Energy homeostasis depends on the regulation of hypothalamic neurons by leptin, an adipocyte hormone whose circulating levels communicate body energy stores. Leptin activates the transcription factor signal transducer and activator of transcription 3 (Stat3) in hypothalamic neurons, including neuronal subtypes producing Agouti-related protein (Agrp), a neuropeptide that stimulates feeding. Prev...

The neural mechanisms underlying hunger are poorly understood. AgRP neurons are activated by energy deficit and promote voracious food consumption, suggesting these cells may supply the fundamental hunger drive that motivates feeding. However recent in vivo recording experiments revealed that AgRP neurons are inhibited within seconds by the sensory detection of food, raising the question of how...

Obesity-related diseases such as diabetes and dyslipidemia result from metabolic alterations including the defective conversion, storage and utilization of nutrients, but the central mechanisms that regulate this process of nutrient partitioning remain elusive. As positive regulators of feeding behaviour, agouti-related protein (AgRP) producing neurons are indispensible for the hypothalamic int...

Mitochondria are key organelles in the maintenance of cellular energy metabolism and integrity. Here, we show that mitochondria number decrease but their size increase in orexigenic agouti-related protein (Agrp) neurons during the transition from fasted to fed to overfed state. These fusion-like dynamic changes were cell-type specific, as they occurred in the opposite direction in anorexigenic ...

Neuropeptide Y (NPY) and agouti-related peptide (AgRP) stimulate feeding, whereas NPY also facilitates the estrogen-mediated preovulatory GnRH surge. In addition to regulating reproductive function, estrogen also acts as an anorexigenic hormone, although it is not yet known which hypothalamic neurons are involved in this process. We hypothesize that estrogen may directly control hypothalamic NP...

Energy homeostasis depends on the regulation of hypothalamic neurons by leptin, an adipocyte hormone whose circulating levels communicate body energy stores. Leptin activates the transcription factor Signal Transducer and Activator of Transcription 3 (Stat3) in hypothalamic neurons, including neuronal subtypes producing Agouti-related protein (Agrp), a neuropeptide which stimulates feeding. Pre...

Like obesity, prolonged food deprivation induces severe hepatic steatosis; however, the functional significance of this phenomenon is not well understood. In this study, we show that the fall in plasma leptin concentration during fasting is required for the development of hepatic steatosis in mice. Removal of leptin receptors from AGRP neurons diminishes fasting-induced hepatic steatosis. Furth...

Agouti-related protein (AGRP) is a homolog of the agouti protein and acts as an antagonist of peptides derived from propiomelanocortin through melanocortin receptors. This peptide is produced mainly in the hypothalamus, particularly during negative energy balance and influences increased food intake. In the hypothalamus, this peptide is co-expressed in arcuate nuclei with neuropeptide Y, anothe...

The current obesity epidemic and lack of efficient therapeutics demand a clear understanding of the mechanism underlying body weight regulation. Despite intensive research focus on obesity pathogenesis, an effective therapeutic strategy to treat and cure obesity is still lacking. Exciting studies in last decades have established the importance of hypothalamic agouti-related protein-expressing n...

The nervous system evolved to coordinate flexible goal-directed behaviors by integrating interoceptive and sensory information. Hypothalamic Agrp neurons are known to be crucial for feeding behavior. Here, however, we show that these neurons also orchestrate other complex behaviors in adult mice. Activation of Agrp neurons in the absence of food triggers foraging and repetitive behaviors, which...