Thursday, March 20, 2014

Cinti 2011 in the Annals of Medicine

So, the last paper and the first paper, hehe, we left off on was from the lab of Dr. Spiegelman. They found that there are three kinds of distinct types of fat cells in the body: classical brown, white, and the new and oh so hot, beige/brite cells. In the previous paper, they specifically focused on the beige cells and how those cells can be induced by Prdm16.

Today's paper is from Dr. Saverio Cinti. Some quick words about him, is that he is a professor at the University of Ancona in Italy. I had the pleasure to meet him one summer. ^_^ Hahaha, I don't think he remembered though. -___- But it was a great experience nonetheless! Dr. Cinti is a fantastic histologist, his papers always have wonderful histology pictures of adipose tissue. Here is a link to his university webpage: http://www.med.univpm.it/?q=node/305

Here is a quick video with Dr. Cinti explaining his research in Italian! :D



I chose his paper, because it slightly contrasts on Dr. Spiegelman's work. The hot news in the field is that there are 3 distinct types of fat cells as I have previously mentioned. Not all, however, agree with this view. I believe Dr. Cinti has a different perspective on it that we will see in his very nice review that was simple and easy to read, as well as the great descriptions of histology from electron microscopy.

You may think I have clearly chosen a side here, but I haven't! These two views are valid and are quite interesting leaving much to think about.

Since Dr. Cinti's paper is a review, I will follow a different format to tackle review papers, somewhat different than from primary research papers. Let's go!!!

1. Citation:

Cinti S (2011). Between brown and white: Novel aspects of adipocyte differentiation. Ann Med 43:104-115. 

2.  Purpose:

It is previously known that there are two types of fat cells: brown and white. The purpose of this review is to examine the evolutionary functions of these two types of fat cells, as well as a discussion on the distinct differences between them in regards to how they can be used to treat the epidemic of obesity and type 2 diabetes, and also give a survey of different fat depots in the body and where they are located. Dr. Cinti, interestingly, also touched on his view of transdifferentiation, which he has a slight different from Dr. Spielgeman.  

3. Data presentation:
(Do the authors give enough specifics for you to understand their conclusions?)


Yes, he did. This review is fill with histology pictures of adipocytes from either electron microscopy or immunohistochemical staining, which lies in line with the intent of the review, that is to examine the differences between brown and white fat cells using the method of microscopy.

I do a little bit of microscopy and tissue staining, so I'm kind of stoked about some nice figures Dr. Cinti has.


Figure 1: Light microscopy of a section where the
transition between brown (BAT) and white adipose tissue (WAT)
is visible. Note the different cytoplasmic lipid accumulation:
mostly unilocular in WAT and multilocular in BAT. Only BAT is
intensely stained by UCP1 antibodies. Bar 25 μm.


Figure 2: This is my most favorite figure in this review, because of how big the lipid droplet looks compared to the organelles in the fat cell! Electron microscopy is so beautiful, yielding such crisp images that always look like they're hand drawn to me. O_O Electron microscopy of the peripheral part of a white adipocyte. Elongated mitochondria with randomly oriented cristae are visible (arrows). N nucleus; RER rough endoplasmic reticulum; large L main lipid droplet; small L peripheral lipid droplet; BM basal membrane. 
Bar 0.7 μm.


Figure 3: Electron microscopy of cytoplasm of a brown
adipocyte. Several big mitochondria packed with cristae are
visible. L lipid droplet (some indicated). Bar 1 μm. For goodness sake, look at those cristae!!!


4. Conclusions: (What are the main conclusions from this review?)
  • There are two types of fat cells: brown (energy burning) and white (energy storage).
  • These fat cells are plastic/modifiable.
  • According to Dr. Cinti, they can convert from white to brown or brown to white depending upon the stimulus, either cold exposure or diet induced obesity, respectively. He called this conversion "transdifferentiation".
  • Macrophage infiltration is triggered by the death of fat cells and results in inflammation, which can contribute to the complications associated with obesity like type 2 diabetes. 
5. Novelty: (Do any of these conclusions represent new ideas not expressed comprehensively in the reviewed literature?)

Yes, the transdifferentiation view is very different from the work of some researchers. From my interpretation of this review, I believe that according to Dr. Cinti, there are ONLY 2 types of fat cells, brown and white. The new "beige" cells are not considered a distinct group of cells, but instead as a "transitory" cells during the transdifferentiation process. 

"In the opinion of some authors the multilocular cells expressing UCP1 — the BAT marker gene and protein — arising in the depots traditionally viewed as ‘ white ’ cannot be considered as ‘classic ’ brown adipocytes; accordingly, terms such as brite (brown to white) and beige (the intermediate colour between white and brown) have been coined for them, essentially to stress their different molecular and embryological lineage features compared with the cells found in the interscapular depot, which is traditionally considered as typical
BAT. 


We believe that such differences could reflect the presence in the tissue of cells in intermediate transdifferentiation stages and that these very elements can be responsible for the molecular differences described."

Something else novel to me from this review, is the presence of what he termed "crown like structure", when he stained for macrophages in dead fat tissue. He also used a distinct term for adipose tissue, referring to it as an organ, "the adipose organ".

6. Future directions:

He suggests that by learning more about the transdifferentiation process, inflammation (common in obese individuals) can be addressed  along with incorporating the molecules regulating differentiation (Prdm16, BMP7). 

7. Money line: 

I am beginning to think that murine adipose tissue are not the best model for studying, adipose tissue, but in the conclusion of the review he did not think that.

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