Impact of alcohol cessation on hepatic metabolic signaling during cancer cachexia

The liver is central to macronutrient metabolism, with cancer and alcohol both impacting its function. The objective was to investigate the effects of alcohol use and its cessation, on hepatic gene expression for lipid metabolism and mitochondrial proteins during cachexia inducing distal site cancer.

Male CD2F1 mice were randomized to Control no cancer, Control-Cancer, prior alcohol (PE), PE-cancer, EtOH, or EtOH-cancer groups. Mice consumed control or alcohol (20% kcals from ethanol) liquid diet for 6 weeks, after which PE groups were weaned off alcohol. C26 colon carcinoma cells were implanted and 2 weeks later, livers were collected for RNA, cDNA, RT-PCR and Western blotting.

Cancer lowered body weight and epidydimal adipose tissue weight, led to higher liver weight and greater percent weight loss. Alcohol also increased liver weight and reduced fat mass, while cessation attenuated body weight loss with cancer. Cancer increased genes related to lipid uptake and cholesterol synthesis, while genes for de novo lipogenesis and lipolysis were suppressed in the liver. Distal site cancer led to decrements in hepatic mitochondrial respiratory chain protein content and the mitophagy related proteins, DRP-1 and BNIP3. Alcohol also lowered DRP-1 and BNIP3 content. In non-cancer mice, the cessation of alcohol led to lower expression of cholesterol synthesis genes and higher levels of vATP5A (complex V) of the mitochondrial respiratory chain.

Cessation of alcohol attenuates body weight loss due to cancer but has fewer effects on mitochondrial proteins, and genes regulating lipid balance in the liver.