Cell Sub-Journal: Reveals the neural loop that boosts appetite after eating fat meat.

Learn about the latest progress in neuroscience ● click the blue word to pay attention to us ● high fat diet induces metabolic disorders, leading to diabetes, obesity and other metabolic diseases.in addition, after high-fat diet, the body and cerebral cortex of Hippo were deficient in glucose, which resulted in inattention and delayed reaction.high fat diet can promote acute hypersensitivity, and long-term high-fat diet will change the secretion of gastrointestinal hormones and damage the sensitivity of vagal afferent.the arcuate nucleus (ARC) of hypothalamus is the most frequently studied area of diet control. There are two types of neurons related to diet in this brain area: promoting AgRP neurons and inhibiting POMC neurons.after high-fat diet, weight gain will generally occur, resulting in obesity.Professor Jens C. bruning of the Max Planck Institute for metabolism in Germany discovered in 2019 that after the deletion of ceramide synthetase 6, even if the high-fat diet is continued, there is no fat accumulation in the liver and weight loss.recently, Professor Jens C. bruning found that after shutting down a new type of neuron, he would not worry about eating fat.on April 15, 2020, Professor Jens C. bruning made a new discovery in the field of energy metabolism. His research results were published in the journal Neuron, revealing a new type of neuron that promotes appetite in the face of food temptation - PNOC neurons, and explains part of the reason why appetite increases after eating fat and other foods in daily life.using transcriptomics, the researchers found that the hypothalamic neurons of mice fed with high-fat diet highly expressed neuropeptide PNOC gene, and further analyzed the activated cell clusters to determine that PNOC is a characteristic marker of activated neurons, that is, neurons expressing neuropeptide PNOC can be activated after high-fat diet.what is PNOC? It is the precursor of pain sensitive peptide (also known as orphanin) is a kind of opioid peptide. Intracerebroventricular injection of pain sensitive peptide can make mice hyperalgesia and reduce movement.using ribosomal affinity purification technology, we found that PNOC neurons are a kind of cell group different from AgRP neurons and POMC neurons, and their mRNA is enriched in the expression of molecular characteristics of inhibitory neurons.in situ hybridization showed that about 80% of the PNOC neurons were co labeled with the inhibitory neuron marker VGAT. Subsequent electrophysiological experiments further demonstrated that PNOC neurons were inhibitory neurons.in order to further study the role of PNOC neurons in the regulation of food intake, PNOC knockout mice perform normally under normal diet, but lose weight significantly after a week of high-fat diet, that is to say, after PNOC knockout mice do not like the high-fat food that once fascinated them.surprisingly, PNOC knockout mice preferred to drink water at the early stage of high-fat diet, and their feeding behavior decreased.the researchers injected AAV virus into the arc brain region of AgRP CRE, POMC CRE and PNOC CRE mice, and found that PNOC neurons Co located with POMC neurons, but did not exist with AgRP.this indicates that there is co labeling between PNOC neurons and POMC neurons in arc.the inhibitory postsynaptic currents appeared in PMOC neurons after PNOC neurons were activated by electrogenerated light in vitro.this current can be blocked by GABA-A receptor antagonist.this indicates that there is an inhibitory microcircuit between PNOC neurons and POMC neurons, which has not been found before.PNOC neurons also have different neural projections. Specifically, arc AgRP neurons and arc POMC neurons densely project to the paraventricular nucleus (PVN), but arc-pnoc neurons do not project to this brain area.arc-pnoc neurons mainly projected to BNST, and a small number of arc-pnoc neurons projected to the nucleus rigidus and dorsal raphe nucleus.the researchers hybridized PNOC CRE mice with CRE dependent excitatory opsin ChR2 expression mice. After blue light activation, the high-fat diet behavior of mice was promoted, and the promotion effect disappeared after stopping light activation.light activated PNOC projected by arc into the lateral nucleus did not promote the feeding behavior of mice, but stimulated the PNOC projected by arc to BNST.researchers injected AAV apoptotic virus into the arc brain region of PNOC CRE mice, which can specifically cause the death of PNOC neurons in the arc brain region, so that the mice will not gain weight even after the high-fat diet is given, that is, when the type of neurons are turned off, they will not gain weight.in general, we found that PNOC neurons promote excessive diet after acute high-fat diet, which provides a new goal for the prevention and treatment of obesity and related metabolic diseases.References: PNOC nerves promote hyperphagia and obsity upon high fat diet feeding!