Carnitine palmitoyltransferase II activity is decreased in liver mitochondria of cachectic rats bearing the Walker 256 carcinosarcoma: Effect of indomethacin treatment

Seelaender, M.C.L.; Curi, Rui; Colquhoun, Alison; Williams, John F.; Zammitt, Victor A.

doi:10.1080/15216549800201202

Cited by 32 publications

(59 citation statements)

References 21 publications

(28 reference statements)

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“…Steatosis 26,30 and reductions in fatty acid oxidation/oxidative capacity 25,27,59 in the liver have been reported in the Walker 256 carcinosarcoma cachexia model when weight loss was substantial. In our study of early cachexia, markers of fatty acid oxidation were increased in liver and measurements of hepatic total lipids were not different among groups.…”

Section: Discussionmentioning

confidence: 99%

Adipose tissue lipolysis and energy metabolism in early cancer cachexia in mice

Kliewer

Tian

et al. 2014

Cancer Biology & Therapy

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Keywords: colon-26 adenocarcinoma, early cachexia, energy expenditure, lipid metabolism, lipolysis, thermogenesis Abbreviations: eWAT, epididymal white adipose tissue; iWAT, inguinal white adipose tissue; iBAT, interscapular brown adipose tissue; PKA, protein kinase A; ATGL, adipose triglyceride lipase; HSL, hormone sensitive lipase; UCP, uncoupling protein; PPAR, peroxisome proliferator activated receptor; PGC, peroxisome proliferator activated receptor gamma coactivator; CPT, carnitine palmitoyltransferase; DIO, iodothyronine deiodinase; MuRF, muscle ring finger protein; COX, cytochrome c oxidase subunits; GYK, glycerokinase; PRDM, PR domain zinc finger protein; ACOX, acyl CoA oxidase; CRP, C-reactive protein; LPL, lipoprotein lipase; H&E, hematoxylin and eosin; TEE, total energy expenditure; RER, respiratory exchange ratio.Cancer cachexia is a progressive metabolic disorder that results in depletion of adipose tissue and skeletal muscle. A growing body of literature suggests that maintaining adipose tissue mass in cachexia may improve quality-of-life and survival outcomes. Studies of lipid metabolism in cachexia, however, have generally focused on later stages of the disorder when severe loss of adipose tissue has already occurred. Here, we investigated lipid metabolism in adipose, liver and muscle tissues during early stage cachexia -before severe fat loss -in the colon-26 murine model of cachexia. White adipose tissue mass in cachectic mice was moderately reduced (34-42%) and weight loss was less than 10% of initial body weight in this study of early cachexia. In white adipose depots of cachectic mice, we found evidence of enhanced protein kinase A -activated lipolysis which coincided with elevated total energy expenditure and increased expression of markers of brown (but not white) adipose tissue thermogenesis and the acute phase response. Total lipids in liver and muscle were unchanged in early cachexia while markers of fatty oxidation were increased. Many of these initial metabolic responses contrast with reports of lipid metabolism in later stages of cachexia. Our observations suggest intervention studies to preserve fat mass in cachexia should be tailored to the stage of cachexia. Our observations also highlight a need for studies that delineate the contribution of cachexia stage and animal model to altered lipid metabolism in cancer cachexia and identify those that most closely mimic the human condition.

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Section: Discussionmentioning

confidence: 99%

Adipose tissue lipolysis and energy metabolism in early cancer cachexia in mice

Kliewer

Tian

et al. 2014

Cancer Biology & Therapy

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“…That is to say, FAO in liver diseases is mainly limited by CPT 2. Seelaender et al have also found that CPT 2 activity shrank in rats bearing the Walker 256 carcinosarcoma and the expression of CPT 2 may be affected by a prostaglandin, PGE(2) [48].…”

Section: Alterations Of Serum Acylcarnitine Level Among Hcc and Cldmentioning

confidence: 99%

Serum metabolomics reveals the deregulation of fatty acids metabolism in hepatocellular carcinoma and chronic liver diseases

et al. 2012

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Patients with chronic liver diseases (CLD) including chronic hepatitis B and hepatic cirrhosis (CIR) are the major high-risk population of hepatocellular carcinoma (HCC). The differential diagnosis between CLD and HCC is a challenge. This work aims to study the related metabolic deregulations in HCC and CLD to promote the discovery of the differential metabolites for distinguishing the different liver diseases. Serum metabolic profiling analysis from patients with CLD and HCC was performed using a liquid chromatography-mass spectrometry system. The acquired large amount of metabolic information was processed with the random forest-recursive feature elimination method to discover important metabolic changes. It was found that long-chain acylcarnitines accumulated, whereas free carnitine, medium and short-chain acylcarnitines decreased with the severity of the non-malignant liver diseases, accompanied with corresponding alterations of enzyme activities. However, the general changing extent was smaller in HCC than in CIR, possibly due to the special energy-consumption mechanism of tumor cells. These observations may help to understand the mechanism of HCC occurrence and progression on the metabolic level and provide information for the identification of early and differential metabolic markers for HCC.

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“…Walker 256 tumour cells (2!10 7 cells) were injected s.c. into the right flank of the animals (Seelaender et al 1998). Control rats received saline injections on the same day of tumour inoculation.…”

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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Carnitine palmitoyltransferase II activity is decreased in liver mitochondria of cachectic rats bearing the Walker 256 carcinosarcoma: Effect of indomethacin treatment

Cited by 32 publications

References 21 publications

Adipose tissue lipolysis and energy metabolism in early cancer cachexia in mice

Adipose tissue lipolysis and energy metabolism in early cancer cachexia in mice

Serum metabolomics reveals the deregulation of fatty acids metabolism in hepatocellular carcinoma and chronic liver diseases

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

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