Loss of histaminergic modulation of thermoregulation and energy homeostasis in obese mice

Abstract

Histamine acts centrally to increase energy expenditure and reduce body weight by mechanisms not fully understood. It has been suggested that in the obese state hypothalamic histamine signaling is altered. Previous studies have also shown that histamine acting in the preoptic area controls thermoregulation. We aimed to study the influence of preoptic histamine on body temperature and energy homeostasis in control and obese mice. Activating histamine receptors in the preoptic area by increasing the concentration of endogenous histamine or by local injection of specific agonists induced an elevation of core body temperature and decreased respiratory exchange ratio (RER). In addition, the food intake was significantly decreased. The hyperthermic effect was associated with a rapid increase in mRNA expression of uncoupling proteins in thermogenic tissues, the most pronounced being that of uncoupling protein (UCP) 1 in brown adipose tissue and of UCP2 in white adipose tissue. In diet induced obese mice histamine had much diminished hyperthermic effects as well as reduced effect on RER. Similarly, the ability of preoptic histamine signaling to increase the expression of uncoupling proteins was abolished. We also found that the expression of mRNA encoding the H1 receptor subtype in the preoptic area was significantly lower in obese animals. These results indicate that histamine signaling in the preoptic area modulates energy homeostasis by regulating body temperature, metabolic parameters and food intake and that the obese state is associated with a decrease in neurotransmitter’s influence.

Ameliorating antipsychotic-induced weight gain by betahistine: Mechanisms and clinical implications

“…In particular, histamine has been implicated in the regulation of energy homeostasis [12,43,44]. In other words, elevated hypothalamic histamine signalling contributed to decreased food intake and decreased body weight gain [45][46][47]35], while reduction in histamine levels was associated with increased body weight gain and food intake [37,42].…”

The Role of Hypothalamic H1 Receptor Antagonism in Antipsychotic-Induced Weight Gain

“…[39] Studies also suggest that activation of H1 receptors expressed on glutamatergic neurons in the MnPO activates BAT thermogenesis by stimulating sympathetic neurons in the rRPa. [39,41] Additionally, in the medial preoptic nucleus (MPON), H1 receptor activation on the glutamatergic neurons also significantly regulates body temperature, although H2…”

Histaminergic Modulation of Body Temperature and Energy Expenditure

“…Our studies have established that in mice histamine induces hyperthermia when administered in either the medial or the median preoptic nuclei [59]. Similarly, when the endogenous concentration of histamine was raised in either nucleus by local injection of histamine N-methyl transferase inhibitor a hyperthermia of similar amplitude was observed [59].…”

“…Similarly, when the endogenous concentration of histamine was raised in either nucleus by local injection of histamine N-methyl transferase inhibitor a hyperthermia of similar amplitude was observed [59]. H1R and H3R specific agonists were equally potent in inducing a hyperthermia when infused in the median preoptic nucleus [21].…”

“…In our study [59] we have determined the effects of activation of histamine receptors in the preoptic area by increasing the concentration of endogenous histamine or by local injection of specific agonists. Both approaches induce an elevation of core body temperature and decreased respiratory exchange ratio (RER).…”