Skeletal muscle metabolism in physiology and in cancer disease

Giordano, A; Calvani, Menotti; Petillo, Orsolina; Cartenı̀, Maria; Melone, Mariarosa Anna Beatrice; Peluso, Gianfranco

doi:10.1002/jcb.10601

Cited by 60 publications

(52 citation statements)

References 110 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…CPT-1 catalyzes the rate-limiting step in this passage and is site for intracellular regulation of fatty acid metabolism, with malonyl-CoA acting as a physiological inhibitor. 34,35 Other studies found a physical association between CPT-1 and Bcl-2 on the outer mitochondrial membrane providing an additional potential link between CPT-1 and the regulation of apoptosis. 15 Intrigued by these observations, we have explored the rate of b-oxidation as well as the intermediates of b-oxidation and CPT-1 activity in hepatocytes treated with the activated BH3-only protein, tBid.…”

Section: Fatty Acid Oxidation Alteration Induced By Tbid a Giordano Ementioning

confidence: 97%

tBid induces alterations of mitochondrial fatty acid oxidation flux by malonyl-CoA-independent inhibition of carnitine palmitoyltransferase-1

et al. 2005

View full text Add to dashboard Cite

Recent studies suggest a close relationship between cell metabolism and apoptosis. We have evaluated changes in lipid metabolism on permeabilized hepatocytes treated with truncated Bid (tBid) in the presence of caspase inhibitors and exogenous cytochrome c. The measurement of b-oxidation flux by labeled palmitate demonstrates that tBid inhibits b-oxidation, thereby resulting in the accumulation of palmitoyl-coenzyme A (CoA) and depletion of acetyl-carnitine and acylcarnitines, which is pathognomonic for inhibition of carnitine palmitoyltransferase-1 (CPT-1). We also show that tBid decreases CPT-1 activity by a mechanism independent of both malonyl-CoA, the key inhibitory molecule of CPT-1, and Bak and/or Bax, but dependent on cardiolipin decrease. Overexpression of Bcl-2, which is able to interact with CPT-1, counteracts the effects exerted by tBid on b-oxidation. The unexpected role of tBid in the regulation of lipid b-oxidation suggests a model in which tBid-induced metabolic decline leads to the accumulation of toxic lipid metabolites such as palmitoyl-CoA, which might become participants in the apoptotic pathway.

show abstract

Section: Fatty Acid Oxidation Alteration Induced By Tbid a Giordano Ementioning

confidence: 97%

tBid induces alterations of mitochondrial fatty acid oxidation flux by malonyl-CoA-independent inhibition of carnitine palmitoyltransferase-1

et al. 2005

View full text Add to dashboard Cite

show abstract

“…Increased levels of uncoupling proteins, accompanied by reduced levels of ATP, have been reported in the skeletal muscle of patients with cancer [105,106]. Furthermore, it has been proposed that patients with cancer, particularly those with anorexiacachexia, have altered muscle protein metabolism [107].…”

Section: Muscle Metabolism/atp Dysregulationmentioning

confidence: 99%

Mechanisms of Cancer-Related Fatigue

Ryan¹,

Carroll²,

Ryan³

et al. 2007

The Oncologist

493

408

View full text Add to dashboard Cite

Cancer-related fatigue (CRF) is one of the most prevalent symptoms patients with cancer experience, both during and after treatment. CRF is pervasive and affects patients' quality of life considerably. It is important, therefore, to understand the underlying pathophysiology of CRF in order to develop useful strategies for prevention and treatment. At present, the etiology of CRF is poorly understood and the relative contributions of the neoplastic disease, various forms of cancer therapy, and comorbid conditions (e.g., anemia, cachexia, sleep disorders, depression) remain unclear. In any individual, the etiology of CRF probably involves the dysregulation of several physiological and biochemical systems. Mechanisms proposed as underlying CRF include 5-HT neurotransmitter dysregulation, vagal afferent activation, alterations in muscle and ATP metabolism, hypothalamic-pituitary-adrenal axis dysfunction, circadian rhythm disruption, and cytokine dysregulation. Currently, these hypotheses are largely based on evidence from other conditions in which fatigue is a characteristic, in particular chronic fatigue syndrome and exercise-induced fatigue. The mechanisms that lead to fatigue in these conditions provide a theoretical basis for future research into the complex etiology of this distressing and debilitating symptom. An understanding of relevant mechanisms may offer potential routes for its prevention and treatment in patients with cancer.

show abstract

“…Disturbances in liver and muscle metabolism are at the center of numerous diseases [1,2]. Metabolome and lipidome analyses can be valuable and complementary tools to study the metabolism of healthy or diseased tissue [3,4].…”

Section: Introductionmentioning

confidence: 99%