Avenues of Communication between the Brain and Tissues/Organs Involved in Energy Homeostasis

Abstract

Abstract. 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. Key words:(Endocrine Journal 54: [497][498][499][500][501][502][503][504][505] 2007) THE worldwide prevalence of obesity, which is a major risk factor for numerous disorders, including diabetes, hypertension and heart disease, is increasing at an alarming rate, with major adverse consequences for human health [1]. Body weight is thought to be determined by the balance between energy intake and expenditure. However, alterations in daily food intake and physical activity do not rapidly affect body weight. Why is this? The most plausible explanation is the existence of systems which maintain energy homeostasis throughout the body. Energy homeostasis is maintained by multiple mechanisms that involve gathering information on the body's nutritional status and making appropriate behavioral and metabolic responses to changes in fuel availability. For such inter-organ/ tissue communication, humoral factors, including insulin and adipocytokines, are known to be very important. In addition, we and other research groups have recently reported the autonomic nervous system to play an important role in conveying metabolic information. Using these systems, the brain obtains information on peripheral metabolic status and processes it to send signals which regulate metabolism in the periphery. In particular, the hypothalamus is a primary site of convergence and integration for redundant energy status signaling, which includes central and peripheral neural inputs as well as hormonal and nutritional factors. These pathways of inter-tissue communication are summarized in Fig. 1. Recent advances in this field are reviewed herein.

Ameliorating Effect of Hypothalamic Brain-Derived Neurotrophic Factor Against Impaired Glucose Metabolism After Cerebral Ischemic Stress in Mice

“…Nonomura et al reported that intracerebroventricular injection of BDNF increases hepatic insulin sensitivity and pancreatic insulin content (12). These results suggest that BDNF in the central nervous system is an important regulator of glucose metabolism in peripheral organs via "inter-tissue communication", and the hypothalamus is an essential brain region that directs this system (24). Furthermore, our previous observation showed that hyperglycemia or a decrease in whole-body insulin sensitivity after cerebral ischemia was due to decreased hepatic InsR expression and activity and to the induction of PEPCK and G6Pase (16).…”

Ischemic Stroke and Glucose Intolerance: a Review of the Evidence and Exploration of Novel Therapeutic Targets

“…It was recently reported that the autonomic nervous system plays an important role in conveying metabolic information between the CNS and peripheral organs (68). In particular, the hypothalamus is the primary site of convergence and integration for redundant energy status signaling, which includes central and peripheral neural inputs, as well as hormonal and nutritional factors (Fig.…”

“…Orexins are derived from a single precursor prepro-orexin and act via two types of G-protein-coupled receptors, the orexin-1 (OX1R) and orexin-2 receptors, which have a seventransmembrane topology (70). It was recently reported that the autonomic nervous system plays an important role in conveying metabolic information between the hypothalamus and peripheral organs (68,69). Injection of orexin-A into the ventromedial hypothalamus of mice or rats enhanced insulin-stimulated glucose uptake and glycogenesis in skeletal muscle by activating the sympathetic nervous system (69).…”

Enhancing hepatic mitochondrial fatty acid oxidation stimulates eating in food-deprived mice

“…BECAUSE FOOD is the only source of metabolic fuels, it is reasonable to assume that feedback from metabolism contributes to the control of eating, allowing for the maintenance of a balance between the amount of calories spent and ingested (52,53). The nervous system continuously monitors metabolism to assess the availability of energy-providing fuels such as fatty acids and glucose and to control energy intake and expenditure accordingly.…”