Animal models of the cancer anorexia–cachexia syndrome

Bennani-Baiti, Nabila; Walsh, Declan

doi:10.1007/s00520-010-0972-0

Cited by 80 publications

(63 citation statements)

References 69 publications

(65 reference statements)

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“…LPS administration induced anorexia, which is in line with previous studies (Gautron et al 2005, Ogimoto et al 2006. LPS administration stimulates the release of pro-inflammatory cytokines such as IL1, TNFa, IL6, and so on (O'Reilly et al 1988, Plata-Salaman 1999, Wong & Pinkney 2004, Bennani-Baiti & Walsh 2011. These cytokines may be associated with the induction of anorexia; however, hypothalamic inflammatory signals, rather than peripheral, have been identified as the major causes of LPS-induced anorexia (Laye et al 2000, Plata-Salaman 2000, Wisse et al 2007).…”

Section: Nfkb Activation In the Hypothalamus Is Involved In Lps-inducsupporting

confidence: 87%

A central role for the mammalian target of rapamycin in LPS-induced anorexia in mice

Yue

Wang

et al. 2014

Journal of Endocrinology

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Bacterial lipopolysaccharide (LPS), also known as endotoxin, induces profound anorexia. However, the LPS-provoked pro-inflammatory signaling cascades and the neural mechanisms underlying the development of anorexia are not clear. Mammalian target of rapamycin (mTOR) is a key regulator of metabolism, cell growth, and protein synthesis. This study aimed to determine whether the mTOR pathway is involved in LPS-induced anorexia. Effects of LPS on hypothalamic gene/protein expression in mice were measured by RT-PCR or western blotting analysis. To determine whether inhibition of mTOR signaling could attenuate LPS-induced anorexia, we administered an i.c.v. injection of rapamycin, an mTOR inhibitor, on LPS-treated male mice. In this study, we showed that LPS stimulates the mTOR signaling pathway through the enhanced phosphorylation of mTOR Ser2448 and p70S6K Thr389 . We also showed that LPS administration increased the phosphorylation of FOXO1 Ser256 , the p65 subunit of nuclear factor kappa B (P!0.05), and FOXO1/3a Thr24/32 (P!0.01). Blocking the mTOR pathway significantly attenuated the LPS-induced anorexia by decreasing the phosphorylation of p70S6K Thr389 , FOXO1 Ser256 , and FOXO1/3a Thr24/32 . These results suggest promising approaches for the prevention and treatment of LPS-induced anorexia.

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Section: Nfkb Activation In the Hypothalamus Is Involved In Lps-inducsupporting

confidence: 87%

A central role for the mammalian target of rapamycin in LPS-induced anorexia in mice

Yue

Wang

et al. 2014

Journal of Endocrinology

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“…Control rats received saline injections on the same day of tumour inoculation. Cachectic syndrome is observed in rats bearing Walker 256 tumour cells after 10-15 days (Bennani-Baiti & Walsh 2011). To evaluate the development of cancer cachexia, the experiments were carried out in the time course study, when the rats were killed on days 4, 7, 10 or 14 post-injection (seven to ten animals on each time point) by decapitation after 12 h fasting.…”

Section: Animalsmentioning

confidence: 99%

Heterogeneous time-dependent response of adipose tissue during the development of cancer cachexia

Batista¹,

Neves²,

Peres³

et al. 2012

Journal of Endocrinology

100

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Cancer cachexia induces loss of fat mass that accounts for a large part of the dramatic weight loss observed both in humans and in animal models; however, the literature does not provide consistent information regarding the set point of weight loss and how the different visceral adipose tissue depots contribute to this symptom. To evaluate that, 8-week-old male Wistar rats were subcutaneously inoculated with 1 ml (2!10 7 ) of tumour cells (Walker 256). Samples of different visceral white adipose tissue (WAT) depots were collected at days 0, 4, 7 and 14 and stored at K80 8C (seven to ten animals/each day per group). Mesenteric and retroperitoneal depot mass was decreased to the greatest extent on day 14 compared with day 0. Gene and protein expression of PPARg2 (PPARG) fell significantly following tumour implantation in all three adipose tissue depots while C/EBPa (CEBPA) and SREBP-1c (SREBF1) expression decreased over time only in epididymal and retroperitoneal depots. Decreased adipogenic gene expression and morphological disruption of visceral WAT are further supported by the dramatic reduction in mRNA and protein levels of perilipin. Classical markers of inflammation and macrophage infiltration (f4/80, CD68 and MIF-1a) in WAT were significantly increased in the later stage of cachexia (although showing a incremental pattern along the course of cachexia) and presented a depot-specific regulation. These results indicate that impairment in the lipid-storing function of adipose tissue occurs at different times and that the mesenteric adipose tissue is more resistant to the 'fat-reducing effect' than the other visceral depots during cancer cachexia progression.

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“…However, there are many limitations when extrapolating such models to the human situation, including the more acute versus chronic timescales of tumor growth and development of muscle wasting (8). Because of the invasive nature of clinical protocols to date, there are few studies of skeletal muscle protein metabolism in human cancer cachexia and these have demonstrated either markedly reduced (9) or unchanged (2) fractional synthetic rate (FSR) when compared with controls.…”

Section: Introductionmentioning

confidence: 99%

Habitual Myofibrillar Protein Synthesis Is Normal in Patients with Upper GI Cancer Cachexia

MacDonald

Johns

Stephens

et al. 2015

Clinical Cancer Research

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Purpose: Skeletal muscle wasting and weight loss are characteristic features of cancer cachexia and contribute to impaired function, increased morbidity, and poor tolerance of chemotherapy. This study used a novel technique to measure habitual myofibrillar protein synthesis in patients with cancer compared with healthy controls.Experimental design: An oral heavy water (87.5 g deuterium oxide) tracer was administered as a single dose. Serum samples were taken over the subsequent week followed by a quadriceps muscle biopsy. Deuterium enrichment was measured in body water, serum alanine, and alanine in the myofibrillar component of muscle using gas chromatography-pyrolysisisotope ratio mass spectrometry and the protein synthesis rate calculated from the rate of tracer incorporation. Net change in muscle mass over the preceding 3 months was calculated from serial CT scans and allowed estimation of protein breakdown.Results: Seven healthy volunteers, 6 weight-stable, and 7 weight-losing (!5% weight loss) patients undergoing surgery for upper gastrointestinal cancer were recruited. Serial CT scans were available in 10 patients, who lost skeletal muscle mass preoperatively at a rate of 5.6%/100 days. Myofibrillar protein fractional synthetic rate was 0.058%, 0.061%, and 0.073%/hour in controls, weight-stable, and weight-losing patients, respectively. Weightlosing patients had higher synthetic rates than controls (P ¼ 0.03).Conclusion: Contrary to previous studies, there was no evidence of suppression of myofibrillar protein synthesis in patients with cancer cachexia. Our finding implies a small increase in muscle breakdown may account for muscle wasting.

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Animal models of the cancer anorexia–cachexia syndrome

Cited by 80 publications

References 69 publications

A central role for the mammalian target of rapamycin in LPS-induced anorexia in mice

A central role for the mammalian target of rapamycin in LPS-induced anorexia in mice

Heterogeneous time-dependent response of adipose tissue during the development of cancer cachexia

Habitual Myofibrillar Protein Synthesis Is Normal in Patients with Upper GI Cancer Cachexia

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