Hypothalamic ERK mediates the anorectic and thermogenic sympathetic effects of leptin. Diabetes 2009 Mar;58(3):536-42
Date
12/11/2008Pubmed ID
19066310Pubmed Central ID
PMC2646051DOI
10.2337/db08-0822Scopus ID
2-s2.0-62749109421 (requires institutional sign-in at Scopus site) 168 CitationsAbstract
OBJECTIVE: Leptin is an adipocyte hormone that plays a major role in energy balance. Leptin receptors in the hypothalamus are known to signal via distinct mechanisms, including signal transducer and activator of transcription-3 (STAT3) and phosphoinositol-3 kinase (PI 3-kinase). Here, we tested the hypothesis that extracellular signal-regulated kinase (ERK) is mediating leptin action in the hypothalamus.
RESEARCH DESIGN AND METHODS: Biochemical, pharmacological, and physiological approaches were combined to characterize leptin activation of ERK in the hypothalamus in rats.
RESULTS: Leptin activates ERK1/2 in a receptor-mediated manner that involves JAK2. Leptin-induced ERK1/2 activation was restricted to the hypothalamic arcuate nucleus. Pharmacological blockade of hypothalamic ERK1/2 reverses the anorectic and weight-reducing effects of leptin. The pharmacological antagonists of ERK1/2 did not attenuate leptin-induced activation of STAT3 or PI 3-kinase. Blockade of ERK1/2 abolishes leptin-induced increases in sympathetic nerve traffic to thermogenic brown adipose tissue (BAT) but does not alter the stimulatory effects of leptin on sympathetic nerve activity to kidney, hindlimb, or adrenal gland. In contrast, blockade of PI 3-kinase prevents leptin-induced sympathetic activation to kidney but not to BAT, hindlimb, or adrenal gland.
CONCLUSIONS: Our findings indicate that hypothalamic ERK plays a key role in the control of food intake, body weight, and thermogenic sympathetic outflow by leptin but does not participate in the cardiovascular and renal sympathetic actions of leptin.
Author List
Rahmouni K, Sigmund CD, Haynes WG, Mark ALAuthor
Curt Sigmund PhD Chair, Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adipose Tissue, BrownAnimals
Body Weight
Energy Intake
Extracellular Signal-Regulated MAP Kinases
Hypothalamus
Injections, Intraperitoneal
Injections, Intraventricular
Leptin
Male
Mice
Neurons
Paraventricular Hypothalamic Nucleus
Rats
Rats, Sprague-Dawley
Rats, Zucker
Receptors, Leptin
Sympathetic Nervous System
