Featured Research

from universities, journals, and other organizations

Obesity-related hormone discovered in fruit flies

Date:
September 27, 2012
Source:
Harvard Medical School
Summary:
Researchers have discovered in fruit flies a key metabolic hormone thought to be the exclusive property of vertebrates. The hormone, leptin, is a nutrient sensor, regulating energy intake and output and ultimately controlling appetite.

Three dimensional projection of the neuro-secretory region in the adult fly brain. High fat diets turn on signaling in inhibitory neurons (green) which in turn impinge on insulin producing neurons (purple).
Credit: Image by Akhila Rajan

Researchers have discovered in fruit flies a key metabolic hormone thought to be the exclusive property of vertebrates. The hormone, leptin, is a nutrient sensor, regulating energy intake and output and ultimately controlling appetite. As such, it is of keen interest to researchers investigating obesity and diabetes on the molecular level. But until now, complex mammals such as mice have been the only models for investigating the mechanisms of this critical hormone. These new findings suggest that fruit flies can provide significant insights into the molecular underpinnings of fat sensing.

"Leptin is very complex," said Akhila Rajan, first author on the paper and a postdoctoral researcher in the lab of Norbert Perrimon, James Stillman Professor of Developmental Biology at Harvard Medical School. "These types of hormones acquire more and more complex function as they evolve. Here in the fly we're seeing leptin in its most likely primitive form."

These findings will be published September 28 in Cell.

In order for an organism to function normally under varying conditions, its organ systems must learn to maintain a steady state, or "homeostasis." Coordinating food intake and nutrient stores with energy requirements is a key homeostatic mechanism referred to as energy homeostasis. Leptin regulates energy homeostasis by linking the organism's fat stores with caloric intake. It is the hormone that tells the brain, "You've had enough."

Researchers have known for the better part of a decade that molecules secreted by the fruit fly's fat tissue communicate such nutrition status reports throughout the fly's entire body. However, they have not known the identity of these molecules, or the nature of the signals they transmit. Rajan hypothesized that this signaling molecule most likely resembles the leptin hormone in humans, since flies and mammals share similar nutrient-sensing pathways.

Researchers had predicted that three molecules in flies were likely to be structurally similar to leptin. When Rajan knocked out one of them, a protein called Upd2, the flies behaved, on a metabolic level, as though they were starving -- despite consuming their normal caloric content.

"Since leptin is a nutrient sensor, this makes sense," said Rajan. "If you knock out the molecule that senses nutrients, the body thinks there are no nutrients. Blocking this molecule copied the phenotype of starvation."

Further tests showed that when flies were actually starving, levels of Upd2 went down, and when they received adequate nutrition, levels went up. This provided further evidence that, like leptin, Upd2 is a nutrient sensor.

Next, the researchers found that Upd2 uses a neural circuit similar to that of leptin to traffic nutrition information between the brain and fat tissue. When Upd2 reaches the brain, it regulates insulin secretion, in effect "telling" the fly to store nutrition and expend energy on growth.

Finally, Rajan and colleagues engineered a fly that lacked Upd2 altogether and inserted the human leptin gene in its place. The fly fully incorporated this mammalian molecule, and all normal nutrient-sensing functions resumed.

"The key significance here is that we can now take full advantage of the sophisticated genetic tool kit available in fly genetics to address profoundly complex questions pertaining to leptin biology," said Perrimon. "This is good news to scientists studying obesity at the molecular level."

Interestingly, the amino acid sequence of leptin diverges from that of Upd2. However, the proteins produced by each gene share many structural similarities. "There are very few examples of this in the literature," Perrimon said.

"Now that we've identified Upd2 as a fly's nutrient sensor and have begun to work out the brain circuitry, the next step is to go deep into the mechanisms," added Rajan.

This research was funded by the National Institutes of Health, grants 5P01CA120964 and 5R01DK088718.


Story Source:

The above story is based on materials provided by Harvard Medical School. The original article was written by David Cameron. Note: Materials may be edited for content and length.


Journal Reference:

  1. Akhila Rajan, Norbert Perrimon. Drosophila Cytokine Unpaired 2 Regulates Physiological Homeostasis by Remotely Controlling Insulin Secretion. Cell, 2012; 151 (1): 123 DOI: 10.1016/j.cell.2012.08.019

Cite This Page:

Harvard Medical School. "Obesity-related hormone discovered in fruit flies." ScienceDaily. ScienceDaily, 27 September 2012. <www.sciencedaily.com/releases/2012/09/120927124200.htm>.
Harvard Medical School. (2012, September 27). Obesity-related hormone discovered in fruit flies. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/2012/09/120927124200.htm
Harvard Medical School. "Obesity-related hormone discovered in fruit flies." ScienceDaily. www.sciencedaily.com/releases/2012/09/120927124200.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

Dangerous Bacteria Kills One in Florida

Dangerous Bacteria Kills One in Florida

AP (July 31, 2014) Sarasota County, Florida health officials have issued a warning against eating raw oysters and exposing open wounds to coastal and inland waters after a dangerous bacteria killed one person and made another sick. (July 31) Video provided by AP
Powered by NewsLook.com
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
Peace Corps Pulls Workers From W. Africa Over Ebola Fears

Peace Corps Pulls Workers From W. Africa Over Ebola Fears

Newsy (July 30, 2014) The Peace Corps is one of several U.S.-based organizations to pull workers out of West Africa because of the Ebola outbreak. Video provided by Newsy
Powered by NewsLook.com
Weather Kills 2K A Year, But Storms Aren't The Main Offender

Weather Kills 2K A Year, But Storms Aren't The Main Offender

Newsy (July 30, 2014) Health officials say 2,000 deaths occur each year in the U.S. due to weather, but it's excessive heat and cold that claim the most lives. 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