How Energy Shifts Lead to Systemic Illness

Why do chronic inflammatory diseases (CIDs) such as rheumatoid arthritis (RA) or systemic lupus erythematosus affect the whole body and produce myriad debilitating and disabling symptoms that make people sick? Is this clinical pattern of systemic involvement an unfortunate byproduct of sustained inflammation or, in an unexpected way, is it an adaptive program positively selected during evolution?

The systemic disease sequelae in CIDs are many and represent some of the major problems for which patients seek medical attention and require treatment. These sequelae include the following:

• Depressive symptoms;
• Fatigue;
• Anorexia;
• Malnutrition;
• Muscle wasting (cachexia);
• Cachectic obesity;
• Insulin resistance with hyperinsulinemia;
• Dyslipidemia;
• Increase of adipose tissue in the proximity of inflammatory lesions;
• Alterations of steroid hormone axes (think of androgen loss and others);
• Elevated sympathetic tone;
• Decreased parasympathetic tone;
• Inflammation-related anemia; and
• Osteopenia.

This article reviews recent research on the impact of inflammation on energy homeostasis in the organism and advances the hypothesis that the systemic sequelae of CID result from prolonged energy requirements of an activated immune system and are inherent in disease pathogenesis. To integrate emerging data from studies in metabolism, neuroendocrinology, and immunology, I propose a new model to explain sometimes baffling symptomatology and to find a common denominator of systemic disease sequelae in CIDs.

Energy Distribution and Regulation

In the human body, the distribution of energy-rich fuels is key to survival and is tightly regulated, involving several organs. Uptake of external energy occurs in the intestinal tract (external energy-rich fuels: glucose, amino acids, fatty acids; maximum uptake per day of 20,000 kJ). Storage happens in fat tissue (12 kg of triglycerides in the body=500,000 kJ), the liver (150 g glycogen=2,500 kJ), and muscles (300 g glycogen=5,000 kJ; 6–7 kg protein=50,000 kJ). We use approximately 10,000 kJ/ day in our sedentary way of life. More data for comparison are provided in Table 1( p. 26).^2-8

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Figure 1: Neuroendocrine mechanisms of energy storage and energy provision. Energy-rich fuels are taken up into the body and are stored in liver, fat tissue, and muscle. Bone stores calcium and phosphorus. The respective hormones are indicated in green. Energetic fuels are released from stores by hormonal axes in red text below the storage bowl. In the case of an activated immune system, energy-rich fuels are redirected to the immune system. ASD=androstenedione; Ca=calcium; DHEA=dehydroepiandrosterone; IGF-1=insulin-like growth factor; P=phosphorus; PTH=parathyroid hormone; Vit. D=vitamin D.

Storage of energy is maximal when resources from the food supply are available ad libitum and energy consumers such as brain, muscles, and others are minimally active. Note that the central nervous system, muscles, and the immune system are the major energy consumers in the body, with each utilizing approximately 2,000–2,500 kJ/day.