Abstract
Obesity-associated low-grade inflammation favors weight gain, whereas systemic infection frequently leads to anorexia. Thus, inflammatory signals can either induce positive or negative energy balance. In this study, we used whole-cell patch-clamp to investigate the acute effects of three important proinflammatory cytokines, tumor necrosis factor α (TNF-α), interleukin-6, and interleukin-1β (IL-1β) on the membrane excitability of agouti-related peptide (AgRP)- or proopiomelanocortin (POMC)-producing neurons. We found that both TNF-α and IL-1β acutely inhibited the activity of 35–42% of AgRP-producing neurons, whereas very few POMC neurons were depolarized by TNF-α. Interleukin-6 induced no acute changes in the activity of AgRP or POMC neurons. Our findings indicate that the effect of TNF-α and IL-1β, especially on the activity of AgRP-producing neurons, may contribute to inflammation-induced anorexia observed during acute inflammatory conditions.
Highlights
The hypothalamus is a brain structure responsible for the regulation of numerous visceral functions, including the control of body temperature, autonomic nervous system, and feeding behavior, among others [1]
The objective of the present study was to investigate the acute effects induced by tumor necrosis factor α (TNF-α), IL-6, and IL-1β on the resting membrane potential (RMP) and input resistance (IR) of agouti-related peptide (AgRP)/neuropeptide Y (NPY) and POMC neurons in the ARH
In contrast to the effects caused by TNF-α administration, we found that IL-6 did not significantly change the RMP and IR of either active (Figure 2A) or quiescent (Figure 2B) AgRP neurons
Summary
The hypothalamus is a brain structure responsible for the regulation of numerous visceral functions, including the control of body temperature, autonomic nervous system, and feeding behavior, among others [1]. Several hypothalamic nuclei are involved in the central control of metabolism, even though a well-characterized population is composed of neurons located in the ventral aspects of the third ventricle. In rodents, this area is called the arcuate nucleus (ARH) and is composed of several neurochemically defined neuronal populations [4,5,6,7]. In the ventromedial aspects of the ARH, there is a great number of neurons co-expressing agouti-related peptide (AgRP) and neuropeptide Y (NPY) [8]. AgRP/NPY-producing neurons are powerful inducers of hunger, and their activation leads to weight gain [9,10]. In contrast to AgRP/NPY-expressing cells, POMC neurons generally promote satiety [13,14]
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