Fat cells: Is it the size or the number?

Obesity is tightly associated with virtually all "western diseases," including high blood pressure, diabetes, gout, and dyslipidemia.  Insulin resistance (type 2 diabetes) is similarly associated with these diseases.  This is why researchers have begun to use the literary gem and public health nightmare "diabesity" when referring to our current health epidemic.  Thus, researchers are diligently trying to tease apart the associations and mechanisms that explain diabesity.
  
Veilleux and colleagues published a study in this month's issue of Diabetes looking at the predictive power of the size and number of adipocytes (fat cells) on markers of dyslipidemia ("poor blood lipids").     They found that the enlargement of abdominal adipocytes was independently associated with changes in blood lipids consistent with the metabolic syndrome.

Source: flickr

Above is a photomicrograph of adipocytes.  The dark splotches are the nuclei of the cells.  The big white space?  That's a large lipid droplet.  Adipocytes store fat to be used for energy, and as you can see, they are very good at what they do.  Our fat stores can increase by either enlargement of the adipoctyes or an increase in the number of adipocytes, or as is common in biology, a combination of the two. And all of these cells aggregrate to form different fat depots in the body.  

    

Two of the main fat stores are subcutaneous fat - meaning under the skin - and omental fat, which rests behind the abdominal wall.  The gynoid, or "pear shape," fat distribution refers to subcutaneous fat distributed around the hips and buttucks, and it is associated with a decreased risk of dyslipidemia.  Android, or "apple shape," fat distribution refers to abdominal obesity, and is associated with an increased risk of dyslipidemia.  But remember, a large gut is composed of both subcutaneous fat and omental fat; both tend to increase together but it is the omental that seems the most deleterious.

Abdominal subcutaneous fat
Source: FreeDigitalPhotos

Peripheral subcutaneous fat
Source: FreeDigitalPhotos

Given the known complications of body fat, researchers wanted to look to see if the association between omental fat and dyslipidemia was more closely related to enlarged adipocytes or a higher number of adipocytes, independent of fat distribution or fat mass.  Obese women who were undergoing surgery had biopsies taken of their omental and subcutaneous fat.  These biopsies were then used to categorize the women by adipocyte hypertrophy (enlargement) or hyperplasia (high cell count) for both subcutaneous and omental fat stores.  Blood markers for dyslipidemia - particularly representing hypertriglyceridemia, or elevated triglycerides, were then coupled with the adipocyte data to develop a predictive model - that is, how do adipocyte characteristics predict dyslipidemia.

The most pronounced finding was that sufficiently large omental adipocytes increased the risk of hypertriglyceridemia by 4-fold, whereas sufficiently many omental adipocytes only increased the risk by 1.5-fold.  The size or number of subcutaneous adipocytes showed no increased risk of elevated triglycerides.  These changes in risk were seen after several factors had been adjusted for - such as body fat mass, BMI, and others - and so represent the independent contribution of these adipocyte characteristics.  The enlarged omental adipocyte group further demonstrated dyslipidemia in other triglyceride-related blood markers, although the results were less dramatic.

Figure: Conceptual representation of the results

And perhaps you are wondering, do enlarged omental adipocytes cause the dyslipidemia?  Does the dyslipidemia cause the enlarged adipocytes?  Or is there something else that causes them both to occur in lockstep?  An interesting piece to the puzzle is that surgical removal of omental fat does not improve dyslipidemia.  Or only seems to do so in the short-term when it is accompanied with the already-shown-to-do-so gastric bypass surgery (article on recent findings).  Those data would indicate that it is not the omental fat that causes the dyslipidemia.  But given the Veilleux study we just discussed, perhaps surgical removal would work if the patients had predominately large omental adipocytes, rather than many.  

While it's well known that obesity is tightly associated with dyslipidemia and metabolic syndrome, these data are the first to specifically examine adipocyte "cellularity" with metabolic derangement in obese women.  Admittedly, this experiment is more interesting from a physiological or mechanistic standpoint - everyone knows that abdominal obesity is both unhealthy and no one is happy with their "gut" regardless of the cellular mechanism.  So while we wait for that eventual discovery, let's agree to keep our visceral fat cells both small and few.

Omelet with Berries, or, the Low Carb Pancake?

     I had breakfast with my mom this morning, and in good form, we had a low carb - "whole food" sort of meal.  We have been meaning to try one of her long-lost recipes that she realized would be great for low carb eating.  I do not know quite what to call it, but it is simply eggs served with sour cream and berries on top.  It is essentially a low carb pancake.

     My mom learned about this recipe from a diner back in Minnesota and it was originally served with strawberries.  I generally do not like to eat low carb version of carb-heavy meals (low carb "x").  I prefer meals that are inherently lower in carbs or that easily translate.  "Low carb lasagna," which is layers of spinach, vegetables, meat, and cheese is not lasagna and just does not quite do it for me.  I prefer to have meals such as lasagna as a Saturday supper or a celebration food.  But it is nice to find alternative-like meals.

     While this meal is reminiscent of pancakes or crêpes, it really is it's own thing.  It has a certain Bon Appétit flare, or dare I say sophistication.  It would be excellent (egg-cellent?) for brunch.  But I see it as a weekend meal that can fulfill that Saturday morning pancake craving.

Egg Pancake with Fruit

1. Whisk one or two eggs with cream and a small pinch of salt.
2. Fry egg in butter - stir egg initially to create lumps of cooked egg, then cook flat.
3. Flip once and cook until just finished - although the girlfriend would prefer well done ;)
4. Spread sour cream, top with fruit, and sprinkle a dash of Splenda or even sugar.  Or no sweetener!

     We served it with bacon and split an orange from the backyard.  Oh!  And we had peaberry coffee that was gifted to me by some friends who recently visited Kauai.  Remember, "low carb" doesn't mean "no-carb."  So always remember, a breakfast like this has plenty of variety, and is more nutrient dense than a bowl of even the most whole-grain cereal.  

Good morning!

Kidneys and Ketones.

     When you shuffle thorough various low carb or nutrition blogs, you can't help but feel the splash of a new low carb diet study.  Especially when media generate headlines such as "Low carb, high fat diet could replace dialysis."  While it would have been prudent for MSNBC to clarify that this may end up only applying to mice, the results are still news worthy.  

     The work was conducted by researchers at the Mount Sinai School of Medicine in New York, NY. They investigated the effect of diet, specifically a ketogenic diet, on nephropathy in diabetic mouse models.  To many people, this may seem to be a paradoxical diet to study in diabetics - perhaps ketoacidosis comes to mind - but it looks to have potential.

Source:  OpenClipArt

     Nephropathy refers to damage of the kidneys and is a known complication of diabetes.  Prior to the advent of insulin therapy, type 1 diabetes (absence of insulin) caused a very short life expectancy.  However, as insulin allowed type 1 diabetics to live much longer lives, and as more and more people are becoming type 2 diabetics (insulin resistant), these individuals are living with long-term exposures to relatively high blood sugar.  Fortunately, the standard of care is to maintain blood glucose as near normal as possible, which has been shown to reduce - although not eliminate - complications of hyperglycemia.  These researchers had a hunch that there could me an additional strategy for reducing complications, and perhaps even reversing it.
     While working on other experiments, the researchers noted that ketones produced a molecular action that could benefit diabetic patients.  They also demonstrated that ketones directly reduce the oxidative damage induced by bathing neurons in a glucose solution.  Given that the ketogenic diet shifts cell metabolism away from glucose utilization and towards fat and ketone utilization,  they hypothesized that a ketogenic diet would protect against the hazardous effects of chronic hyperglycemia.
     The study used eight groups of animals:  four groups of normal "wildtype" mice, two groups of Akita mice (type 1 diabetes model), and two groups of leptin receptor knockout mice (type 2 diabetes model - see image).  All groups were placed on a control "chow" diet (high carb, low fat, moderate protein) until the diabetic models developed nephropathy; then two control groups and one group from each model were switched to a ketogenic diet (very high fat (87%), low carb and protein) until the end of the study.  The researchers then assessed blood markers, gene expression, and kidney histology for nephropathy.

Left is "wild type," right is db/db mouse.
Source:  ncbi.nlm.nih.gov

     The most impressive finding is that the elevated albumin-to-creatnine ratio (ACR - a marker for nephropathy) found in the chow-fed diabetic models was abolished in the ketogenic counterparts - a complete reversal of the marker (see figure below).

Source: PLoS ONE

     The ketogenic diet appears to blunt or completely reverse the oxidative or other stress mediated gene expression seen in the pathogenic mice.  These "functional" findings are the most impressive, but the study also showed a partial reversal of the histological damage in the kidneys; given more time, this could conceivably mean that a return to near or total anatomical normality may occur.  The idea that ketones greatly benefit diabetics may seem paradoxical, but it isn't so simple.
     When people talk about the Atkin's Diet - a ketogenic diet upon initiation - they invariably make the association to ketoacidosis in unchecked diabetes.  However, ketoacidosis is a consequence of systemic cellular starvation in the absence of insulin, which leads to an unregulated release of ketones into the blood that eventually turns the blood acidic.  Ketosis is a physiological elevation of ketones from fat metabolism in the absence of glucose and produces benign levels of ketones in the blood.  Despite the distinction, the connection between ketones and kidney protection is not obvious. 
     This study offers a proof of concept that some nutrition strategies can at least begin to reverse a disease process such as nephropathy.  While there is no question that this may not work in humans, or if anyone is sure that enough patients would maintain a ketogenic diet long enough to invoke an improvement, these finds are compelling.  Perhaps they will find other potential therapies using cream, eggs, and bacon.

Gary Taubes's article on sugar

Taubes has written another article that I wanted to share.  This one discusses sugar consumption - separately from carbohydrate consumption - and some real and potential consequences of it.  There is not enough evidence to conclude that sugar is as detrimental as some purport it to be; but it is categorically true that refined sugar (or naturally attained sucrose for that matter) is non-essential in the human diet.  In that respect, it's easy to draw some parallels with something like alcohol.

What do you think?  Is Sugar Toxic?

Some recent eats... before I post about aerobic exercise and diet.

Weekend breakfast with the girlfriend.  Veggie omelets topped guacamole, bacon, and strawberries on the side.

Weekend dinner with the friends.  BBQ beef ribs (pictured) with sweet potatoes and sautéed kale.  Hard not to enjoy such a colorful dinner.

Dinner this week.   Fried grass-fed hamburger with aged Gruyere and avocado (half of a giant one!).  I stocked up on quite a bit of Trader Joe's organic beef.  I appreciate that their organic variety is also grass-fed...rather than simply organic corn feed.

Veggies with a homemade dill ranch dressing.

Noting wrong with dinner and science (see books in the distance).  

The wine was left over from Sunday and I couldn't let it go to waste...

Civil Eats: Where do Americans get their calories?

I am busy this week crunching data for a potential research abstract, so I thought I would send in a blog substitute for today.  Check out this post by Civil Eats.

It has a really neat info-graphic that shows America's estimated per capita calorie consumption from various food groups between 1970 and 2008.  I find what we're eating to be more telling than how much.

The major limitation of this data is that it is derived from USDA food availability statistics and not from samples of what individuals actually consume.  While they have adjusted for grocery store waste, they have not adjusted for restaurant waste.  This could mean that all the oil leftover in deep-fryers is estimated into the consumption statistics.

Added sugar appears to have risen about 20%.  Meat, egg, and nut consumption has gone unchanged.  Grain consumption inflates in the 1980's (fear of fat trend?), and added fat inflates between 1990's and 2000's.  From this data, I find it hard to blame the consumption of animal products as a cause of our current dietary tribulation, so I'm maintaining that sugar and flour are the problems.  

Bison/Beef bone broth

Dinner this past week was accompanied by homemade bone broth.  It's my celebration of obscure grass-fed cuts of meat from the farmer's market.  I used bone-marrow bones and neck bones.  Cuts that are primarily bone are essentially scraps and are much cheaper than steak cuts.

First, I roasted the bones at 400 degrees Fahrenheit for about 20 minutes.

Meanwhile, I chopped up some celery, carrots, and onion.  I had some pre-chopped garlic on hand, so that cut a step (pun intended).

 

I removed the bones from the oven and made sure they had a nice roasted-brown color.  I had to be careful with the marrow bones as the fatty marrow can easily burn if left unchecked.  

I added the meat, vegetables, and 10 cups of water to my slow cooker.  I used parsley stems, a bay leaf, salt, and whole peppercorns for a bit of an accent.  I left the ceramic bowl in the fridge overnight, and simply put it in the slow cooker before leaving for the lab in the morning.

After cooking for ten hours, the broth was rich and the meat and vegetables were tender.  I strained the broth and ate the meat and vegetables.  And I definitely did not skim off the fat.  I paid a premium for what relatively little fat is left on the grass-fed meat!

A hot cup of broth is perfect for washing down roasted meat.  Just like an Inuit would!