Neurons in the dorsomedial hypothalamus (DMH) are required for leptin‐induced activation of brown adipose tissue (BAT) thermogenesis

Abstract

The increased sympathetic nerve activity (SNA) to BAT stimulated by intravenous (iv) administration of leptin was inhibited by microinjection of the 5-HT1A receptor agonist, 8-OH-DPAT, into the raphe pallidus (RPa), indicating that neurons in RPa, presumably BAT sympathetic premotor neurons, are required for leptin-induced activation of BAT thermogenesis. In present study, we tested the hypothesis that DMH neurons comprised a requisite synaptic link in the central neural pathway for leptin-induced BAT thermogenesis. In six anesthetized rats maintained at a core temperature of 35.5°C, iv administration of leptin (1.0 mg/kg) increased BAT SNA by +4635% of control, BAT temperature by +3.0°C as well as RSNA by +164% of control. Subsequent inhibition of DMH neurons by microinjection of glycine (0.5 M/60 nl) reversed the leptin-induced BAT thermogenesis, but had no effect on the leptin-induced increase in RSNA. Similarly, intracerebroventricular (icv) administration of leptin (10μg/10μl) increased BAT SNA by 3516% of control, BAT temperature by +2.3°C and RSNA by +154% of control at a core temperature of 36.1°C. Icv leptin-induced increases in BAT SNA and BAT thermogenesis, but not those in RSNA, were reversed by subsequent bilaterally microinjection of muscimol (2 mM/60 nl) into the DMH. These results indicate that the increased energy expenditure in BAT by stimulation of central leptin receptors requires activation of neurons in the DMH and that the leptin-evoked stimulation of renovascular function uses a sympathoexcitatory pathway that does not include DMH neurons. Supported by NIH DK57838 and DK20378.