Reperfusion Injury and Luteolin

I found the basic science article about Leukocyte accumulation in reperfusion injury after stroke to be pretty interesting so I went and found another article that has to do with reperfusion injury. The paper I read was title “Postischemic administration of liposome-encapsulated luteolin prevents against ischemia-reperfusion injury in a rat middle cerebral artery occlusion (MACO) model” (long title I know). Luteolin is a flavonoid (also collectively known as Vitamin P and citrin)that from preliminary research is thought to have a role as an antioxidant, a free radical scavenger, or an immune system modulator. In basic research results show it could also work as an anti-inflammatory agent.

This study was done by taking a group of female rats and dividing them it to four different groups. These groups were: sham group with liposome solvent, model group with liposome solvent, treatment group with 5mg/kg lipLU, and treatment group with 20mg/kg lipLU (lipLU = liposome-encapsulated luteolin). They performed a MACO on all groups except for the sham group, the filament was removed 40 minutes after induction of ischemia. Some of the rats were killed in order to look at brain slices.

What they found was that when multiple administration of lipLU beginning at 6 hour post reperfusion showed a decrease in the symptom score and pronounced enhancement of balance score on day 7 (in comparison to those rats without lipLU) and there were even more behavioral improvements by day 14. This showed that the lipLU possessed a long lasting anti ischemic activity, they confirmed this by looking at brain slices that showed delayed action in improvement of the histological injury after treatment. The study also showed that with the ischemic attach and reperfusion (I/R) there was an increase of reactive oxygen species (ROS) and a inhibition of endogenous antioxidant defense system (CAT and GSH) showing an imbalance between the species. With those treated with lipLU conferred reversing actions on the increase in ROS production and on the decrease of endogenous antioxidant GSH and CAT activity. The researchers say that this is what is improving the brain damage by rebalancing the pro-oxidant/antioxidant force.

This study shows that luteolin acts by neroprotection in primary cultured neurons exposed to oxidative stress and anti-ischemia in animals insulted by I/R (Zhao 7). I think that this study is a good start and that this luteolin should be studied more in the future so that the exact mechanisms can be found and to see how it would translate to human models.

References:

Zhao, Gang, Shao-Yun Zang etal. "Postischemic Administration of Liposome-
encapsulated Luteolin Prevents Aganist Ischemia-reperfusion Injury in a Rat
Middle Cerebral Artery Occlusion Model." Journal of Nutritional Biochemistry
(2010): 1-8. Print.

Progesterone and Ischaemia

After reading the NO, ischaemia and brain inflammation article from last Monday's discussion, I was interested in the effects of progesterone following ischaemia. The article talked about how progesterone can decrease lesion volume and enhance the functionality of both male and female rodent subjects. Estrogen is thought to be neuroprotective because it blocks NOS-2 expression.

I found an interesting article from the American Heart Association, which studied the effects of progesterone on ovariectomized rats. These rats were given hormone treatments before MCAO. The study showed that the progesterone treatment did not improve brain injury in the ovariectomized rats. It also showed that chronic progesterone levels worsened the lesion volume.
It seems as though progesterone is neuroprotective in males and pre-menopausal women. It is known that pre-menopausal women have a much lower risk for stoke than men. But stroke risk in post-menopausal women increases greatly.

In the study of ovariectomized rats, it is suggested that lower levels of progesterone may be beneficial, and that progesterone exposure duration may also play an important role. Progesterone withdrawal could also have some effect on the rats. Rats going through progesterone withdrawal were more prone to seizure-activity. The article makes an important point about the interaction of progesterone and estrogen; progesterone is not needed for estrogen to reduce stroke injury, but estrogen needs to be primed for progesterone to be effective. Combination these hormones could produce beneficial effects. Estrogen is thought to be neuroprotective even in ovariectomized rats.

This study did not talk about nitric oxide (NO) at all, but it's possible that NO plays no role in progesterone's effect on ischaemia. I would guess that it does play a role though, because NOS-2 expression can be blocked by estrogen, and estrogen and progesterone are similar hormones. I think that when combined with estrogen, progesterone could also block NOS-2 expression, which would decrease lesion volume in ovariectomized rats.

References:
Murphy, S., C.L. Gibson. "Nitric oxide, ischaemia and brain inflammation."
Biochemical Society Transactions 35.5 (2007): 1133-1137. Web. 20 Feb 2011.

Murphy, Stephanie J., VMD, PhD, Richard J. Traystman, PhD, Patricia D. Hurn, PhD. "Progesterone Exacerbates Striatal Stroke Injury in Progesterone-Deficient Female Animals."
Stroke 31 (2000): 1173-1178. Web 27 Feb 2011.
http://stroke.ahajournals.org/cgi/content/full/strokeaha;31/5/1173.

Gibson, Claire L., Laura J. Gray, Philip M. W. Bath, and Sean P. Murphy. "Progesterone for the treatment of experimental brain injury; a systematic review."
Brain A Journal of Neurology 131.2 (2007): 318-328. Web. 27 Feb 2011.
http://brain.oxfordjournals.org/content/131/2/318.full

Sodium and NO production figure

Here is the figure.... Sorry it didn't upload!

Cellular Adhesion and a little Acute Inflammation

Hey everyone!
I'm a huge fan of visual learning devices, and I find this video particularly helpful. The inflammation part is slight, but if you ever wondered "what the heck are they talking about?" in any kind of cellular/molecular biology class, this is a great tool to clarify some points. They rope you in the beginning showing leukocyte adhesion to the endothelial cell, then they stray away from the point for a few minutes but discuss some interesting concepts regarding the cell. And finally, at the end, they return to the inflammation discussion. They show I-CAM and its role in cell adhesion as well as the extravasation of the leukocyte below the endothelial layer, which is how atherosclerotic plaques are formed. Between this and lots of other diagrams that we've seen, I think we can get a pretty full picture of what's happening. Thanks, Harvard!

http://multimedia.mcb.harvard.edu/anim_innerlife.html

Also, in response to my own question from Monday regarding why I-CAM isn't upregulated in response to inflammatory stimuli: turns out that I-CAM1 is constitutively expressed and is not upregulated, whereas I-CAM2 is upregulated and has a huge role in stroke etiology. Those tricksters!

Sodium and NO production

Hello All,

A nutrition list-serv that I am a member of posted a link to an article that I found very interesting and thought it went along with a few of our discussions on Monday. The link for the article is below.

http://www.stonehearthnewsletters.com/diet-soda-may-raise-odds-of-vascular-events-salt-linked-to-stroke-risk/nutrition/

The title is one that grabs the reader: diet soda may raise the odds of vascular events; salt linked to stroke risk. It reminded me of the thought we had in class regarding the media. Lay articles that use a little bit of truth to focus on in order to increase fear/interest in the article or website. At the end of this brief article, you realize it's not the diet soda in the diet that caused increased risk of cerebral vascular events but sodium content of the entire diet.

We are all aware of the affects sodium intake has on stimulating the renin-angiotensin system, thus increasing sodium reabsorption, leading to increased intervascular volume and resulting in hypertension. I started to wonder sodium's influence on the inflammatory system. This brought me to a a review article: Salt Intake, Endothelial Cell Signaling and Progression of Kidney Disease. It discusses the impact salt intake can have on endothelial signaling, specifically the effects on NO. Increased salt intake led to impairment of the negative feedback system leading to over expression of NOS eventually leading to organ damage.

Here is the brief diagram they proposed: increased blood flow leads to expression of p38 and MAPK, increasing TGF-beta 1 and thus increasing NO expression.

It seems that sodium has a direct effect on hypertension, but there are many pathways that we have yet to discover, regarding inflammation and CVAs.

Sanders, P. Salt Intake, Endothelial Cell Signaling and Progression of Kidney Disease. Hypertension. 2004;43:142-146.

Periodontitis and Cerebrovascular Disease

After reading the lay article about how gum disease was linked to stroke and seeing the study they used I figured that I should reaad said study. This study was a pretty big one, at the beginning they had around 2,280 men that were interested in taking part in the study. When choosing people to be part of the study they looked at things like: levels of education, income, marital status, BMI, smoking, and quite a few more variables. Eventually the group was decreased to 1,137 males. There were two ways that they examined the teeth and how they compared to cerebrovascular disease these were: periodontal bone loss and cumulative probing depth. They study showed a positive association between periodontal bone loass and the incident of cerebrovascular disease. This association however was independent of cardivascular risk factors. They also found that there was a higher association with men that were younger than 65 years old. There was found to be no association with cumulative probing depth and incident of cerebrovascular disease. They believe that the casual (direct or indirect effect of infection and inflammatory response) and the non casual (chronic periodontitis) could be the cause of this association.

In terms of inflammation and how it relates to the study we could think of it as Dr. Cohen said in class. That the periodontal bone loss (periodontitis) could be looked at as being a response to chronic inflammation. While the probing depth is a result of acute inflammation.

I think that this study could be used as a starting point in a sense to fuel future studies that maybe focus on just the periodontal bone loss (periodontitis) and what factors of this could lead to cerebrovascular disease, in both men and women.

References:

Dietrich, Thomas, Elizabeth A. Krall, etal. "Periodontitis and Incidence of Cerebrovascular Disease in Men." Annals of Neurology 66.4 (2009): 505-12.

Wobenzym Wobenzym Wobenzym

I just thought of what I wanted to say in class about the Wobenzym articles being in German. It was a general comment, but I guess my mind went blank or something. Anyway, even if you wanted to know more about these enzymes, and you knew that the best way to find legitimate information was through primary scientific articles, you would not be able to read the articles that you found since they are in German (and other languages, I think). Even if you knew German as a second language, I don't think you would want to struggle through a research paper in a foreign language. Right?I am sure Gordon thought this through too.

Slowing the Growth of Childhood Obesity

Childhood obesity is a serious problem in the world today and is growing at an alarming rate. The national prevalence of overweight and obesity in children 8-12 has almost quadrupled in the last 25 years making up the 30% of children who are obese. Not a lot of research has been conducted on younger children ages 2 and up which leaves a huge gap in the literature and hurts the population in terms of having preventative guidelines to follow in raising children to be healthy non obese individuals. This lack of research and preventative care could play a part the current prevalence of obesity in adults nearly 60% now and with the addition of growing childhood obesity could reach critical levels. Even though there isn't an abundance of research to guide practitioners there are some basic ideas that show results in lowering the BMI and risk of developing obesity or other obese related diseases.

First, and of undeniable importance, is education in nutrition and exercise. It has been shown that a cognitive-behavioral aspect is beneficial while participating in the intervention. Also limited sedentary activities like video games and positive reinforcement for physical activities and good food choices. As far as improvements clinically, BMI for children showing signs of obesity from early on, ages 2 and up for every visit. As well as an evaluation based on historical (obese parents), and physical information placing a child at risk for development of obesity or other related disease.

It's surprising that this seems so simple and yet not a lot of research has gone into these issues. Only 2 studies were found in the U.S both of which validity is an issue. The U.S has among the highest obesity levels in the world so why are we seemingly not doing anything about it? At any rate something needs to be done now, and preventative medicine needs to become mainstream or more understood so that we have a chance at stopping this terrifying trend.

NO and Estrogen

In the NO, ischaemia, and brain inflammation article, the authors mention that the volume of infarction was found to be smaller in female mice after ischemic stroke compared to male mice, which was found to be due to estrogen regulation of NOS-2 expression. I was intrigued by the fact that these two compounds are interactive. It may have been obvious to some people, but it was not to me. So I looked it up. And I found lots of interesting articles, some of which I listed at the bottom of this post. It is fascinating to make connections between seemingly distant processes, but I that is the beauty of physiology (and pathophysiology), and especially immunology. In the diagram (has link to a website) you can see so many different players: NOS, estrogen, OPG (soluble RANKL) are all involved in osteoclastogenesis as well. So in reality, osteoporosis, cardiovascular disease, and stroke (and gum disease, too from that one article :), etc... are intricately related.

From the Karpuzoglu E paper, it seems that there are still come controversies and gaps in the literature about the influence of estrogen on NO.

In the more recent paper by White et. al, the authors hypothesize that the ratio between NO and superoxide (a ROS) is what is important. So basically maintaining a "concentration" of the beneficial NOS species, which can be regulated by estrogen apparently, (from the Murphy paper we read in class) is pertinent.

Steroids. 2010 Nov;75(11):788-93. Epub 2010 Jan 7.

Estrogen and oxidative stress: A novel mechanism that may increase the risk for cardiovascular disease in women.

White RE, Gerrity R, Barman SA, Han G.

Nitric Oxide. 2006 Nov;15(3):177-86. Epub 2006 May 2.

Estrogen regulation of nitric oxide and inducible nitric oxide synthase (iNOS) in immune cells: implications for immunity, autoimmune diseases, and apoptosis.

Karpuzoglu E, Ahmed SA.

Estrogen Modulation of Endothelial Nitric Oxide Synthase

Ken L. Chambliss and Philip W. Shaul

Vitamin C Lowers CRP Levels

I was curious after our discussion on curcumen and its proposed benefits and went on a search to see what other everyday supplements like vitamin C have been found to have beneficiary affects on inflammation. It turns out that vitamin c has been shown to lower crp levels in people who have above normal levels of crp in their blood (>1mg/L).

Why does this matter?

Elevated levels of crp is an indicator of inflammation and can be seen in an array of inflammation based pathologies such as liver failure, and heart disease. CRP binds phosphocholine expressed on dying or dead cells in order to start the signaling cascade ending in the termination of the dead cell. Using vitamin C to lower circulating CRP levels could aid in the treatment of inflammatory diseases and possibly slow down their progression.

So make sure you take your vitamins especially vitamin C!!

Eat to Live

"Eat to Live" by Joel Fuhrman, M.D. is diet book. Although I don't think that most people need to run out and try a new fad died, I wanted to share with you where I got exposure to this book. I'm taking a financing class at the University of Arizona and this is on the required book list. One of the important topics in my finance class is the cost of being overweight. There are far more costs then just the emotional toll it can take on a person. We have studied how it becomes a financial burden and is almost a gateway to other illnesses and disease. The book goes into how to eat for certain diseases and how to get a proper nutrient balance. It is one of the better diet books out there, but my point is not about the dieting but the money. If you can save money by eating groceries instead of fast food, you also save money by keeping your body healthy. Think of all the medications for high blood pressure, diabetes, and so on. If you don't get these illness associated with obesity then you save that money as well. So when people are out there saying the only reason they and their family don't eat well is the money, then someone should have them look at the long term and the actual savings involved with home cooked meals.

Another complain out of people is the time it takes to prepare meals. That seems to be just an excuse when we have such modern technology used for cooking. Is 30 minutes to back a chicken really too long? Its not like you can't do anything else in that 30 minutes. There are so many shows and books on how to cook healthy in less than 30 minutes. Another good option is tossing your meat into a crock pot. You can cook food for about 8 hrs while your not home and come home to a pot roast completely cooked . It takes a whole 5 minutes to put it in add some broth and chop some carrots to prepare. Really these excuses are not good enough to make up for the fact that you are hurting your body as well as your children's bodies.

A good article on this issue is:
Bussiness: Fast Food, Good and Hungry. ( January 01, 2010). The Economist, 395. 8687,65.

Inflammation and Metabolic Syndrome Lay Article

In the past I had read quite a few lay articles that will highlight basic sciences papers in their article in order to try support or promote a theory or a product. However, I have found that in actuality, these articles end up manipulating the basic science article and do not actually highlight a lot of truth. I found this article Inflammation: The relationship between metabolic syndrome, insulin resistance, and inflammation and thought that it would be interesting to examine as a class.



First, this is an incredibly short article, in fact it is so short that the content suffers a lot. The introduction is incredibly abrupt and neglects to introduce the topic well. The author does not define key terms very well and I believe that for a person who has little knowledge on this topic, they would be incredibly confused. The tone is often sarcastic and unprofessional with phrases such as "participants let medical folk poke, prod" being used.



Secondly, I don't believe that the topic of this article was ever intended on being addressed. Towards the end of the page under 'What this means to you' the first two sentences state the following, "Somehow the metabolic syndrome, insulin resistance, and inflammation are probably related. Figuring out how they're related is a whole different problem." I thought that that was supposed to be the topic of the article, and yet apparently it's a whole different problem. I don't believe that the author used the best facts from this basic science article to create an appropriate article. She just tried to summarize the abstract in as little words as possible to let the audience think that she knew something, when in fact it is apparent that she knows very little.



It is clear that the moral of the story is to "have less fat". She provides no dietary or exercise methods that may be helpful, she doesn't provide a very clear explanation as to what individuals should be concerned or who is at high risk. I feel as though this article could have been done well if the author did not decide to write it in 5 minutes. Do you think that this article provided individuals who are not well versed in this field with adequate information on the topic/basic science paper?



Check out the link here: http://health.usnews.com/usnews/health/briefs/diabetes_endocrine/hb041116b.htm

After two weeks of heavy reading about the subject, the link between inflammation and obesity/diabetes has never been so compelling. We’ve not only investigated recent evidence detailing this relationship, but we have also seen this field of research branch out into potentially therapeutic realms of science. All that we’ve seen, however, is actually science functioning inside of a very recently-established paradigm. Ever wonder what started this mushroom cloud of research on inflammation and metabolic disease?  Probably Hotamisligil et al.’s paper, “Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance.” This paper was published in 1993 (time reference: The Lion King came out in 1994!) and made the first molecular link between obesity and inflammation. Hotamisligil et al. found that TNF-α was overexpressed both locally and systemically in obese mice. Counteracting the inflammatory cytokine in turn increased insulin-stimulate d glucose uptake. This paper was groundbreaking! Check it out!

REFERENCES:

Hotamisligil , GS, NS Shargill and BM Spiegelman. "Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance." Science (1993) 259(5091): 87-91.

Ginseng and Diabetes

It is alarming how the supplement industry is not really strictly regulated by the FDA, especially when some of the doses of these supplements can be considered very high and can potentially induce pharmacologic effects (for example, multivitamins and minerals that provide way above and beyond the RDA). Perhaps, this is the case because a) there is scarcity of scientific evidence about some supplements, b) the properties of a compound of interest is complicated and c) there is more unknown than known about the bioactive compound/s in a supplement.

Nevertheless, there are some supplements, specifically those used in Traditional Chinese Medicine (TCM) that is promising in terms of diabetes management. This blog will focus on ginseng, which contains bioactives called ginsenosides . A review by Yin et al. (2008) lists the effects of ginseng on animal models and humans with type 2 diabetes. Some of the beneficial effects of ginseng are glucose lowering properties in both obese mice and diabetic humans; lowering of glycated hemoglobin (HbA1c is a biomarker of glucose control by measuring the levels of glucose attached to red blood cells) levels in type 2 diabetics, and prevention of pancreatic beta-cell death. Ginseng also prevented weight gain in mice models of obesity and type 2 diabetic humans.

Interestingly, it has been proposed that ginseng exerts its glucose lowering effects through its anti-inflammatory properties. It is proposed that ginseng inhibits the NFkB, IKK and JNK inflammatory pathways. By inhibition of the inflammatory pathways, insulin signaling (pathway that leads to the uptake of glucose into the cell) can work properly, with the overall effect of lowered blood glucose and increased insulin sensitivity.

As ginseng has both anti-hyperglycemic and anti-obesity properties, it appears to be a very good candidate for an anti-diabetic or diabetic management supplement.

Reference:

Yin J, Zhang H, Y J. Traditional Chinese medicine in treatment of metabolic syndrome. Endocr Metab Immune Disord Drug Targets 2008; 8:99-111.

Ultrasound in diagnosing Hepatic Steatosis

Hey guys.

While reading and analyzing all of the articles for this week, I found myself very intrigued by a particular method in one of them. In the article, "Young adult obese subjects with and without insulin resistance: what is the role..." I was surprised by their use of Ultrasonography and all of the essential data it is able to provide. This sparked my interest and I searched for more information on the importance of this. Whether this technique/method is "old news" or not, I had never heard of its specific use on MS and HS, and came across this piece of literature. I didn't know if any one else was as curious as I was about it, so here it is if you'd like to take a look!

See ya in class :)
- Heidi

http://www.springerlink.com/content/c0137170u2p87110/

Snake Oil? How much of our obsession with supplements is rooted in scientific evidence?

As we've discussed in class, supplements are a common go-to for health advocates. There is the obvious problem that the supplement industry undergoes no outside regulation, and we must question how "pure" and safe are these supplements. What are we putting into our bodies?
That aside, the issue of actual scientific support is more alarming to me. The fact that so many people support this industry without a backing of science is pretty shocking. However, when I think things like that, I only have to remember myself a few years ago, when I believed that if it was "natural" it couldn't do the body harm. This was a time when I also didn't understand that claims could be made without government regulation and that scientific testing of these products was actually necessary. It just seemed like "well, they made the claim, so it must be true. Why would they lie?" Now being completely enveloped in the fields of science and health, I understand the issues.
This website has a pretty interesting take on the various supplements out there and their efficacy. While it isn't a scientific article, I have to agree with a fair amount (thought not all) of what they posted based on my own extensive reading of bioactives on PubMed. I tend to enjoy visual interpretations of data/information, so if you feel the same, you'll probably enjoy this site as well. I also find it very helpful that you can gain access to the articles that the schematic is based on by clicking on the bubble. That way, you can determine if you agree or not, and it really acts as an interactive reference list. (As a side note, whoever made this website has a lot of other really interesting visuals for lots of other topics, in case you're interested).

http://www.informationisbeautiful.net/play/snake-oil-supplements/

Notice that our friend tumeric is colored brown in order to show that it looks promising. I suspect that it is located below the "worth it" line because there is very little evidence in humans thus far. Additionally, you'll see prickly pear at the very bottom of the page in the range of "no evidence." The amount of data in support of supplements is pretty clearly inversely related to the amount of supplements out there, which I would have found surprising a few years ago, and I am not at all surprised about now.

Ratio Between Fast Food Restaurants to Grocery Stores

I guess Heidi beat me to this but I also was curious about the ratio of fast food restaurants to grocery stores so I decided to do a little experiment. After class on Monday, I decided to count the number of fast food restaurants, not including sit down restaurants, and the number of grocery stores between Speedway and Campbell and Speedway and Swan. I found that there were 18 fast food restaurants, 3 ice-cream parlors, and a shocking 2 grocery stores. Surprisingly enough, neither of the 2 grocery stores were one of the 3 major chains: Fry's, Safeway, or Albertson's. The two that I past were Whole Foods Market, which as much as I love what's inside that store, it is way to expensive for the average Joe. The other was Sunflower Market which I found exactly on the corner of Speedway and Swan. Sunflower Market was surrounded by: Pizza Hut, Whataburger, Jack in the Box, and Magpies Pizza. The first thing that came to my mind was the game Monopoly, this whole situation was just a bad game of Monopoly. Secondly, I thought that there should be a law that prohibits more than I fast food restaurant per block. I found this all to be incredibly disturbing after we had discussed that in actuality, shopping at the grocery store would be cheaper than fast food. I never really thought about it that deeply, until yesterday when I saw two shows on the food network: Sandra's Money Saving Meals, and Ten Dollar Dinners which both showed how a good hearty meal could cost just $2 per person. Even the dollar menu can't provide you with a whole meal for $2, perhaps just a hamburger and fries. Anyways, so I was curious if the media had noticed this problem at all so I searched obesity and fast food restaurants on google and came across this article: http://www.nber.org/aginghealth/2009no1/w14721.html . It's called Do Fast Food Restaurants Contribute to Obesity. I found the article to be interesting, but now I'm opening the floor and want to hear what you all think!

McDonald's Vs. Groceries?

Hey everyone!

I was looking up some more information in regards to the discussion we had on McDonald's, the grocery store, and being lazy ;) This article was interesting and shocking to me because it introduces a new issue we weren't even aware of (or I wasn't, at least). McDonald's has coupons for their already reduced items! Now the Big Mac lovers have no chance of escaping this horrible and misleading trap. (sarcastic undertone) Just thought it'd be interesting to take a peek!

http://hubpages.com/hub/Fast-Foods-Are-Becoming-Groceries

Hi everyone!

Our discussion Monday had me thinking… what’s the deal with curcumin? Yeah, sure, we read an article raving about the wonders of the compound, but I was still not convinced of curcumin’s lofty guarantees. And so began my search for peer-reviewed evidence. 

Before this semester, I thought curcumin’s health benefits were scraping the bare bottom of the legitimacy jar. So I was completely awed when I had to click and scroll through hundreds of curcumin-related PubMed search results. There is no shortage of science reviews and basic articles about the topic, so I encourage you all to look through PubMed if our class article on curcumin left you as perplexed as it left me.

The point is, though, that I found the Holy Grail of class-relevant curcumin articles. Look at the title!
“Active spice-derived components can inhibit inflammatory responses of adipose tissue in obesity by suppressing inflammatory actions of macrophages and release of monocyte chemoattractant protein-1 from adipocytes.” (Woo et al.)

This article links two articles we read in class: Byron Richards’ article about curcumin AND the review about macrophage tissue infiltration written by Bourlier & Bouloumie. Because we all know a little bit about both subjects through Monday’s discussion, I figured I would show you guys this article so that you can weld your knowledge together and place a final verdict on the curcumin mystery.

As we all know, macrophages migration into adipose tissue is an underlying cause of inflammation in obese individuals. These macrophages release proinflammatory mediators into the body and chronic inflammation ensues. Woo’s experiment treated adipose tissue from obese rats with curcumin (among other spice-derived compounds) and measured the extent of macrophage infiltration and activation.

Woo’s study showed that curcumin limits the release of MCP-1 (monocyte chemoattractant protein-1). This inhibitory effect could be responsible for their observation that macrophage migration was thwarted upon treatment with the compound. If you remember from Monday, Bourlier & Bouloumie’s article suggested that macrophage migration into adipose tissue plays a huge role in obesity-induced inflammation. Woo’s article shows that curcumin has the potential to reduce these effects. Production of TNF-a and nitric oxide (pro-inflammatory mediators) was significantly impaired after curcumin treatment as well.

 Unfortunately, a huge limitation to this study is that it was not performed on humans. A huge gap of knowledge still obviously exists on the subject of curcumin and inflammation, but won’t you all sleep better tonight knowing that maybe eating that gallon of delicious Indian curry last week wasn’t an act of gluttony, but potential inflammation mediation instead?

 

References:

Woo HM, Kang JH, Kawada T, Yoo H, Sung MK, Yu R. "Active spice-derived components can inhibit inflammatory responses of adipose tissue in obesity by suppressing inflammatory actions of macrophages and release of monocyte chemoattractant protein-1 from adipocytes." Life Sci. 2007 Feb 13;80(10):926-31. Epub 2006 Nov 23.

Bourlier V, Bouloumie A. "Role of macrophage tissue infiltration in obesity and insulin resistance. Diabetes." Metab (2009), doi:10.1016/j.diabet.2009.05.001

Richards, Byron. "Curcumin: Linking Leptin, Obesity, Joint Problems, and Inflammation." News and Views. Wellness Resources, 24 May 2010. Web. 8 Feb 2011. <http://www.wellnessresources.com/main/printable/curcumin_linking_lept>. 

Fast Food Diet, Sedentary Lifestyle and Insulin Resistance

Obesity and Type 2 Diabetes (T2D) are chronic diseases, meaning they develop over a long-period of time. There is an abundance of literature on type 2 diabetics having a history of being overweight or obese, prior to their diagnosis hence, it is wise for health providers to prescribe a lifestyle modification (in terms of diet, physical activity and stress management) that is geared towards disease prevention on a long-term duration. However, we learned during the Obesity/Diabetes class discussion that fat cells (also called adipocytes) behave like immune cells, capable of responding to short-term exposure to very high amounts of glucose from high carbohydrate diets, and excessive fatty acids from high fat diets. As long-term lifestyle modification starts from baby steps, I think it is interesting to know what happens to your body, specifically, the insulin response, when a person is subject to an acute (short-term) exposure to high carbohydrate and high fat diet via fast food.

A study by Danielsson et al. (2009) investigated the effects of overeating in fat cells of lean humans. The young adult subjects (average age was 27.3 years old) were fed a high calorie fast food diet twice a day for four weeks, with restricted physical activity of 5,000 steps a day. The intervention resulted in body weight gain of 10%, and an increase in body fat of 19%. Although the subjects remained of normal BMI (of normal weight for height) at the end of the study (baseline = 22.4, end of study =24.3), they exhibited moderate insulin resistance and reduction in insulin sensitivity.

In a separate study of young men and women (average age 26 years old), a treatment group was assigned to a four week fast food diet (twice a day)plus a sedentary lifestyle of not more than 5,000 steps per day (Astrand et al., 2010). The treatment group significantly gained weight after the intervention, and similar to the Danielsson study, showed increased insulin resistance and reduced insulin sensitivity. The insulin antagonist leptin and the acute inflammation marker C-reactive protein were elevated after four weeks in the treatment group.

Although both studies had small sample sizes (less than 20 subjects in each group) they provide direct application of what we learned in class – that overnutrition can metabolically stress the body which can lead to insulin resistance.

Realistically, it may be difficult to eliminate fast food meals completely from one’s diet. However, it is important to know how the body responds to an energy-dense diet on a relatively short-term duration, so that the next time one sees a glass of a 2,000-Calorie milkshake, one can make an informed decision as to how much should be consumed or whether it is smart to drink it at all, taking into consideration your usual diet and physical activity levels.

References:

Danielsson A, Fagerholm S, Ost A, Franck N, Kjolhede P, Nystrom FH, Stralfors P. Short-term overeating induces insulin resistance in fat cells in lean human subjects. Mol Med 2009;15:228-234.

Astrand O, Carlsson M, Nilsson I, Lindstrom T, Borga M, Nystrom FH. Weight gain by hyperalimentation elevates C-reactive protein levels but does not affect circulating levels of adiponectin or resistin in healthy subjects. Eur J Endocrinol 2010;163:879-885.

Mary Jo Cantoria