Role of beta1-adrenoceptor in increased lipolysis in cancer cachexia.
Increased production of hormone-sensitive lipase (HSL) protein has been demonstrated to be the major cause behind enhanced lipolysis in cancer cachexia. The mechanism governing this alteration is unknown and was presently investigated. This study was conducted to detect the expression of relevant receptors in the adipocytes of cancer cachexia patients, and to elucidate their implication in the increased lipolysis. Gene expressions of beta1-adrenoceptor (ADRB1), beta2-adrenoceptor (ADRB2), beta3-adrenoceptor (ADRB3), alpha2C-adrenoceptor (ADRA2C), natriuretic peptide receptor A (NPRA), insulin receptor (INSR), and HSL were determined in adipose tissues of 34 patients by real-time PCR. Protein levels of ADRB1 and HSL were determined by western blot analysis. beta1-Adrenoceptor (ADRB1) was also detected by immunofluorescence staining. mRNA expressions of both ADRB1 and HSL were approximately 50% elevated selectively in the cachexia group, whereas mRNA levels of the other receptors were unchanged. beta1-Adrenoceptor (ADRB1) protein expression was 1.5-fold increased in cachexia as compared with the cancer controls, and 3-fold increased as compared with nonmalignant controls, and was confirmed as a membrane protein in adipocytes by immunofluorescence. Hormone-sensitive lipase (HSL) protein expression was 2-2.5-fold increased selectively in cachectic patients. There was a positive correlation between the protein expressions of ADRB1 and HSL. As much as approximately 50% of the variations in HSL protein expression could be explained by variations in ADRB1 protein expression. There was a link between ADRB1 protein level and lipolytic rate. Increased ADRB1 expression may account for some of the functional changes of HSL in patients with cancer cachexia.
Cao
Dong-xing
DX
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Wu
Guo-hao
GH
Yang
Zi-ang
ZA
Zhang
Bo
B
Jiang
Yi
Y
Han
Yu-song
YS
He
Guo-dong
GD
Zhuang
Qiu-lin
QL
Wang
Yan-fu
YF
Huang
Zhong-lin
ZL
Xi
Qiu-lei
QL
D000273:Adipose Tissue / Q000033:anatomy & histology / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D002100:Cachexia / Q000503:physiopathology*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D054770:G-Protein-Coupled Receptor Kinase 3 / Q000235:genetics; D005770:Gastrointestinal Neoplasms / Q000235:genetics / Q000601:surgery; D006801:Humans; D008066:Lipolysis / Q000235:genetics* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D018579:Patient Selection; D016133:Polymerase Chain Reaction; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D011972:Receptor, Insulin / Q000235:genetics; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics / Q000502:physiology*; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics
C547787:ADRB1 protein, human; D005230:Fatty Acids, Nonesterified; D012334:RNA, Neoplasm; D018342:Receptors, Adrenergic, beta-1; D011972:Receptor, Insulin; D054770:G-Protein-Coupled Receptor Kinase 3; C517848:GRK3 protein, human; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A