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L-Carnitine Ameliorates Cancer Cachexia in Mice Partly via the Carnitine Palmitoyltransferase-Associated PPAR-γ Signaling Pathway.
Oncol Res Treat. 2015; 38(10):511-6.OR

Abstract

BACKGROUND

L-Carnitine has been demonstrated to ameliorate cachectic symptoms. In the present study, we sought to investigate the role of the peroxisome proliferator-activated receptor-γ (PPAR-γ) signaling pathway in the ameliorative effects of L-carnitine on cancer cachexia in a colon-26 tumor-bearing mouse model.

METHODS

The cachectic mice received L-carnitine (p.o.) or etomoxir (i.p.), or pioglitazone hydrochloride (p.o.) or GW9662 (i.p.). The physiological cachexia parameters, biochemical parameters, and serum cytokines were measured. The expression levels of representative molecules in the PPAR-γ signaling pathway were measured by using quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot analysis.

RESULTS

Oral administration of L-carnitine at 9 mg/kg/day improved the cachexia parameters and biochemical parameters in cancer cachectic mice. The elevated serum concentrations of interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) were decreased by L-carnitine. These ameliorative effects of L-carnitine were lessened by the carnitine palmitoyltransferase I (CPT I) inhibitor, etomoxir. The mRNA and protein expression levels of PPAR-α and PPAR-γ were decreased in the livers of cancer cachectic mice and increased after L-carnitine administration, which attenuated the increased mRNA expression levels of sterol-regulatory element-binding protein-1c (SREBP-1c) and fatty acid synthase (FAS). Similar to pioglitazone, L-carnitine augmented the phosphorylation of PPAR-γ and attenuated the expression levels of phospho-p65 and cyclooxygenase (COX)-2. Additionally, the above-mentioned effects of L-carnitine were reversed by GW9662.

CONCLUSION

L-Carnitine exerts its ameliorative effects in cancer cachexia in association with the PPAR-γ signaling pathway.

Authors+Show Affiliations

Department of Gastroenterology, Zhabei District Central Hospital, Shanghai, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26452216

Citation

Jiang, Fang, et al. "L-Carnitine Ameliorates Cancer Cachexia in Mice Partly Via the Carnitine Palmitoyltransferase-Associated PPAR-γ Signaling Pathway." Oncology Research and Treatment, vol. 38, no. 10, 2015, pp. 511-6.
Jiang F, Zhang Z, Zhang Y, et al. L-Carnitine Ameliorates Cancer Cachexia in Mice Partly via the Carnitine Palmitoyltransferase-Associated PPAR-γ Signaling Pathway. Oncol Res Treat. 2015;38(10):511-6.
Jiang, F., Zhang, Z., Zhang, Y., Pan, X., Yu, L., & Liu, S. (2015). L-Carnitine Ameliorates Cancer Cachexia in Mice Partly via the Carnitine Palmitoyltransferase-Associated PPAR-γ Signaling Pathway. Oncology Research and Treatment, 38(10), 511-6. https://doi.org/10.1159/000439550
Jiang F, et al. L-Carnitine Ameliorates Cancer Cachexia in Mice Partly Via the Carnitine Palmitoyltransferase-Associated PPAR-γ Signaling Pathway. Oncol Res Treat. 2015;38(10):511-6. PubMed PMID: 26452216.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - L-Carnitine Ameliorates Cancer Cachexia in Mice Partly via the Carnitine Palmitoyltransferase-Associated PPAR-γ Signaling Pathway. AU - Jiang,Fang, AU - Zhang,Zongqi, AU - Zhang,Yi, AU - Pan,Xiaohui, AU - Yu,Li, AU - Liu,Su, Y1 - 2015/09/11/ PY - 2015/04/21/received PY - 2015/08/17/accepted PY - 2015/10/10/entrez PY - 2015/10/10/pubmed PY - 2016/7/28/medline SP - 511 EP - 6 JF - Oncology research and treatment JO - Oncol Res Treat VL - 38 IS - 10 N2 - BACKGROUND: L-Carnitine has been demonstrated to ameliorate cachectic symptoms. In the present study, we sought to investigate the role of the peroxisome proliferator-activated receptor-γ (PPAR-γ) signaling pathway in the ameliorative effects of L-carnitine on cancer cachexia in a colon-26 tumor-bearing mouse model. METHODS: The cachectic mice received L-carnitine (p.o.) or etomoxir (i.p.), or pioglitazone hydrochloride (p.o.) or GW9662 (i.p.). The physiological cachexia parameters, biochemical parameters, and serum cytokines were measured. The expression levels of representative molecules in the PPAR-γ signaling pathway were measured by using quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot analysis. RESULTS: Oral administration of L-carnitine at 9 mg/kg/day improved the cachexia parameters and biochemical parameters in cancer cachectic mice. The elevated serum concentrations of interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) were decreased by L-carnitine. These ameliorative effects of L-carnitine were lessened by the carnitine palmitoyltransferase I (CPT I) inhibitor, etomoxir. The mRNA and protein expression levels of PPAR-α and PPAR-γ were decreased in the livers of cancer cachectic mice and increased after L-carnitine administration, which attenuated the increased mRNA expression levels of sterol-regulatory element-binding protein-1c (SREBP-1c) and fatty acid synthase (FAS). Similar to pioglitazone, L-carnitine augmented the phosphorylation of PPAR-γ and attenuated the expression levels of phospho-p65 and cyclooxygenase (COX)-2. Additionally, the above-mentioned effects of L-carnitine were reversed by GW9662. CONCLUSION: L-Carnitine exerts its ameliorative effects in cancer cachexia in association with the PPAR-γ signaling pathway. SN - 2296-5262 UR - https://www.unboundmedicine.com/medline/citation/26452216/L_Carnitine_Ameliorates_Cancer_Cachexia_in_Mice_Partly_via_the_Carnitine_Palmitoyltransferase_Associated_PPAR_γ_Signaling_Pathway_ L2 - https://www.karger.com?DOI=10.1159/000439550 DB - PRIME DP - Unbound Medicine ER -