Energy metabolism in cachexia

Abstract

Cachexia is a wasting disorder that accompanies many chronic diseases including cancer and results from an imbalance of energy requirements and energy uptake. In cancer cachexia, tumor-secreted factors and/or tumor-host interactions cause this imbalance, leading to loss of adipose tissue and skeletal and cardiac muscle, which weakens the body. In this review, we discuss how energy enters the body and is utilized by the different organs, including the gut, liver, adipose tissue, and muscle, and how these organs contribute to the energy wasting observed in cachexia. We also discuss futile cycles both between the organs and within the cells, which are often used to fine-tune energy supply under physiologic conditions. Ultimately, understanding the complex interplay of pathologic energy-wasting circuits in cachexia can bring us closer to identifying effective treatment strategies for this devastating wasting disease.

Keywords: adipose tissue; cachexia; inflammation; liver; skeletal muscle.

Figure 1. Overview of energy consuming processes in cachexia

Tumor‐secreted factors or tumor/host interactions reduce energy uptake and activate energy‐wasting processes in different organ systems, acting on brain/CNS, adipose tissues, gastrointestinal system, liver, and muscles.

Figure 2. Overview of inter‐ and intra‐organ futile energy‐wasting cycles

Futile cycles are mechanisms to regulate and fine‐tune metabolic processes under physiologic conditions. In muscle, adipose and liver, futile cycling is increased in cachectic conditions, and released metabolites are involved in inter‐organ cycles.