Navigation Links
Modulation of inhibitory output is key function of antiobesity hormone
Date:7/13/2011

Scientists have known for some time that the hormone leptin acts in the brain to prevent obesity, but the specific underlying neurocircuitry has remained a mystery. Now, new research published by Cell Press in the July 14 issue of the journal Neuron reveals neurobiological mechanisms that may underlie the antiobesity effects of leptin.

"Leptin is a hormone that is secreted by fat cells and acts at its receptor in the brain to decrease food intake and promote energy expenditure," explains senior study author Dr. Bradford B. Lowell from Beth Israel Deaconess Medical Center and Harvard Medical School. "However, despite intensive investigation, the underlying mechanisms responsible for this are poorly understood, in part due to incomplete knowledge regarding leptin-responsive neurons."

Previous studies by Dr. Lowell's group and others pinpointed a region of the brain called the arcuate nucleus as the site of key components related to the control of obesity. In particular, pro-opiomelanocortin (POMC) neurons, which have been shown to play a key role in appetite suppression, reside in this region. Although many POMC neurons express receptors for leptin, direct action of leptin on POMC neurons has not been shown to play a large role in controlling body weight. This suggests that there are likely to be other leptin-responsive neurons that are critical for leptin's antiobesity actions.

In the current study, Dr. Lowell and colleagues took a new approach for identifying these "unidentified" body weight-regulating neurons and investigated whether leptin's effects are mediated primarily by excitatory (glutamate) or inhibitory (GABA) neurons. "Remarkably, we found that leptin's antiobesity effects are mediated predominantly by GABA neurons and that glutamate neurons play only a small role," says Dr. Linh Vong, a first author on the study. Importantly, the GABA neurons are "upstream" of the POMC neurons and, in response to leptin, the GABA neurons are less active. Conversely, a reduction in leptin levels, such as occurs with fasting, increases the activity of these GABA neurons.

Taken together, the findings suggest that modulation of GABA output is a key aspect of leptin action. "Leptin working directly on GABA neurons reduces inhibitory tone to POMC neurons," concludes Dr. Lowell. "As POMC neurons prevent obesity, their disinhibition by leptin action on upstream GABA neurons likely mediates, at least in part, leptin's antiobesity effects. Further, indirect regulation of POMC neurons by leptin reconciles the known important role of POMC neurons in regulating body weight with the relatively unimportant role played by direct action of leptin on POMC neurons."


'/>"/>

Contact: Elisabeth (Lisa) Lyons
elyons@cell.com
617-386-2121
Cell Press
Source:Eurekalert

Related biology technology :

1. Neurologix Presents One-Year Follow-Up Data From Phase 2 Study of NLX-P101 in Parkinsons Disease at International Neuromodulation Society 10th World Congress
2. Victhom Human Bionics Receives CE Mark for the Neurostep(TM) System, the Worlds First Fully Implantable Closed-Loop Neuromodulation Therapy for Treatment of Foot Drop
3. Chinas Research Output More Than Doubled Since 2004, Thomson Reuters Study Reveals
4. Despite Decline in Share of Global Output, U.S. Science Impact Still Strong, Says Thomson Reuters
5. Molecular Devices Enables Intuitive Functionality at Your Fingertips on the Apple iPad with the Latest SoftMax Pro Software
6. Rhythms RM-131 Restores GI Function as a Potent Ghrelin Prokinetic
7. Functional Nutriments Awarded Federal Grant to Apply Its Dog Nutraceutical Research to Human Cancer
8. Creating Functional Hepatic Tissue in a Bioengineered Human Liver
9. Tengion Presents New Large Animal Data Demonstrating Functional Kidney Regeneration at the American Society for Transplantation Annual Conference
10. NephRx Corp. Receives Orphan Drug Designation for NX001 for Prevention of Delayed Kidney Graft Function
11. Prostate cancer risk variant found to be in a functional DNA sequence linked with disease
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/27/2016)... NC (PRWEB) , ... June 27, 2016 , ... ... mission to bring innovative medical technologies, services and solutions to the healthcare market. ... and implementation of various distribution, manufacturing, sales and marketing strategies that are necessary ...
(Date:6/24/2016)... June 24, 2016 Epic Sciences unveiled ... cancers susceptible to PARP inhibitors by targeting homologous ... (CTCs). The new test has already been incorporated ... multiple cancer types. Over 230 clinical ... response pathways, including PARP, ATM, ATR, DNA-PK and ...
(Date:6/23/2016)... , June 23, 2016   Boston ... of novel compounds designed to target cancer stemness ... has been granted Orphan Drug Designation from the ... treatment of gastric cancer, including gastroesophageal junction (GEJ) ... inhibitor designed to inhibit cancer stemness pathways by ...
(Date:6/23/2016)... 23, 2016  The Prostate Cancer Foundation (PCF) is pleased to ... faster cures for prostate cancer. Members of the Class of 2016 were selected ... Read More About the Class of 2016 PCF Young Investigators ... ... ...
Breaking Biology Technology:
(Date:6/21/2016)... , June 21, 2016 NuData ... the new role of principal product architect and ... the director of customer development. Both will report ... technical officer. The moves reflect NuData,s strategic growth ... response to high customer demand and customer focus ...
(Date:6/9/2016)... 9, 2016  Perkotek an innovation leader in attendance control systems is proud to ... hours, for employers to make sure the right employees are actually signing in, and ... ... ... ...
(Date:6/2/2016)... 2, 2016 The Department of Transport ... the 44 million US Dollar project, for the , ... including Personalization, Enrolment, and IT Infrastructure , to ... production and implementation of Identity Management Solutions. Numerous renowned international ... Decatur was selected for the most compliant ...
Breaking Biology News(10 mins):