G. Wu

Resting energy expenditure and body composition in patients with newly detected cancer

BACKGROUND & AIMSnElevated resting energy expenditure (REE) may be a major determinant in the development of cancer cachexia. The aim of the study was to evaluate REE and body composition in cancer patients and find out the relationship between energy expenditure and substrate utilization.nnnMETHODSnMeasured resting energy expenditure (mREE), carbohydrate oxidation (C-O), and fat oxidation (F-O) were measured by indirect calorimetry in 714 cancer patients and 642 controls. Extracellular fluid (ECF), intracellular fluid (ICF), and total water (TW) were measured by bioelectrical impedance appliance; fat mass (FM), fat free mass (FFM), and body cell mass (BCM) were further determined.nnnRESULTSnCompared with the controls, cancer patients showed no significant difference in mREE, but had higher mREE/FFM and mREE/pREE. 46.7% (n=333) of cancer patients were hypermetabolic, 43.5% (n=310) normometabolic, and 9.8% (n=71) hypometabolic; whereas 25.2% (n=162) of control subjects were hypermetabolic, 56.5% (n=363) normometabolic, and 18.3% (n=117) hypometabolic. Cancer patients showed an increase in F-O, ECF, TW/BW and ECF/BW; and a decrease in C-O, npRQ, ICF, ICF/BW. REE was correlated to substrate oxidation rate. Cancer patients exhibited an elevation in FM, FM/BW, FFM, and BCM, and a decrease in FFM/BW.nnnCONCLUSIONSn1. Cancer patients had elevated REE. Cancer type, pathological stage and duration of disease influenced REE. 2. Aberrations in substrate utilization may contribute to the elevated REE in cancer patients. 3. FM, FFM, and BCM diminished in cancer patients, which may be related to the elevated REE.

Role of β1‐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 β1‐adrenoceptor (ADRB1), β2‐adrenoceptor (ADRB2), β3‐adrenoceptor (ADRB3), α2C‐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. β1‐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. β1‐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. (Cancer Sci 2010)

Interleukin-6 stimulates aerobic glycolysis by regulating PFKFB3 at early stage of colorectal cancer

Chronic inflammation is a well-known etiological factor for colorectal cancer (CRC) and cancer cells are known to preferentially metabolize glucose through aerobic glycolysis. However, the connection between chronic inflammation and aerobic glycolysis in the development of CRC is largely unexplored. The present study investigated whether interleukin-6 (IL-6), a pro-inflammatory cytokine, promotes the development of CRC by regulating the aerobic glycolysis and the underlying molecular mechanisms. In colitis-associated CRC mouse, anti-IL-6 receptor antibody treatment reduced the incidence of CRC and decreased the expression of key genes in aerobic glycolysis, whereas the plasma concentrations of glucose and lactate were not affected. Consistently, IL-6 treatment stimulated aerobic glycolysis, upregulated key genes in aerobic glycolysis and promoted cell proliferation and migration in SW480 and SW1116 CRC cells. 6-phoshofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3) was the most downregulated gene by anti-IL-6 receptor antibody in colorectal adenoma tissues. Further analysis in human samples revealed overexpression of PFKFB3 in colorectal adenoma and adenocarcinoma tissues, which was also associated with lymph node metastasis, intravascular cancer embolus and TNM stage. In addition, the effect of IL-6 on CRC cells can be abolished by knocking down PRKFB3 through siRNA transfection. Our data suggest that chronic inflammation promotes the development of CRC by stimulating aerobic glycolysis and IL-6 is functioning, at least partly, through regulating PFKFB3 at early stage of CRC.

Prevention of Muscle Wasting by CRISPR/Cas9-mediated Disruption of Myostatin In Vivo

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