More press reports on this story.
Note that the reports below talk merely of "overnutrition" and a "high fat diet" whereas in Demi's post above it says "a In mice, a protein connected to inflammatory reactions appeared to be switched on when the animals were given a high fat, high sugar diet."
Strange the things the press misreports.
I am disappointed that it seems the distinct roles of high-fat and high carb have not been explored separately, but that one hopes that will be done soon.
In the interim it looks like the press releases, especially in the mass-market press, are interpreting this as an "anti fat" rather than anti high carb/insulin result.
If anyone can get into the full text on the actual feed ratios I am all ears.
" ***** Medical News: General Neurology
http://www.medpagetoday.com/Neurolo...rology/tb/11155
Brain Inflammation Pathway Linked to Murine Obesity
By Michael Smith, North American Correspondent, MedPage Today
Published: October 02, 2008
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine. Earn CME/CE credit
for reading medical news
MADISON, Wis., Oct. 2 -- Blocking an inflammatory pathway in the hypothalamus can prevent obesity, at least in mice, researchers here said.
Action Points
* Explain to interested patients that the role of inflammation in diseases of over-nutrition -- such as type 2 diabetes -- is not completely understood.
* Note that this study, in experimental mice, suggests that an inflammatory pathway in the brain plays a key role and might open new therapeutic options.
The pathway involves a mediator of metabolic inflammation -- dubbed IKKß/NF-kB -- that is normally inactive in the hypothalamus, even though it is enriched in hypothalamic neurons, according to Dongsheng Cai, M.D., Ph.D., of the University of Wisconsin, and colleagues.
A series of animal and in vitro experiments showed that IKKß/NF-kB can be activated by either an acute or chronic oversupply of nutrients, Dr. Cai and colleagues reported in the Oct. 3 issue of Cell.
The "discoveries offer potential for treating these serious diseases" caused by overnutrition, such as type 2 diabetes, the researchers said.
Moreover, because IKKß/NF-kB is normally inactive in the central nervous system, suppressing it in the hypothalamus "is likely a safe approach," they argued.
When IKKß/NF-kB is activated, they said, insulin and leptin signaling in the mediobasal hypothalamus is disrupted, leading to energy imbalance and eventually obesity.
In mice, preventing such activation -- either genetically or through viral gene therapy -- restored energy balance and prevented obesity even when animals were fed a high-fat diet, Dr. Cai and colleagues said.
It was already known, Dr. Cai and colleagues said, that overnutrition can spark inflammatory responses in peripheral metabolic tissues, including the muscles and liver.
But it wasn't known what effect metabolic inflammation had in the central nervous system.
To help fill the gap, the researchers undertook a series of experiments, starting with a look at the effects of a high-fat diet in normal mice and a normal diet in mice predisposed to obesity.
In both cases, they found IKKß/NF-kB activity increased -- two-fold in the normal mice and up to six-fold in the genetically modified animals.
The increased activity of the IKKß/NF-kB pathway, though, is not a function of obesity itself, they found. Non-obese mice that were fasted overnight followed by a six-hour infusion of 20% glucose into the third ventricle of the hypothalamus showed a significant increase in IKKß/NF-kB activity (P<0.05) compared with control animals.
On the other hand, a normal physiological supply of nutrients -- re-feeding after fasting, for example -- did not trigger the increased activity.
In another experiment, mice on a high-fat diet were injected with a viral vector that either increased or decreased the activity of IKKß. The researchers found significant changes -- either up or down -- in food intake and weight gain (P<0.05), compared with control animals.
The mechanism may involve endoplasmic reticulum stress, which has been associated in other tissues with diseases of overnutrition, the researchers said.
They found that activation of IKKß/NF-kB by a high-fat diet is associated with such stress, but that acute use of an inhibitor of endoplasmic reticulum stress suppressed activation of IKKß/NF-kB.
On the other hand, in animals fed a normal diet, an inducer of endoplasmic reticulum stress increased activation of IKKß/NF-kB, they found.
Another series of experiments showed that activation of IKKß/NF-kB interrupts normal signaling by insulin and leptin in the hypothalamus.
Because of that finding, the researchers hypothesized that blocking the activity of IKKß/NF-kB in neurons critical for insulin and leptin signaling would have beneficial metabolic effects in animals fed a high-fat diet.
To test the idea, they bred mice in which only the AGRP neurons -- a critical source of hypothalamic insulin and leptin signaling -- had the IKKß/NF-kB pathway blocked.
The animals were essentially normal in growth, offspring frequency, and activity, the researchers said, and when they were fed a normal diet they gained weight at about the same rate as controls.
On the other hand, when they were fed a high-fat diet, they ate less and gained less weight than controls. After 12 weeks, their body weight on average was 13.1% less than that of the controls and they ate 10.2% less -- differences that were significant at P<0.05 and P<0.01, respectively.
"Altogether, our results suggest a novel therapeutic strategy for combating the ever-increasing spread of obesity and associated diseases," the researchers summed up.
The study was supported by the NIH, the American Diabetes Association, and the University of Wisconsin-Madison. The researchers reported no conflicts.
Primary source: Cell
Source reference:
Zhang, et al "Hypothalamic IKKß/NF-kB and ER Stress Link Overnutrition to Energy Imbalance and Obesity" Cell 2008; 135: 61-73.
Additional General Neurology Coverage "
*****"
Primary source link above is as below. Seems to be just an abstract.
*****"
Summary
Overnutrition is associated with chronic inflammation in metabolic tissues. Whether metabolic inflammation compromises the neural regulatory systems and therefore promotes overnutrition-associated diseases remains unexplored. Here we show that a mediator of metabolic inflammation, IKKβ/NF-κB, normally remains inactive although enriched in hypothalamic neurons. Overnutrition atypically activates hypothalamic IKKβ/NF-κB at least in part through elevated endoplasmic reticulum stress in the hypothalamus. While forced activation of hypothalamic IKKβ/NF-κB interrupts central insulin/leptin signaling and actions, site- or cell-specific suppression of IKKβ either broadly across the brain or locally within the mediobasal hypothalamus, or specifically in hypothalamic AGRP neurons significantly protects against obesity and glucose intolerance. The molecular mechanisms involved include regulation by IKKβ/NF-κB of SOCS3, a core inhibitor of insulin and leptin signaling. Our results show that the hypothalamic IKKβ/NF-κB program is a general neural mechanism for energy imbalance underlying obesity and suggest that suppressing hypothalamic IKKβ/NF-κB may represent a strategy to combat obesity and related diseases.
******"
New twist in brain obesity riddle
Linear Mode
