Featured Research

from universities, journals, and other organizations

New Information About How Fat Increases Blood Pressure Could Help Identify Those At Risk

Date:
September 3, 2009
Source:
Medical College of Georgia
Summary:
Some of the first information about how fat causes hypertension have been identified by researchers who say the findings should one day help identify which obese people -- and maybe some thin ones too -- are at risk for hypertension and which drugs would work best for them.

Dr. David Stepp, MCG vascular biologist with Dr. Eric J. Belin de Chamtem่le, a postdoctoral fellow in his lab.
Credit: Medical College of Georgia

Some of the first information about how fat causes hypertension have been identified by researchers who say the findings should one day help identify which obese people – and maybe some thin ones too – are at risk for hypertension and which drugs would work best for them.

Medical College of Georgia researchers have found that deleting or mutating the gene PTP1B puts mice at risk for hypertension by interfering with an endogenous mechanism that should help prevent it. The findings are published in the Sept. 1 issue of the American Heart Association journal Circulation.

"In a normal individual gaining weight, PTP1B should increase and they would be protected in theory from hypertension," says Dr. David Stepp, vascular biologist at the MCG Vascular Biology Center, co-director of the Diabetes & Obesity Discovery Institute and the study's corresponding author.

"But if you don't have a good copy of PTP1B and you become obese, then you are going to have a problem. So in theory this gene can segregate the obese people who will become hypertensive and those who won't."

Knowing the gene's status could also one day help physicians better select an antihypertensive medication for those who do.

A key player is the hormone leptin, produced by fat cells. Overweight individuals generally produce more of the hormone that essentially revs up the body, suppressing appetite and increasing metabolism so you won't get fatter. But leptin also increases blood pressure by activating the sympathetic nervous system, the so-called fight-or-flight response. Mutated or missing PTP1B dramatically increases leptin's negative effects.

MCG scientists studying how blood pressure got the message to increase found leptin also provides protection against high pressures by turning off the signaling pathway that squeezes blood vessels and drive pressures up in a process called adrenergic desensitization.

"Normally, if you give someone leptin, his blood pressure would probably not go up because he would have this protective mechanism intact that would basically turn off his blood pressure signaling pathway," Dr. Stepp says. "His blood pressure would be regulated differently, but it would not be high."

But the combination of missing or mutated PTP1B and too much leptin means increases in constriction are too strong to turn off.

Mice missing PTP1B tend to have lower body fat but high blood pressure, not usually what you see in people, Dr. Stepp notes. While this single gene can't explain every combination of body size and blood pressure found in nature, it could help explain why some skinny people are hypertensive and why others who get fat are as well.

"It's a vulnerability gene," he says. "If you stimulate leptin in individuals who can't activate their protective mechanisms, they are going to get hypertension. This tells us there are a lot of people and diseases

And what about those people who have great blood pressure? They likely have well-functioning PTP1B, he notes. Interestingly, PTP1B often is over expressed in obese people, which is good for the blood pressure but bad for leptin's positive effect on metabolism.

"I think we have identified at least a couple of new pieces of information that clarify the relationship between obesity and hypertension," Dr. Stepp says. "We have identified a gene that, if it's not functional, will greatly increase the extent to which a metabolic signal from leptin translates into a cardiovascular signal. We also have identified a protective mechanism that, if it's not working, contributes to hypertension."

The MCG research helps illustrate the need to pay particular attention to the cardiovascular side effects of potential new anti-obesity drugs as well, experts say. In an accompany editorial, Dr. Allyn L. Mark, Carver Professor of Medicine, Center on Functional Genomics of Hypertension at the University of Iowa Carver College of Medicine, noted the irony that despite lower body fat, mice with disturbed PTP1B had higher blood pressure than control animals. "Unfortunately several of the interventions that inhibit appetite, increase metabolism and decrease adiposity (fat) may increase (not decrease) sympathetic activity and arterial pressure," he writes. "This may complicate the safety of potential anti-obesity drugs," and emphasizes the importance of evaluating the cardiovascular impact of potential new therapies.

Now MCG scientists want to develop markers so one day people determine their PTP1B expression through a blood test. They also want to learn more about exactly how leptin increases blood pressure to see if there are ways to target some of the downstream impact of missing or mutated PTP1B.

"We want to look the impact on the kidneys and angiotensin 2," says Dr. Eric J. Belin de Chamtem่le, postdoctoral fellow in Dr. Stepp's lab and the study's first author. The kidneys, which determine how much sodium and water are excreted from the body, are major players in blood pressure regulation. Renin, which is secreted by the kidneys, constricts blood vessels to help blood pressure increase when blood volume gets low.

They want to know if leptin is acting directly on the kidneys or whether it's an indirect result from leptin's action in the brain. They suspect it's primarily a brain effect that they want to pursue by using mice with leptin deficits localized to the brain.


Story Source:

The above story is based on materials provided by Medical College of Georgia. The original article was written by Toni Baker. Note: Materials may be edited for content and length.


Cite This Page:

Medical College of Georgia. "New Information About How Fat Increases Blood Pressure Could Help Identify Those At Risk." ScienceDaily. ScienceDaily, 3 September 2009. <www.sciencedaily.com/releases/2009/09/090901104852.htm>.
Medical College of Georgia. (2009, September 3). New Information About How Fat Increases Blood Pressure Could Help Identify Those At Risk. ScienceDaily. Retrieved September 17, 2014 from www.sciencedaily.com/releases/2009/09/090901104852.htm
Medical College of Georgia. "New Information About How Fat Increases Blood Pressure Could Help Identify Those At Risk." ScienceDaily. www.sciencedaily.com/releases/2009/09/090901104852.htm (accessed September 17, 2014).

Share This



More Health & Medicine News

Wednesday, September 17, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

President To Send 3,000 Military Personnel To Fight Ebola

President To Send 3,000 Military Personnel To Fight Ebola

Newsy (Sep. 16, 2014) — President Obama is expected to send 3,000 troops to West Africa as part of the effort to contain Ebola's spread. Video provided by Newsy
Powered by NewsLook.com
Obama Orders Military Response to Ebola

Obama Orders Military Response to Ebola

AP (Sep. 16, 2014) — Calling the Ebola outbreak in West Africa a potential threat to global security, President Barack Obama is ordering 3,000 U.S. military personnel to the stricken region amid worries that the outbreak is spiraling out of control. (Sept. 16) Video provided by AP
Powered by NewsLook.com
UN: 20,000 Could Be Infected With Ebola by Year End

UN: 20,000 Could Be Infected With Ebola by Year End

AFP (Sep. 16, 2014) — Nearly $1.0 billion dollars is needed to fight the Ebola outbreak raging in west Africa, the United Nations say, warning that 20,000 could be infected by year end. Duration: 00:40 Video provided by AFP
Powered by NewsLook.com
Obama: Ebola Outbreak Threat to Global Security

Obama: Ebola Outbreak Threat to Global Security

AP (Sep. 16, 2014) — President Obama is ordering U.S. military personnel to West Africa to deal with the Ebola outbreak, which is he calls a potential threat to global security. (Sept. 16) Video provided by AP
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