Featured Research

from universities, journals, and other organizations

Leptin's Role In Brain Neurocircuitry Clarified

Date:
June 3, 2009
Source:
Beth Israel Deaconess Medical Center
Summary:
New findings demonstrate that leptin's influence on tiny group of POMC neurons restores blood sugar control -- and spontaneously increases physical activity levels -- in an animal model of severe, insulin-resistant diabetes.

In investigating the complex neurocircuitry behind weight gain and glucose control, scientists have known that the hormone leptin plays a key role in the process. But within the myriad twists and turns of the brain's intricate landscape, the exact pathways that the hormone travels to exert its influence have remained a mystery.

Now, a study led by investigators at Beth Israel Deaconess Medical Center (BIDMC) sheds further light on the subject. Reported in tomorrow's issue of the journal Cell Metabolism, the findings demonstrate that when leptin sensitivity is restored to a tiny area of POMC neurons in the brain's hypothalamus, a group of mice deficient in the leptin-receptor are cured of severe diabetes – and also spontaneously double their activity levels – independent of any change in weight or eating habits.

"This discovery suggests a new therapeutic pathway for drugs to treat insulin-resistant diabetes in humans with severe obesity, and possibly even to stimulate their urge to exercise," explains Christian Bjorbaek, PhD, an investigator in the Division of Endocrinology, Diabetes and Metabolism at BIDMC and Associate Professor of Medicine at Harvard Medical School. "We know that the majority of humans with Type 2 diabetes are obese and that weight loss can often ameliorate the disease. However, in many cases, it's difficult for these individuals to lose weight and can keep weight off. If, as these findings suggest, there is a system in the brain that can control blood-glucose directly, it offers hope for the identification of novel anti-diabetic drug targets."

First identified in 1994 as an appetite and weight-regulation hormone, leptin plays a key role in energy homeostasis through its effects on the central nervous system. Over the years, investigators have pinpointed a region of the brain's hypothalamus known as the arcuate nucleus (ARC) as one key area where leptin exerts its influence, and within the ARC, they have identified two types of leptin-responsive neurons, the Agouti-related peptide (AgRP) neurons, which stimulate appetite and the pro-opiomelanocortin (POMC) neurons, which curb appetite.

"Still other studies had indicated that, by way of the ARC, leptin also had a function in both blood-sugar control and in activity levels," notes Bjorbaek. "We hypothesized that, in both cases, the POMC neurons were involved."

To test their hypothesis, the scientists studied a group of leptin-receptor-deficient laboratory mice. "The animals were severely obese and profoundly diabetic," he explains. "Using Cre-Lox technology we were able to genetically and selectively re-express leptin receptors only in the POMC neurons. When leptin receptor activity was restored to just this very small group of neurons, the mice began eating about 30 percent fewer calories and lost a modest amount of weight." And, he adds, even more dramatically, the animals' blood sugar levels returned to normal independent of any change in weight or eating habits, and their activity levels spontaneously doubled.

While more research is needed to explain the mechanisms at play, it may be that the POMC neurons reduce blood glucose by regulating key organs such as the liver or muscle tissue. "Normally, the liver is critical for increasing glucose production between meals in order to provide fuel for the brain, while skeletal muscle is important for the removal of glucose from the blood immediately after a meal," he notes. In this case, however, the POMC neurons may be decreasing glucose release into the blood by the liver and/or increasing glucose uptake from the blood into muscle.

"The fact that normal glucose levels were restored independent of food or weight changes is important because it suggests that it is possible to normalize blood glucose even without weight loss," explains Bjorbaek. "Furthermore, our finding that the mice had greatly increased activity levels despite still being highly overweight provides hope that POMC neurons and downstream neuronal systems might eventually be tapped to develop drugs that increase the will to voluntarily exercise in individuals who are overweight or obese."

Study coauthors include BIDMC researchers Lihong Huo (first author), Kevin Gamber, Sarah Greeley, Jose Silva and Nicholas Huntoon and Xing-Hong Leng of Baylor College of Medicine, Houston, Texas.

This study was funded by grants from the American Diabetes Association, the Richard and Susan Smith Family Foundation Pinnacle Program Project, the National Institutes of Health, the Endocrine Society, and the Boston Obesity Nutrition Research Center.


Story Source:

The above story is based on materials provided by Beth Israel Deaconess Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

Beth Israel Deaconess Medical Center. "Leptin's Role In Brain Neurocircuitry Clarified." ScienceDaily. ScienceDaily, 3 June 2009. <www.sciencedaily.com/releases/2009/06/090602133553.htm>.
Beth Israel Deaconess Medical Center. (2009, June 3). Leptin's Role In Brain Neurocircuitry Clarified. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/2009/06/090602133553.htm
Beth Israel Deaconess Medical Center. "Leptin's Role In Brain Neurocircuitry Clarified." ScienceDaily. www.sciencedaily.com/releases/2009/06/090602133553.htm (accessed July 31, 2014).

Share This




More Health & Medicine News

Thursday, July 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
Concern Grows Over Worsening Ebola Crisis

Concern Grows Over Worsening Ebola Crisis

AFP (July 30, 2014) Pan-African airline ASKY has suspended all flights to and from the capitals of Liberia and Sierra Leone amid the worsening Ebola health crisis, which has so far caused 672 deaths in Guinea, Liberia and Sierra Leone. Duration: 00:43 Video provided by AFP
Powered by NewsLook.com
At Least 20 Chikungunya Cases in New Jersey

At Least 20 Chikungunya Cases in New Jersey

AP (July 30, 2014) At least 20 New Jersey residents have tested positive for chikungunya, a mosquito-borne virus that has spread through the Caribbean. (July 30) Video provided by AP
Powered by NewsLook.com
Xtreme Eating: Your Daily Caloric Intake All On One Plate

Xtreme Eating: Your Daily Caloric Intake All On One Plate

Newsy (July 30, 2014) The Center for Science in the Public Interest released its 2014 list of single meals with whopping calorie counts. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

    Environment News

    Technology News



      Save/Print:
      Share:

      Free Subscriptions


      Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

      Get Social & Mobile


      Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

      Have Feedback?


      Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
      Mobile: iPhone Android Web
      Follow: Facebook Twitter Google+
      Subscribe: RSS Feeds Email Newsletters
      Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins