Endocrine Abstracts

Neurons expressing the agouti-related protein (AgRP) and the pro-opiomelanocortin (POMC) are part of the central system responsible for regulating energy balance and food intake. The hypothalamus is sensitive to changes in the inflammatory state. Either high-grade inflammation (e.g., caused by sepsis) or low-grade inflammation (caused by obesity) disturbs the hypothalamic function via inflammatory cytokines. Understanding how these cytokines interact and regulate the circuits that control energy homeostasis is critical to understanding the pathophysiology of energy balance disorders. AgRP or POMC reporter mice were used to evaluate the acute electrical effects of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) on these neurons through whole-cell patch-clamp. Our results showed that 73% of AgRP cells were active and 27% quiescent during the recordings (n = 33 cells from 19 mice, 24 active and 9 quiescent). IL-6 (10 ng/ml) had no effect on theresting membrane potential (RPM) or membrane resistance(IR) of AgRP neurons. In contrast, TNF-α (20 ng/ml) induced a significant hyperpolarization in approximately 31.5% of registered cells (6 out of 21 neurons, change in RPM: – 9.8 ± 0.9 mV; P < 0.0001), although a non-significant reduction in the IR (P = 0.5) was observed. Regarding POMC neurons, we found that 61% of POMC cells were active and 39% quiescent during the recordings (n = 38 cells from 22 mice, 23 active and 15 quiescent cells). Both IL-6 and TNF-α had no significant effects on the electrical properties of POMC neurons. Therefore, these findings suggest that cytokines that are altered during sepsis or obesity may affect the activity of neuronal circuits that regulate energy balance. Additionally, the acute inhibitory effect of TNF-α on AgRP neuronal activity may explain the suppression in food intake observed during situations of high-grade inflammation.