Catabolism of adipose tissue by a tumour‐produced lipid‐mobilising factor

Khan, Syrah; Tisdale, Michael J.

doi:10.1002/(sici)1097-0215(19990129)80:3<444::aid-ijc18>3.3.co;2-l

Cited by 16 publications

(22 citation statements)

References 12 publications

(15 reference statements)

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“…Previous studies (Khan and Tisdale, 1999) have shown propranolol to act as a non-compedative inhibitor of the induction of lipolysis in murine white adipocytes by LMF. This suggests that it may act at a site distal to the b3-AR and may attenuate the action of two b3 agonists to different extents.…”

Section: Discussionmentioning

confidence: 92%

“…Plasma membranes were isolated from epididymal adipocytes, as previously described (Khan and Tisdale, 1999). Briefly isolated adipocytes were homogenized in 250 mM sucrose, 2 mM EGTA and 10 mM Tris HCl pH 7.4, followed by centrifugation at 30 000 g for 1 h at 48C.…”

Section: Adenylate Cyclase Assaymentioning

confidence: 99%

“…Pharmacological studies indicate that the b-receptor responsible for the stimulation of oxygen consumption in BAT is exclusively of the b3-subtype (Howe, 1993). Induction of lipolysis in epididymal adipocytes by LMF was attenuated by the b-adrenergic receptor blocker propranolol (Khan and Tisdale, 1999), while the biphasic effect of GTP on cyclic AMP production by LMF in adipocyte plasma membranes suggests a receptor associated with both Gs and Gi. Only b3 and not b1-AR interact with Gi in adipocyte membranes (Granneman, 1995).…”

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confidence: 91%

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Role of β3-adrenergic receptors in the action of a tumour lipid mobilizing factor

2002

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Induction of lipolysis in murine white adipocytes, and stimulation of adenylate cyclase in adipocyte plasma membranes, by a tumour-produced lipid mobilizing factor, was attenuated by low concentrations (10 77 -10 75 M) of the specific b3-adrenoceptor antagonist SR59230A. Lipid mobilizing factor (250 nM) produced comparable increases in intracellular cyclic AMP in CHOK1 cells transfected with the human b3-adrenoceptor to that obtained with isoprenaline (1 nM). In both cases cyclic AMP production was attenuated by SR59230A confirming that the effect is mediated through a b3-adrenoceptor. A non-linear regression analysis of binding of lipid mobilizing factor to the b3-adrenoceptor showed a high affinity binding site with a Kd value 78+45 nM and a B max value (282+1 fmole mg protein 71 ) comparable with that of other b3-adrenoceptor agonists. These results suggest that lipid mobilizing factor induces lipolysis through binding to a b3-adrenoceptor.

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Section: Discussionmentioning

confidence: 92%

Section: Adenylate Cyclase Assaymentioning

confidence: 99%

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confidence: 91%

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Role of β3-adrenergic receptors in the action of a tumour lipid mobilizing factor

2002

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“…This lipolysis is activated by the stimulation of adenylate cyclase in a GTP-dependent fashion and is proposed to be mediated by β3 adrenergic receptors [66][67][68]. When mice are treated with LMF/ZAG, elevated serum levels of glycerol and 3-hydroxybutyrate are observed as well as an increase of oxygen usage by BAT is observed, demonstrating the role of LMF/ZAG in stimulating lipid utilization [66].…”

Section: Lipid Mobilizing Factormentioning

confidence: 99%

Pancreatic Cancer Cachexia: Current Concepts and Clinical Management

Guan¹,

Shinde²,

Hendifar³

2017

Frailty and Sarcopenia - Onset, Development and Clinical Challenges

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There has been great progress over the last decade in understanding the pathophysiology of cachexia associated with pancreatic cancer. However, there is a large need to ind better therapeutic options to successfully manage this complex and challenging condition. Patients with pancreatic cancer have some of the highest prevalence and often the most severe degrees of cachexia, which is described as a multifactorial metabolic syndrome that is associated with unintended weight loss of adipose tissue and skeletal muscle in the seting of anorexia. This chapter will review the current concepts surrounding pancreatic cancer cachexia, its clinical diagnosis, pathophysiology, and its known and proposed therapeutics. A multimodal approach utilizing nutritional support and pharmaceutical therapies is proposed to lead to the most successful management of pancreatic cancer cachexia.Keywords: pancreatic cancer, cachexia, anorexia, metabolic syndrome, catabolism IntroductionIn western countries, pancreatic cancer represents the fourth leading cause of cancer-related death [1]. Among the many complications associated with this disease, cachexia marked by progressive weight loss represents one of the most distressing features related to pancreatic cancer. Cachexia is a multidimensional wasting syndrome that is characterized by unintended loss of both adipose tissue and lean body mass (LBM) that cannot be fully reversed through conventional nutritional support. It is a complex metabolic disorder frequently described in pancreatic cancer and represents a signiicant physical and psychological burden in approximately 80% of pancreatic cancer patients during the disease progression [2]. The complications © 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. associated with cachexia, which include immobility, impaired immunity, and severe respiratory muscle impairment leading to cardiopulmonary failure, result in death in up to one-third of pancreatic cancer patients [3]. Cachectic patients are observed to have lower physical function, decreased tolerance to chemotherapy and radiation treatment, and generally worse prognosis than those with stable weight. Poorer outcomes after pancreaticoduodenectomy have also been observed in patients with preoperative signs of cachexia [4].While research over the past decade has provided new insights regarding the pathogenesis of pancreatic cancer cachexia, the mechanistic pathology of this condition is still not entirely understood. In this chapter, we will provide a review of the current concepts, potential therapeutic targets, and management of this signiicant clinical condition. Classiication and progression of cancer cachexiaCachexia has been established to be a common adverse efect of cancer. An international consensus in 2011 deined cachexia as a ...

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“…DEAE cellulose (10 g l -1 of original urine) was added and the mixture was stirred for 2 h at 4˚C. The DEAE-cellulose was recovered by low speed centrifugation and LMF bioactivity, determined by glycerol release from epididymal adipocytes (Khan and Tisdale, 1999), was eluted with 0.5 M NaCl in 10 mM Tris. HCl, pH 8.0.…”

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confidence: 99%

Effect of a tumour-produced lipid-mobilizing factor on protein synthesis and degradation

Islam-Ali

Tisdale

2001

Br J Cancer

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Treatment of murine myoblasts, myotubes and tumour cells with a tumour-produced lipid mobilizing factor (LMF), caused a concentration-dependent stimulation of protein synthesis, within a 24 h period. There was no effect on cell number or [ 3 H] thymidine incorporation, but a similar concentration-dependent stimulation of 2-deoxyglucose uptake. LMF produced an increase in intracellular cyclic AMP levels, which was linearly (r 2 = 0.973) related to the increase in protein synthesis. The effect of LMF was attenuated by the adenylate cyclase inhibitor MDL 12330A , and was additive with the stimulation produced by forskolin. Both propranolol (10 μM) and the specific β 3 -adrenergic receptor antagonist SR 59230A (10 –5 M), significantly reduced the stimulation of protein synthesis induced by LMF. Protein synthesis was also increased by 69% ( P = 0.006) in soleus muscles of mice administered LMF, while there was a 26% decrease in protein degradation ( P = 0.03). While LMF had no effect on the lysosomal enzymes, cathepsins B and L, there was a decrease in proteasome activity, as determined both by the ‘chymotrypsin-like’ enzyme activity, as well as expression of proteasome α-type subunits, determined by Western blotting. These results show that in addition to its lipid-mobilizing activity LMF also increases protein accumulation in skeletal muscle both by an increase in protein synthesis and a decrease in protein catabolism. © 2001 Cancer Research Campaign http://www.bjcancer.com

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Catabolism of adipose tissue by a tumour‐produced lipid‐mobilising factor

Cited by 16 publications

References 12 publications

Role of β3-adrenergic receptors in the action of a tumour lipid mobilizing factor

Role of β3-adrenergic receptors in the action of a tumour lipid mobilizing factor

Pancreatic Cancer Cachexia: Current Concepts and Clinical Management

Effect of a tumour-produced lipid-mobilizing factor on protein synthesis and degradation

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