Proteostasis in thermogenesis and obesity

The proper production, degradation, folding and activity of proteins, proteostasis, is essential for any cellular function. From single cell organisms to humans, selective pressures have led to the evolution of adaptive programs that ensure proteins are properly produced and disposed of when necessary. Environmental factors such as temperature, nutrient availability, pathogens as well as predators have greatly influenced the development of mechanisms such as the unfolded protein response, endoplasmic reticulum-associated protein degradation and autophagy, working together in concert to secure cellular proteostasis. In our modern society, the metabolic systems of the human body face the distinct challenge of changed diets, chronic overnutrition and sedentary lifestyles. Obesity and excess white adipose tissue accumulation are linked to a cluster of metabolic diseases and disturbed proteostasis is a common feature. Conversely, processes that promote energy expenditure such as exercise, shivering as well as non-shivering thermogenesis by brown adipose tissue (BAT) and beige adipocytes counteract metabolic dysfunction. Here we review the basic concepts of proteostasis in obesity-linked metabolic diseases and focus on adipocytes, which are critical regulators of mammalian energy metabolism.