Sympathetic and cardiorenal actions of leptin.
Body weight is tightly regulated physiologically. The recent discovery of the peptide hormone leptin has permitted more detailed evaluation of the mechanisms responsible for control of body fat. Leptin is almost exclusively produced by adipose tissue and acts in the CNS through a specific receptor and multiple neuropeptide pathways to decrease appetite and increase energy expenditure. Leptin thus functions as the afferent component of a negative feedback mechanism to control adipose tissue mass. Increasing evidence suggests that leptin may have wider actions influencing autonomic, cardiovascular, and endocrine function. Intravenous leptin increases norepinephrine turnover and sympathetic nerve activity to thermogenic brown adipose tissue. Studies from our laboratory suggest that leptin also increases sympathetic nerve activity to kidney, hindlimb, and adrenal gland. However, systemic administration of leptin does not acutely increase arterial pressure or heart rate in anesthetized animals. Thus, longer-term exposure to hyperleptinemia may be necessary for full expression of the expected pressor effect of renal sympathoexcitation. Alternatively, leptin may have additional cardiovascular actions to oppose sympathetically mediated vasoconstriction. Leptin in high doses increases renal sodium and water excretion, apparently through a direct tubular action. In addition, leptin appears to increase systemic insulin sensitivity, even in the absence of weight loss. Although we are at an early stage of understanding, we speculate that abnormalities in the actions of leptin may have implications for the sympathetic, cardiovascular, and renal changes associated with obesity.
Haynes
W G
WG
Hypertension Genetics Specialized Center of Research, and Department of Internal Medicine, University of Iowa College of Medicine and Veterans Affairs Medical Center, Iowa City 52242, USA. william-g-haynes@uiowa.edu
Sivitz
W I
WI
Morgan
D A
DA
Walsh
S A
SA
Mark
A L
AL
D000273:Adipose Tissue / Q000187:drug effects; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007668:Kidney / Q000187:drug effects*; D020738:Leptin; D009765:Obesity / Q000503:physiopathology; D011506:Proteins / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000187:drug effects*
D007328:Insulin; D020738:Leptin; D011506:Proteins