1. ¹Obesity Biology Unit, Division of Metabolic & Cellular Medicine, School of Clinical Sciences, University of Liverpool, Liverpool L69 3GA, UK
2. ²Pharmaceutical Sciences Research Institute, Aston University, Birmingham, B4 7ET, UK
3. ³Department of Veterinary Pathology, University of Liverpool, Liverpool L69 3BX, UK
4. ⁴The Henry Wellcome Laboratory of Molecular and Cellular Gastroenterology, School of Clinical Sciences, University of Liverpool, Liverpool L69 3BX, UK

Correspondence: Dr C Bing, E-mail: bing@liverpool.ac.uk

Revised 16 August 2006; Accepted 22 August 2006; Published online 3 October 2006.

Abstract

Extensive loss of adipose tissue is a hallmark of cancer cachexia but the cellular and molecular basis remains unclear. This study has examined morphologic and molecular characteristics of white adipose tissue in mice bearing a cachexia-inducing tumour, MAC16. Adipose tissue from tumour-bearing mice contained shrunken adipocytes that were heterogeneous in size. Increased fibrosis was evident by strong collagen-fibril staining in the tissue matrix. Ultrastructure of 'slimmed' adipocytes revealed severe delipidation and modifications in cell membrane conformation. There were major reductions in mRNA levels of adipogenic transcription factors including CCAAT/enhancer binding protein alpha (C/EBP), CCAAT/enhancer binding protein beta, peroxisome proliferator-activated receptor gamma, and sterol regulatory element binding protein-1c (SREBP-1c) in adipose tissue, which was accompanied by reduced protein content of C/EBP and SREBP-1. mRNA levels of SREBP-1c targets, fatty acid synthase, acetyl CoA carboxylase, stearoyl CoA desaturase 1 and glycerol-3-phosphate acyl transferase, also fell as did glucose transporter-4 and leptin. In contrast, mRNA levels of peroxisome proliferators-activated receptor gamma coactivator-1alpha and uncoupling protein-2 were increased in white fat of tumour-bearing mice. These results suggest that the tumour-induced impairment in the formation and lipid storing capacity of adipose tissue occurs in mice with cancer cachexia.