Endogenous peripheral hydrogen sulfide is propyretic: its permissive role in brown adipose tissue thermogenesis in rats

Abstract

New Findings: What is the central question of this study? In fever, the most striking response in the acute phase reaction of systemic inflammation, plasma H2S concentration increases. However, the role of endogenous peripheral H2S in fever is unknown. What is the main finding and its importance? Endogenous peripheral H2S is permissive for increased brown adipose tissue thermogenesis to maintain thermal homeostasis in cold environments as well as to mount fever. This finding expands the physiological role of the gaseous modulator as a key regulator of thermal control in health (thermal homeostasis) and disease (fever in systemic inflammation). Abstract: In recent years, hydrogen sulfide (H2S) has been reported as a gaseous modulator acting in several tissues in health and disease. In animal models of systemic inflammation, the plasma H2S concentration increases in response to endotoxin (bacterial lipopolysaccharide, LPS). The most striking response in the acute phase reaction of systemic inflammation is fever, but we found no reports of the peripheral action of H2S on this thermoregulatory response. We aimed at investigating whether endogenous systemic H2S modulates LPS-induced fever. A temperature datalogger capsule was inserted in the abdominal cavity of male Wistar rats (220–270 g) to record body core temperature. These animals received an i.p. injection of a systemic H2S inhibitor (propargylglycine; 50 or 75 mg kg−1), immediately followed by an i.p. injection of LPS (50 or 2500 μg kg−1), and were exposed to different ambient temperatures (16, 22 or 27°C). At 22°C, but not at 27°C, propargylglycine at 75 mg kg−1 significantly attenuated (P < 0.0001) the fever induced by LPS (50 μg kg−1), indicating a modulatory (permissive) action of endogenous peripheral H2S on brown adipose tissue (BAT) thermogenesis. Evidence on the modulatory role of peripheral H2S in BAT thermogenesis was strengthened when we discarded (i) the possible influence of the gas on febrigenic signalling (when measuring plasma cytokines), and (ii) its interaction with the nitric oxide pathway, and mainly when (iii) we carried out physiological and pharmacological activations of BAT. Endogenous peripheral H2S modulates (permits) BAT activity not only in fever but also during maintenance of thermal homeostasis in cold environments.