFA treatments exert in other psychiatric diseases, on weight and appetite regulation, and for resolution of inflammation, all of which are relevant in the disease course and outcome of AN. We propose that personalized PUFA formulation be developed and tested as a novel adjunctive treatment for patients with AN. We hypothesize that with personalized PUFA formulation, food aversion and anxiety about eating will decrease while mood, dietary behavior, and weight restoration will improve in AN, leading to improvements in the overall treatment outcome.

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“…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.…”

Section: Figure 2 Mechanisms By Which Dysphagia Causes Undernutritionmentioning

confidence: 99%

Defining Undernutrition (Malnutrition) in Older Persons

Morley

2018

The Journal of nutrition, health and aging

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Pathophysiology of anorexia in the cancer cachexia syndrome

Cited by 166 publications

References 211 publications

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

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

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

Defining Undernutrition (Malnutrition) in Older Persons

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