Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Program in Neuroscience, Harvard Medical School, Boston, MA, USA. Electronic address:
Published: December 2024
AI Article Synopsis
Article Abstract
When food is freely available, eating occurs without energy deficit. While agouti-related peptide (AgRP) neurons are likely involved, their activation is thought to require negative energy balance. To investigate this, we implemented long-term, continuous in vivo fiber-photometry recordings in mice. We discovered new forms of AgRP neuron regulation, including fast pre-ingestive decreases in activity and unexpectedly rapid activation by fasting. Furthermore, AgRP neuron activity has a circadian rhythm that peaks concurrent with the daily feeding onset. Importantly, this rhythm persists when nutrition is provided via constant-rate gastric infusions. Hence, it is not secondary to a circadian feeding rhythm. The AgRP neuron rhythm is driven by the circadian clock, the suprachiasmatic nucleus (SCN), as SCN ablation abolishes the circadian rhythm in AgRP neuron activity and feeding. The SCN activates AgRP neurons via excitatory afferents from thyrotrophin-releasing hormone-expressing neurons in the dorsomedial hypothalamus (DMH neurons) to drive daily feeding rhythms.
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Program in Neuroscience, Harvard Medical School, Boston, MA, USA. Electronic address:
When food is freely available, eating occurs without energy deficit. While agouti-related peptide (AgRP) neurons are likely involved, their activation is thought to require negative energy balance. To investigate this, we implemented long-term, continuous in vivo fiber-photometry recordings in mice.
Caloric depletion leads to behavioral changes that help an animal find food and restore its homeostatic balance. Hunger increases exploration and risk-taking behavior, allowing an animal to forage for food despite risks; however, the neural circuitry underlying this change is unknown. Here, we characterize how hunger restructures an animal's spontaneous behavior as well as its directed exploration of a novel object.
Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention Ministry of Education, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning, 110122, People's Republic of China.
Background: Epidemiologic researches show that short sleep duration may affect feeding behaviors resulting in higher energy intake and increased risk of obesity, but the further mechanisms that can interpret the causality remain unclear. The circadian rhythm is fine-tuned by the suprachiasmatic nucleus (SCN) as the master clock, which is essential for driving rhythms in food intake and energy metabolism through neuronal projections to the arcuate nucleus (ARC) and paraventricular nucleus (PVN).
Results: We showed that chronic SD-induced aberrant expressions of AgRP/NPY and POMC attributed to compromised JAK/STAT3 signals and reduced energy expenditure in the mice, which can be rescued with AAV-genetic overexpression of BMAL1 into SCN.
Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Key Laboratory of Immune Response and Immunotherapy, CAS Key Laboratory of Brain Function and Disease, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230026, China.
In the face of constantly changing environments, the central nervous system (CNS) rapidly and accurately calculates the body's needs, regulates feeding behavior, and maintains energy homeostasis. The arcuate nucleus of the hypothalamus (ARC) plays a key role in this process, serving as a critical brain region for detecting nutrition-related hormones and regulating appetite and energy homeostasis. Agouti-related protein (AgRP)/neuropeptide Y (NPY) neurons in the ARC are core elements that interact with other brain regions through a complex appetite-regulating network to comprehensively control energy homeostasis.
Objective: The control of energy balance involves neural circuits in the central nervous system, including AGRP neurons in the arcuate nucleus of the hypothalamus (ARC). AGRP neurons are crucial for energy balance and their increased activity during fasting is critical to promote feeding behavior. The activity of these neurons is influenced by multiple signals including those acting on G-protein coupled receptors (GPCR) activating different intracellular signaling pathways.
