Nip/Tuck/NPY Injections

"Tell me what you don't like about yourself."

Scientists discover key to manipulating fat

Washington, D.C. − In what they call a "stunning research advance," investigators at Georgetown University Medical Center have been able to use simple, non-toxic chemical injections to add and remove fat in targeted areas on the bodies of laboratory animals. They say the discovery, published online in Nature Medicine on July 1, could revolutionize human cosmetic and reconstructive plastic surgery and treatment of diseases associated with human obesity.

"Make me beautiful"

In the paper, the Georgetown researchers describe a mechanism they found by which stress activates weight gain in mice, and they say this pathway -- which they were able to manipulate − may explain why people who are chronically stressed gain more weight than they should based on the calories they consume.

This pathway involves two players -- a neurotransmitter (neuropeptide Y, or NPY) and the receptor (neuropeptide Y2 receptor, or Y2R) it activates in two types of cells in the fat tissue: endothelial cells lining blood vessels and fat cells themselves. In order to add fat selectively to the mice they tested, researchers injected NPY into a specific area. The researchers found that both NPY and Y2R are activated during stress, leading to apple-shape obesity and metabolic syndrome. Both the weight gain and metabolic syndrome, however, were prevented by administration of Y2R blocker into the abdominal fat.

Neuropeptide Y (NPY) is a neurotransmitter in the brain and in the periphery (including the sympathetic nervous system). In the latter locale, NPY is released from sympathetic neurons in abdominal fat during times of chronic stress, which can lead to abdominal obesity (Kuo et al., 2007; Warne & Dallman, 2007). NPY also appears to be involved in an unbelievable array of processes (including effects on vascular smooth muscle cells and endocardial endothelial cells, the immune system, estrogen-induced synapse formation in the hippocampus, bone remodeling, vascular remodeling, and energy homeostasis), and is viewed as a potential drug development target for neuroblastomas and other cancers, alcohol abuse, major depression, pain, and gene therapy in epilepsy, as well as obesity [why not examine the entire Feb 2007 issue of Peptides, NPY AND COHORTS IN HUMAN DISEASE, which has papers from the Proceedings of the 8th International NPY meeting]. These actions are mediated by at least four different NPY receptor subtypes (Y1, Y2, Y4, Y5).

"Perfect soul"

"We couldn’t believe such fat remodeling was possible, but the numerous different experiments conducted over four years demonstrated that it is, at least in mice; recent pilot data also suggest that a similar mechanism exist in monkeys as well," said the study's senior author, Zofia Zukowska, M.D., Ph.D., professor and chair of the Department of Physiology & Biophysics at Georgetown University Medical Center.

"We are hopeful that these findings might eventually lead to control of metabolic syndrome, which is a huge health issue for many Americans," she said. "Decreasing fat in the abdomen of the mice we studied reduced the fat in their liver and skeletal muscles, and also helped to control insulin resistance, glucose intolerance, blood pressure and inflammation. Blocking Y2R might work the same way in humans, but much study will be needed to prove that."

"Perfect mind"

Fig. 1 (Warne & Dallman, 2007) - A new role for neuropeptide Y.
Kuo et al. focus on the direct effects of neuropeptide (NPY) on adipocyte physiology in repeatedly stressed animals fed a palatable high-fat diet. NPY acts on preadipocytes, endothelial cells and macrophages to promote adipocyte proliferation and maturation as well as to induce new capillaries to supply nutrients to the increased fat mass. NPY is secreted from sympathetic nerve terminals in response to stressors. The blockade of either NPY receptors or glucocorticoid receptors blocks the abdominal obesity that occurs with stressors and a high-fat diet. [Katie Ris]

"Perfect face" [warning: gory]

And perhaps the most rapid clinical application of these results will be in both cosmetic [see Nip/Tuck] and reconstructive plastic surgery, said co-author Stephen Baker, M.D., D.D.S, associate professor of plastic surgery at Georgetown University Hospital. The ability to add fat as a graft would be useful for facial rejuvenation, breast surgery, buttock and lip enhancement, and facial reconstruction, he said, and using injections like those tested in this study could make fat grafts predictable, inexpensive, biocompatible and permanent.

Equally important, blocking Y2R resulted in local elimination of adipose, or fat, tissue, said Baker. "This is the first well-described mechanism found that can effectively eliminate fat without using surgery,” he said. “A safe, effective, non-surgical means to eliminate undesirable body fat would be of great benefit to our patients."

"A perfect lie"



References

Kuo LE, Kitlinska JB, Tilan JU, Li L, Baker SB, Johnson MD, Lee EW, Burnett MS, Fricke ST, Kvetnansky R, Herzog H, Zukowska Z. (2007). Neuropeptide Y acts directly in the periphery on fat tissue and mediates stress-induced obesity and metabolic syndrome. Nat Med. 13:803-11.

The relationship between stress and obesity remains elusive. In response to stress, some people lose weight, whereas others gain. Here we report that stress exaggerates diet-induced obesity through a peripheral mechanism in the abdominal white adipose tissue that is mediated by neuropeptide Y (NPY). Stressors such as exposure to cold or aggression lead to the release of NPY from sympathetic nerves, which in turn upregulates NPY and its Y2 receptors (NPY2R) in a glucocorticoid-dependent manner in the abdominal fat. This positive feedback response by NPY leads to the growth of abdominal fat. Release of NPY and activation of NPY2R stimulates fat angiogenesis, macrophage infiltration, and the proliferation and differentiation of new adipocytes, resulting in abdominal obesity and a metabolic syndrome-like condition. NPY, like stress, stimulates mouse and human fat growth, whereas pharmacological inhibition or fat-targeted knockdown of NPY2R is anti-angiogenic and anti-adipogenic, while reducing abdominal obesity and metabolic abnormalities. Thus, manipulations of NPY2R activity within fat tissue offer new ways to remodel fat and treat obesity and metabolic syndrome.

Warne JP, Dallman MF. (2007). Stress, diet and abdominal obesity: Y? Nat Med. 13(7):781-3.


A Perfect Lie (Gabriel & Dresden Remix) by The Engine Room

Make me beautiful
Make me beautiful

Perfect soul
Perfect mind
Perfect face
A perfect lie

Make me beautiful
Make me beautiful

Perfect soul
Perfect mind
Perfect face
A perfect, perfect soul
Perfect mind
Perfect face

A perfect lie
A perfect lie

A perfect lie
A perfect lie

I'm Number 63,645! Whee!!

Since other people¹ have been touting their Technorati ratings lately, I wanted to participate in the fun. And it looks like The Neurocritic ranks an impressive 63,645^th.

[anyway, it seemed liked the thing to do at 0707 on 07/07/07...]


Footnote

¹two neurobloggers

Echo
. . .
I crave an empty lifestyle
I crave the very loudest sound
I'm chasing everybody
I'm shaking everybody down
Do you hear the loudest sound?
And you and me in the echo?

-- Kristin Hersh

Lesionnaire's Syndrome

The Neurocritic would also like to thank Dr. Walterfang for drawing our attention to a terrible new disease afflicting quantitative neuroimaging laboratories around the globe. The sweatshop conditions contributing to this pandemic must end!

"Lesionnaire's syndrome"
Dennis Velakoulis, Christos Pantelis and Mark Walterfang
MJA 2005; 183 (11/12): 679.

The explosion in psychiatric neuroimaging research has led to the establishment of stressful and dark neuroimaging laboratories in which young researchers sweat in front of computer monitors performing laborious and tedious imaging analysis. These conditions have contributed to the development of a new psychiatric syndrome, described below.

Read the Diagnostic criteria to see if you, too, might be affected. As a cautionary tale, read the Case report of a 38-year-old psychiatrist who spent hundreds of hours tracing hippocampal volumes on MRI scans.

MORE on Neurobiological Correlates of Melbourne-Sydney Rivalry

Figure 2 (Velakoulis et al., 2007): Anterior cingulate region showing inter-state differences in cortical thickness, overlaid on a geographic map of Australia. The region-of-interest corresponded to the portion of the anterior cingulate gyrus anterior to the black line, and was delineated on the reconstructed cortical surface, as shown.

The Neurocritic covered the dueling Australian cinguli back in May. The experiment revealed that Melbourne residents have a substantially thicker anterior cingulate cortex (ACC) than Sydney residents, and this difference remained highly significant when controlling for age and intracranial volume. One of the study's authors, Dr. Mark Walterfang, commented on that post, and has made the uncorrected proof available in a blog exclusive.

The hypotheses were as follows:

-- Australian Football League (AFL) premierships won by each city would be associated with greater cortical thickness due to the endorphin-mediated release of neurotrophins, and a relative lack of cortisol-related neuronal loss.

-- Median 2005 property prices would be associated with reduced cortical thickness due to the atrophic effects of high levels of circulating cortisol in stressed mortgagees.

-- Cortical thickness would be greatest in the city with the higher intellectual capital as measured by the number of 2005 NHMRC grants.

The results indicated that Sydney residents did come up with the short end of the stick for all measures:

...the other variables compared to ACC thickness measures suggested that Sydney-siders were subject to higher property prices, a lower number of successful NHMRC grant applications, and significantly less success with respect to the number of AFL premierships won.

Clearly, this is a landmark study that inaugurates the nascent field of Sociocompetitive Neuroscience (aka the Neurobiology of Civic Rivalry).

Reference

Velakoulis D, Fornito A, Walterfang M, Malhi G, Yucel M, Pantelis C. (2007). A tale of two cities: a neuroimaging investigation of Melbourne-Sydney rivalry comparing cortical thickness in healthy adults. Australas Psychiatry 15(1):67-71.

People Are Better Teachers Than Teletubbies

In this bit of startling news,

Toddlers learn their first words better from people than from Teletubbies.

But the initial comparison (discussed in the press release) wasn't between live Teletubbies and live people, or between televised Teletubbies and televised people, but between televised Teletubbies and live people.

Turn Off TV To Teach Toddlers New Words

. . .

Children younger than 22 months may be entertained, but they do not learn words from the television program, said Marina Krcmar, associate professor of communication at Wake Forest and author of the study.

"With the tremendous success of programs such as 'Teletubbies' that target very young children, it has become important to understand what very young children are taking away from these programs," Krcmar said. "We would like to think it could work, that Teletubbies and other programs can teach initial language skills. That is not true."

In the study, Krcmar evaluated the ability of children ages 15 -- 24 months to learn new words when the words were presented as part of a "Teletubbies" program. She then evaluated their ability to learn the new words from an adult speaker in the same room with them.

However, it was good to see mention of the appropriate comparison at the end of the press release:

As part of the study, Krcmar also found that the children were just as attentive to an adult speaker on the small screen as they were to the Teletubbies characters. And, the children identified the target words more successfully in response to a video of an adult speaker than to the Teletubbies.

The results appeared in the journal Media Psychology. I don't have online access to the article, but one question is whether the researchers considered Teletubby Talk:

Eh-oh!

Again-Again!

Big hug

It appears not. And what do the show's creators say about language acquisition?

The show's co-creator Andy Davenport studied speech sciences before embarking on a career in children's TV. So the development of Teletubby talk came about through a combination of his experience and observing children closely.

"We thought long and hard about the way the Teletubbies should speak," says Andy. "After a lot of thought we came up with a play language based on the early speech of a young child. To small children, Teletubby words carry as much meaning as normal words."

Reference

Marina Krcmar, Bernard Grela, Kirsten Lin. (2007). Can Toddlers Learn Vocabulary from Television? An Experimental Approach. Media Psychology, Vol. 10, No. 1: pages 41-63.

This study was inspired by the rise in television targeting toddlers and preverbal infants (e.g., Teletubbies, Baby Mozart). Overall, we investigated if very young children who are in the early stages of language acquisition can learn vocabulary quickly (fast map) from television programs. Using a fast mapping paradigm, this study examined a group (n = 48) of toddlers (15—24 months) and their ability to learn novel words. Utilizing a repeated measures design, we compared children's ability to learn various novel words in 5 different conditions. These included the presentation and identification of a novel word by an adult speaker via live presentation when the toddler was attending (i.e., joint reference), an adult via live presentation when the toddler was not attending, an adult speaker on television, and an edited clip from a children's television program (Teletubbies). Overall, the toddlers were most successful in learning novel words in the joint reference condition. They were significantly less successful in the children's program condition. Furthermore, there was a significant interaction between age and condition on children's performance. Both younger (15—21 months) and older (22—24 months) participants identified the target objects when they were taught the novel word by an adult speaker; however, it appeared that children under the age of 22 months did not identify the target item when they were taught the novel word via the television program.

Neurosurgeon/Terrorist?

Via The Null Device:

Al-Qaeda's best and brightest

Apparently, one of the suspects in the recent UK terrorist attacks was a neurosurgeon. I guess this shows that suicide bombing isn't brain surgery.

Also of note:

A Surgeon’s Trajectory Takes an Unlikely Swerve

. . .

He [Simon Plant, landlord] said that the Ashas were model tenants, but that Dr. Asha, a Palestinian with Jordanian citizenship, had something of a condescending manner. "He got a slight attitude," said Mr. Plant, an elevator engineer. "He had a sense of self-importance about being a doctor. You could definitely feel it."

. . .

Dr. Asha, 26, whose specialty is neurosurgery, recently started work at the North Staffordshire Hospital in Stoke-on-Trent. According to the General Medical Council in Britain, Mohammed Jamil Abdelqader Asha completed his medical studies in Jordan in 2004. His limited registration allowed him to work for the National Health Service under supervision. Until last July, he worked as a doctor at Royal Shrewsbury Hospital and the Princess Royal Hospital, both in Telford.

A 26 year old neurosurgeon? OR was he a mere neurologist?

A photo of suspect Mohammed Asha, shaking hands with Jordan's Queen Noor

Faces ARE Really Special, After All

OR: Bentin, Taylor, Rousselet, Itier, Caldara, Schyns, Jacques, & Rossion respond to Thierry et al.


from Bentin et al. (2007): Supplementary Figure 4. B. These histograms derived from Thierry et al.'s (2007) data provides the best illustration that ISPV cannot account for N170 amplitude, showing an inverse relationship between within-category picture similarity (highest for faces) and N170 amplitude (highest for cars) in the low ISPV condition and similar N170 amplitudes for faces and cars in the high ISPV condition despite lower picture similarity for faces than cars (Experiment 1).

The Phineas Gage Fan Club has noted the publication of a letter to the editor in Nature Neuroscience that's critical of the ISPV paper published by Thierry et al. (2007a) in April. What's ISPV? That's interstimulus perceptual variance, and it was a factor purportedly uncontrolled in prior studies of the N170, an electrophysiological signal thought to be selective for faces (see Are Faces Special?). The specificity of the N170 for faces (vs. other objects) is part of a larger debate on whether faces have a privileged processing status or not (the latter view being that faces are just one example of a stimulus class that requires substantial expertise in order to distinguish between similar exemplars). Then the recent NN paper added more fuel to the fire.

Briefly, in their original article, Thierry et al. argued that previous studies of the N170 component did not adequately control for variability across stimulus classes, i.e., face stimuli were much more similar to each other than the non-face stimuli. When ISPV was more tightly controlled, the selectivity of N170 for faces (vs. cars) went away.

Then, Bruno Rossion, from the Face Categorisation Lab in Belgium, commented that these experiments were kind of... bad and (ironically) failed to adequately control for interstimulus variance, among other things (see also C'mon, Aren't Faces REALLY Special?). The correspondence from Bentin, Rossion, and six more authors (along with a reply by Thierry et al.) appears in the July issue of NN. Johan has done a nice job summarizing the debate in N170 face controversy continues, so I'll only add a few choice quotes:

Here we [Bentin et al.] demonstrate that ISPV was actually controlled in many studies, yet the N170 effect remained conspicuous (Fig. 1 and Supplementary Figures 1,2,3 online). Evidently, Thierry and colleagues' claim is wrong and misleading.

Continuing merrily along:

In addition to their factual error, they failed to note the striking contradiction between their hypothesis and the existing literature. Most notable are the larger N170 for inverted than for upright faces, the larger N170 for upright than for inverted Mooney faces..., [etc.] All these modulations of N170 are robust despite identical stimuli in different conditions, hence identical ISPV.

My favorite, however, is the title for Supplementary Figure 4: "Self-contradictions in Thierry et al.":

Supplementary Figure 4. A. While Thierry et al. claimed to have controlled for inter-stimulus similarity between pictures of faces and objects (exact values not reported), their own data suggest otherwise.

And the debate continues...

References

Bentin S, Taylor MJ, Rousselet GA, Itier RJ, Caldara R, Schyns P, Jacques C, Rossion B. (2007). Controlling interstimulus perceptual variance does not abolish N170 face sensitivity. Nature Neurosci. 10:801-802.

[apparently, the original title for this submission was "Much ado about nothing: controlling interstimulus perceptual variance does not abolish N170 face sensitivity," as listed in the publications of the Face Categorisation Lab. I would imagine the editors at NN did not take too kindly to the "much ado" part...]

Thierry G, Martin CD, Downing P, Pegna AJ. (2007a). Controlling for interstimulus perceptual variance abolishes N170 face selectivity. Nature Neurosci. 10:505-511.

Thierry G, Martin CD, Downing P, Pegna AJ. (2007b). Is the N170 sensitive to the human face or to several intertwined perceptual and conceptual factors? Nature Neurosci. 10:802-803.