TY - JOUR
T1 - Endogenous Leptin Signaling in the Caudal Nucleus Tractus Solitarius and Area Postrema Is Required for Energy Balance Regulation
AU - Hayes, Matthew R.
AU - Skibicka, Karolina P.
AU - Leichner, Theresa M.
AU - Guarnieri, Douglas J.
AU - DiLeone, Ralph J.
AU - Bence, Kendra K.
AU - Grill, Harvey J.
N1 - Funding Information:
We thank Amber Alhadeff, Holly Greenwald, Hannah MacAyeal, and Derek Zimmer for technical assistance. This work was supported by National Institutes of Health-National Institute of Diabetes and Digestive and Kidney Diseases (NIH-NIDDK) grants DK21397 (H.J.G.), DK077484 (M.R.H.), and DK076964 (R.J.D); by the Institute of Diabetes, Obesity, and Metabolism at University of Pennsylvania (H.J.G.); and by The Obesity Society 2008 New Investigator Grant (M.R.H.).
PY - 2010/1/6
Y1 - 2010/1/6
N2 - Medial nucleus tractus solitarius (mNTS) neurons express leptin receptors (LepRs), and intra-mNTS delivery of leptin reduces food intake and body weight. Here, the contribution of endogenous LepR signaling in mNTS neurons to energy balance control was examined. Knockdown of LepR in mNTS and area postrema (AP) neurons of rats (LepRKD) via adeno-associated virus short hairpin RNA-interference (AAV-shRNAi) resulted in significant hyperphagia for chow, high-fat, and sucrose diets, yielding increased body weight and adiposity. The chronic hyperphagia of mNTS/AP LepRKD rats is likely mediated by a reduction in leptin potentiation of gastrointestinal satiation signaling, as LepRKD rats showed decreased sensitivity to the intake-reducing effects of cholecystokinin. LepRKD rats showed increased basal AMP-kinase activity in mNTS/AP micropunches, and pharmacological data suggest that this increase provides a likely mechanism for their chronic hyperphagia. Overall these findings demonstrate that LepRs in mNTS and AP neurons are required for normal energy balance control.
AB - Medial nucleus tractus solitarius (mNTS) neurons express leptin receptors (LepRs), and intra-mNTS delivery of leptin reduces food intake and body weight. Here, the contribution of endogenous LepR signaling in mNTS neurons to energy balance control was examined. Knockdown of LepR in mNTS and area postrema (AP) neurons of rats (LepRKD) via adeno-associated virus short hairpin RNA-interference (AAV-shRNAi) resulted in significant hyperphagia for chow, high-fat, and sucrose diets, yielding increased body weight and adiposity. The chronic hyperphagia of mNTS/AP LepRKD rats is likely mediated by a reduction in leptin potentiation of gastrointestinal satiation signaling, as LepRKD rats showed decreased sensitivity to the intake-reducing effects of cholecystokinin. LepRKD rats showed increased basal AMP-kinase activity in mNTS/AP micropunches, and pharmacological data suggest that this increase provides a likely mechanism for their chronic hyperphagia. Overall these findings demonstrate that LepRs in mNTS and AP neurons are required for normal energy balance control.
UR - http://www.scopus.com/inward/record.url?scp=72649103549&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=72649103549&partnerID=8YFLogxK
U2 - 10.1016/j.cmet.2009.10.009
DO - 10.1016/j.cmet.2009.10.009
M3 - Article
C2 - 20074530
AN - SCOPUS:72649103549
SN - 1550-4131
VL - 11
SP - 77
EP - 83
JO - Cell Metabolism
JF - Cell Metabolism
IS - 1
ER -