The Role of CNS Fuel Sensing in Energy and Glucose Regulation
Section snippets
CNS Energy Balance Regulation: Integrating Lipostatic and Glucostatic Theories
Since the end of the 19th century, several efforts have been made to determine the CNS’ role in the regulation of energy metabolism. In the 1950s, Gordon Kennedy proposed that energy homeostasis is maintained through regulation of body fat, as a result of feedback signals arising from the fat depots that are sensed by the brain.13 The hormones leptin and insulin, respectively synthesized in adipose tissue and pancreas, circulate in proportion to body fat.14 Hence, they inform the CNS that
CNS Fuel-Sensing Mechanisms: AMPK and mTOR
Studies have demonstrated over the last 50 years that the glucostatic and lipostatic theories both have important limitations and caveats.32, 64, 65 The result has been a need for new conceptualizations concerning the neuronal mechanisms that regulate food intake and energy homeostasis. In the following section, we would like to propose that signals derived from both stored and immediately available fuels converge in the same intracellular signaling cascades in the CNS, where they are monitored
mTOR
In 1991, the target for the immunosuppressant macrolide rapamycin was identified and termed Target Of Rapamycin or TOR. The mammalian isoform (called mTOR and also known as FRAP, RAFT, RAPT, or SEP) is a ∼ 280-KDa protein, member of the phosphatidylinositol kinase–related protein kinase family.87 mTOR is a highly conserved serine-threonine kinase, and its activity controls critical aspects of cell growth regulation, including transcription, translation initiation and elongation, and cell-cycle
The Role of CNS Fuel-Sensing Pathways in Causing and Treating Obesity
Understanding the basic mechanisms by which caloric intake is matched to caloric expenditure does not necessarily result in new therapies for obesity. While the prevailing data make an excellent case that CNS fuel-sensing pathways are an important part of how energy balance is regulated, several issues make them difficult to target for the treatment of obesity. First, these fuel-sensing pathways are critical components of regulating cellular function. As a result, their role in peripheral cells
Conclusions
The brain is a critical organ for coordinating complex metabolic processes across various tissues that ensure the right nutrients reach the tissues at the time they need them. To do so, metabolic pathways in the CNS must be able to supervise fuel availability in both a direct and an indirect manner. Part of the direct monitoring of fuels involves neurons using highly conserved intracellular fuel-sensing pathways able to provide readout of cellular fuel availability to guide the organism in
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History of nutrition and inflammation
2022, Diet, Inflammation, and HealthFunctional heterogeneity of POMC neurons relies on mTORC1 signaling
2021, Cell ReportsCitation Excerpt :Within the arcuate nucleus (ARC) of the hypothalamus, two neuronal populations respectively expressing pro-opiomelanocortin (POMC) and Agouti-related peptide (AgRP) oppositely control food intake as a result of antagonistic effects on the central melanocortin receptors type 4 (MC4R) (Krashes et al., 2016). POMC and AgRP neurons respond to nutrient and hormonal signals reflecting changes in energy availability (Cota et al., 2007; Krashes et al., 2016). Energy deficit activates AgRP neurons, which drive food seeking and intake through the release of the MC4R antagonist AgRP, the neuropeptide Y (NPY), and the inhibitory neurotransmitter γ-aminobutyric acid (GABA) (Tong et al., 2008).
Hypothalamic hormone-sensitive lipase regulates appetite and energy homeostasis
2021, Molecular MetabolismHypothalamic peptide and nutrient sensors gene expression in the hypothalamus of neonatal rat
2020, Brain Research BulletinCitation Excerpt :As for the products derived from protein digestion (peptones), the answers appear between 13 and 18 postnatal days (Weller and Tsitolovskya, 2004). The nutrient sensors are able to influence the activity of each other, fasting and the low level of cellular energy leads to activation of AMPK which is capable of inhibiting mTOR (Cota et al., 2007). Fasting and non-caloric load induced gastric increase in gene expression of orexigenic neuropeptides, NPY and AgRP, on the eighteenth day of life.