Obesity is a rapidly increasing public health concern worldwide as a major risk factor for numerous disorders, including diabetes, hypertension and heart disease. Despite remarkable advances in obesity research over the past 10 years, the molecular mechanisms underlying obesity are still not completely understood. To maintain systemic energy homeostasis, it is important that organs/tissues communicate metabolic information among each other. Obesity-related disorders can be thought of as resulting from dysregulation of this inter-tissue communication. This system has both afferent sensing components and efferent effecter limbs. The afferent signals consist of not only humoral factors, such as nutrients (glucose, fatty acids and amino acids) and adipocytokines (leptin, adiponectin and so on), but also autonomic afferent nerve systems. Both converge on brain centers, most importantly within the hypothalamus, where the signals are integrated, and the direction and magnitude of efferent responses are determined. The efferent elements of this physiological system include those regulating energy inputs and outputs, i.e. food intake and metabolic rates. In this review, we will summarize recent advances in research on metabolic information avenues to the brain, which are important for energy homeostasis.