Environmental Manipulation and Neuropeptide Effects on Energy Balance and Cancer

Abstract

Social and environmental factors have profound impacts on energy balance and cancer. Yet many experimental studies of the metabolic syndromes and cancer utilize animals in laboratory conditions without adequate social interactions. We recently demonstrate that environments that are more complex and challenging, but not stressful per se, have robust effects on body composition, energy balance, and peripheral cancer progression. One key underlying mechanism is the activation of a specific neuroendocrine brain-adipocyte axis, the hypothalamic-sympatho-neural-adipocyte (HSA) axis. The social, physical, and cognitive stimuli provided by the enriched environments induce brain-derived neurotrophic factor (BDNF) in the hypothalamus and the ensuing sympathetic innervation of adipose tissue. The remodeling of the adipose tissue, including the white-to-brown phenotypic switch and the suppression of leptin, leads to antiobesity and anticancer phenotype. This chapter summarizes this work and discusses how environmental enrichment (EE) can serve as a valuable animal model to study eustress (positive or benign stress), metabolism, cancer, and aging.