Abstract
Leptin is a hormone released from adipose tissue. While this hormone normally acts to reduce feeding behavior and increase energy expenditure, in obesity, resistance to these effects occurs even though the hormone is released in large amounts. Although leptin no longer works to suppress feeding in the obese, leptin retains its potent effects on other autonomic functions such as blood pressure regulation. Leptin has been associated with hypertension and increased sympathetic autonomic activity. Therefore, leptin is emerging as a major contributor to the hypertensive state observed in obesity. Sympathetic control of blood pressure is maintained principally by autonomic reflex control circuits in the caudal brainstem. The rostral ventral-lateral medulla (RVLM) is the primary regulator of the sympathetic nervous system, sending excitatory fibers to sympathetic preganglionic neurons to regulate sympathetic control over resistance vessels and blood pressure. Previous studies from our laboratory have shown that neurons in the ventral lateral medulla express leptin receptors (ObRb). Our present study using pseudo-rabies multi-synaptic retrograde tract tracing and immunohistochemical methods revealed that neurons within the RVLM that send sympathetic projections to the kidney express leptin receptors. Acute microinjection of leptin (1 and 3 μg; 40 nL) into the RVLM evoked a significant increase in Mean Arterial Pressure (MAP) and renal sympathetic nerve activity (RSNA). When the 3 μg dose of leptin was preceded with a leptin antagonist, (SLAN-4; 1 ng), it attenuated the cardiovascular response of leptin. Taken together, these data suggest that leptin's actions within the RVLM may influence blood pressure and renal sympathetic nerve activity.
Highlights
Leptin is an adipocyte-derived hormone which signals the availability of peripheral energy stores
HISTOLOGY ObRb positive cells in the ventral medulla were found in the C1/A1 cell group and the ventromedial region Cells in the ventral hindbrain that were positive for ObRb staining were localized in one of four regions: the C1/A1 cell column, ventromedial medulla (VMM), caudal raphe, and A5 cell group
An average of 420 ± 87 ObRb+ cells were observed in C1/A1, 146 ± 32 ObRb+ cells were observed in VMM, 107 ± 87 ObRb+ cells were observed in A5, and 26 ± 14 ObRb+ cells were observed in the caudal raphe (Table 1)
Summary
Leptin is an adipocyte-derived hormone which signals the availability of peripheral energy stores. Circulating leptin levels act as a long term signal of the amount of fat stored in white adipose tissue, while short term fluctuations in leptin levels convey information regarding acute changes in caloric intake This information is integrated centrally by the autonomic nervous system to regulate a variety of homeostatic functions, most notably food intake and energy expenditure (Morris and Rui, 2009; Myers et al, 2009; Galic et al, 2010; Kelesidis et al, 2010). Leptin regulates blood pressure via augmentation of renal sympathetic nerve activity (RSNA); events which are believed to play a significant role in the development of hypertension (Hall et al, 2010). This change in RSNA and blood pressure after leptin administration is absent in experimental animals that have defective leptin receptors (i.e., Zucker Rats and db/db mice), suggesting that these effects are leptin receptor mediated (Haynes et al, 1997; Rahmouni et al, 2003)
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