Hedonic and Homeostatic Mechanisms in Hunger Regulation: Insights into Hypothalamic Circuits

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• Bayram Yilmaz, Yeditepe University, Istanbul, Turkey
• Tuesday 15 October 2024, 16:00-17:00
• Hodgkin Huxley Seminar Room, Physiology builiding, Downing Site CB2 3EG.

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Obesity has become a major global public health issue, characterized by a significant imbalance between caloric intake and energy expenditure. While this energy imbalance is the primary driver of obesity, it is essential to recognize that a multitude of genetic, individual, social, and environmental factors also play a critical role in the development of this complex metabolic disorder. Neurons in the hypothalamic arcuate nucleus (ARC), specifically Agouti-Related Peptide (AgRP) and Proopiomelanocortin (POMC) neurons, play crucial roles in regulating hunger and satiety, respectively. Recent findings from our research indicate that chronic high-fat consumption disrupts the regulatory mechanisms of POMC neuron activation by leptin. Furthermore, obesity is associated with significant alterations in neurochemistry and neurotransmission in the brain, particularly within the opioid system. While opioids are generally thought to enhance hedonic appetite through reward pathways, they have also been shown to be widely expressed in neuronal populations that are involved in homeostatic appetite regulation within the hypothalamus. Our studies have demonstrated that consumption of both palatable and non-palatable foods increases hypothalamic opioid release, which directly inhibits AgRP neurons, thus promoting satiety. These findings suggest that hypothalamic opioid signaling may play a critical role in homeostatic appetite regulation and challenge the conventional understanding of orexigenic functions. In this talk, utilization of electrophysiology (including patch-clamp technique), opto/chemogenetic and fluorescent microscopy methods in neuroendocrine research will be reviewed.

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