What Causes Obesity?


The following news report discusses the apparent effect of C-Reactive Protein (CRP), a blood protein indicating systemic inflammation, and Leptin, a hormone that signals satiety (feeling full and satisfied).  Researchers believe there may be an association between inflammation and obesity.

Leptin is secreted by fat cells, and the more fat, the more leptin.  In the  hypothalamus region of the brain, leptin binds to receptors which signal the brain to stop eating and the body to expend energy by burning calories. Obese people produce high levels of leptin, but are somehow resistant to leptin's effects.  Researchers believe the binding of CRP to leptin may be one reason for this leptin resistance.

Other research reports higher levels of CRP in the blood of people with diarrhea associated Functional Bowel Disorders  http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=PubMed. Irritable Bowel Syndrome (IBS) is one such disorder often associated with diarrhea.  IBS has been reported to be associated with increased intestinal permeability or "leaky gut syndrome"
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15606393&dopt=Abstract

The increased permeability of leaky gut syndrome allows toxic materials (undigested foods, bacteria, toxins, parasites, etc.) to enter the blood where they don't belong.  This in turn causes activation of the immune system.  http://www.ibdanswers.com/AppA-ClinicalDefinitionOfLeakyGutSyndrome.  Production of CRP may be part of the immune activation in leaky gut syndrome..

Additionally, a higher tendency towards obesity has been reported to be associated with abdominal pain and diarrhea.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16234045&dopt=Abstract .

Thus, the answer to the question below, whether too much fat increases CRP or if high levels of CRP make people fat, may be that both obesity and elevated CRP levels are related to diarrhea associated  functional bowel disorders like IBS.  Addressing the causes of the bowel disorder may reduce CRP levels, normalize leptin function and reduce obesity.  Future research should be done to investigate this possibility.

John W. Cartmell, MS
www.dietadvisor.com


What Causes Obesity?
WASHINGTON DC (myDNA News) http://www.mydna.com/health/weight/news/news_20060414_obesity_causes.html
Apr 13, 2006

As the rate of overweight Americans continue to rise, research now suggests that obesity is due at least in part to an attraction between leptin, the hormone that signals the brain when to stop eating, and a protein called C-reactive (CRP).

University of Pittsburgh researchers report in the journal Nature Medicine that when CRP binds to leptin, its hold impairs the hormone's ability to control appetite.

"There's been a lot of interest in leptin as a means to curb appetite and reduce weight, but clinical trials have had disappointing results," said study author Allan Z. Zhao, Ph.D., assistant professor of cell biology and physiology at the University of Pittsburgh School of Medicine, in a written statement.

Zhao said his study suggests researchers should focus their attention on an approach that disrupts the interaction between leptin and CRP, which would allow the hormone to resume its regulatory role.

"We need to better understand how this interaction works and investigate the underlying mechanisms involved," he said.

The amount of fat regulates the amount of leptin produced by the body: the more fat, the more of the hormone. Obese people produce higher levels of leptin, but somehow they're resistant to its effects. This has led researchers to focus on the interaction between CRP and leptin, which is actually Greek for the word "thin."

Zhao said that the binding of CRP, which is also elevated in obese people, to leptin might help explain why the hormone is not effective.

CRP is produced by the liver and typically rises as part of the immune system's inflammatory response. Medical experts are beginning to use it as a marker for hypertension and heart disease both complications of obesity.
"We know that CRP binds to leptin, and this impairs its signaling," Zhao explained. "But we don't know how this is so. It may be that the coupling of the two makes crossing the blood-brain barrier difficult, or it may be that as a package, it can't bind to leptin receptors in the brain."

Still, an unanswered question for Zhao and his team is whether too much fat increases CRP or if the high levels of CRP makes people fat.

"There is some research showing once the body gains enough body fat to become obese, the body fat becomes the largest endocrine gland in the body and begins to send messages to secrete pro-inflammatory chemicals," said Lori Elyz Winterstein, M.A., R.D., lead dietician and lifestyle counselor at the Scripps Center for Integrative Medicine in La Jolla, Calif. "This creates a negative loop in various ways. The resulting inflammatory cascade, such as cortisol and now the possibility of CRP makes losing the weight more difficult biologically.

"The good news is good nutrient-dense nutrition can also help reduce inflammation and assist with the weight-loss process," Winterstein said


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