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Saturday, June 2, 2012

Exercise & Adipose Tissue ~ Part I: Adipose Tissue & General Relationship

From the great research group of Keith Frayn, Aging Hippie linked to this article recently:
PHYSICAL ACTIVITY AND EXERCISE IN THE REGULATION OF HUMAN ADIPOSE TISSUE PHYSIOLOGY
In composing this post, it started to get rather long so I'll break it up into parts.  I'm going to do a bullet-pointed summary and excerpts for you.  Direct quotes will be in italics, regular font is my paraphrased summary, and non-indented/bulleted text is my general commentary.

  • Cell types in adipose tissue in addition to adipocytes:  endothelial cells and fibroblast-like adipocyte precursors, macrophages and other leukocytes (particularly in obesity)
  • Adipocytes make up 80-90% of adipose tissue volme, but only 60-70% of tissue cell type
  • Fat cell turnover rates are conflicting with half-lives estimated of around a year to 8 years.
  • Mature adipocyte number appears to remain relatively constant in adulthood
  • Blood flow through adipose tissue in the fasting state is greater than that through resting skeletal muscle
  • This blood flow is highly regulated and increases rapidly with an ingested meal, especially one containing carbohydrates.
  • This blood flow is regulated in fasted state by endothelial nitrous oxide, and in the postprandial state by  β -adrenergic activity (see below).  
  • Adipose tissue is highly innervated for the sympathetic nervous system, with some evidence that this acts on adipocytes themselves, but definitely on the vasculature.  This innervation is not uniformally distributed.
  • There is debate over the presence of parasympathetic innervation.  (For a nice description of sympathetic vs. parasympathetic mouse-over HERE or click for full reference.)  
On Adipose Tissue Regulation:
    Adipose tissue triacylglycerol content reflects energy balance.  Because the body’s capacity to store glycogen is finite and relatively small, long-term imbalances between energy intake and energy expenditure are reflected in a change in the amount of triacylglycerol stored in adipocytes. Adipocyte triacylglycerol content in turn reflects the balance between the processes of fat deposition and fat mobilization. It follows that these processes must be regulated in relation to whole body energy balance. Fat mobilization is readily stimulated by β -adrenergic activation (99, 218). However, the diurnal fluctuation in fat mobilization, which is high after an overnight fast but suppressed after meals, seems to depend more on changing insulin concentrations. Local infusion of propranolol (β -adrenergic blocker) in the postabsortive state does not change lipolysis (8), although phentolamine (α -adrenergic blocker) causes a large increase, suggesting α -adrenergic inhibition of lipolysis.  However, the effect of α -adrenergic blockade may be secondary to changes in blood flow (75). Fat deposition after meals also appears largely to depend on insulin stimulation, which increases the activity of lipoprotein lipase, responsible for hydrolysis of circulating triacylglycerol (270) and increases fatty acid uptake and re-esterification in the adipocytes (69).
    Given the wealth of literature on the role of ASP in chylomicron "sensing" and clearance -- e.g. dietary fat -- from circulation, I have to say I'm disappointed that it is not mentioned.  But this wasn't a paper on dietary influences on fat tissue metabolism.  I would like to point to the bolded statement above.   The figure below comes from the article.

    There are more hormones than just insulin involved that can alter the balance of fat deposition/mobilization.  Adrenergic activity involves mainly the catecholamines adrenaline and noradrenaline (epinepherine and norepinepherine) on different receptors throughout the body.  Wikipedia has a pretty nice entry on all of this if you're interested.  So what causes "β -adrenergic activation"?  Exercise.  Yet a certain science journalist tells us exercise is useless to alter the balance of fatty acids in our adipose tissue.   But I digress ...

    Next the paper defines some terms for exercise and physical activity and some of the problems in assessing TEE (or TDEE).  They use the term PAL for physical activity level and give four examples of how PAL is highly variable and may or may not include decided "spikes" in terms of formal exercise.
    In most people, accumulated physical activity (rather than “exercise”) represents the most quantitatively important (and variable) subcomponent of physical activity energy expenditure.
    They go on to discuss why moderate exercise interventions have little effect on their own due to the small number of calories involved.

    Observational Relationships between Physical Activity and Adiposity:


    • ... in general, there appears to be the anticipated inverse relationship between measures of physical activity and measures of fat mass and distribution. 
    • Results in large studies have not been consistent
    • Cross-sectional studies don't tell us the direction of causation, e.g. does sedentary behavior cause increased adiposity of vice versa?
    • Longitudinal studies have been mixed in terms of activity at baseline and future adiposity.  Some have shown no relationship, a modest inverse relationship.
    Exercise Interventions:
    • Exercise interventions will induce a negative energy balance and consequently reduce fat mass provided dietary compensation or activity the rest of the day is not changed.
    • The magnitude of the subsequent reduction in fat mass will ultimately depend on the net energy deficit. 
    • Systematic reviews of the literature do demonstrate that exercise interventions do generally effect a reduction in body mass, albeit the size of the reductions are often small (likely due to the magnitude of the intervention/caloric deficit).
    • There is good evidence that weight loss through exercise-induced energy deficit results in loss fat mass and retention or even increases in lean mass.
    • Many interventions involving both calorie restriction and increased activity (ELMM) complicate the picture as exercise in this context does not always protect against loss of lean mass.
    I note that although this article discusses hormonal regulation of fat cells, the point is repeatedly made that fat mass is *energy balance*.  

    Part II will discuss Exercise & Fat Distribution

    12 comments:

    AgingHippie said...

    http://www.cell.com/cell-metabolism/retrieve/pii/S1550413112001891


    http://kindkehealthnotes.blogspot.com.au/2012/05/intermittent-fasting-and-diurnal.html

    Time-Restricted Feeding without Reducing Caloric Intake Prevents Metabolic Diseases in Mice Fed a High-Fat Diet

    Highlights
    Time-restricted feeding improves clock and nutrient sensor functions

    tRF prevents obesity, diabetes, and liver diseases in mice on a high-fat diet

    Nutrient type and time of feeding determine liver metabolome and nutrient homeostasis

    tRF raises bile acid production and energy expenditure and reduces inflammation

    Evelyn aka CarbSane said...

    Read about this over at Obesity Panacea ... interesting stuff and I have a few other papers on similar topic. Likely a topic for next month.

    AgingHippie said...

    http://www.salk.edu/news/pressrelease_details.php?press_id=560

    Scientists have long assumed that the cause of diet-induced obesity in mice is nutritional; however, the Salk findings suggest that the spreading of caloric intake through the day may contribute, as well, by perturbing metabolic pathways governed by the circadian clock and nutrient sensors.

    The Salk study found the body stores fat while eating and starts to burn fat and breakdown cholesterol into beneficial bile acids only after a few hours of fasting. When eating frequently, the body continues to make and store fat, ballooning fat cells and liver cells, which can result in liver damage. Under such conditions the liver also continues to make glucose, which raises blood sugar levels. Time-restricted feeding, on the other hand, reduces production of free fat, glucose and cholesterol and makes better use of them. It cuts down fat storage and turns on fat burning mechanisms when the animals undergo daily fasting, thereby keeping the liver cells healthy and reducing overall body fat.

    The daily feeding-fasting cycle activates liver enzymes that breakdown cholesterol into bile acids, spurring the metabolism of brown fat - a type of "good fat" in our body that converts extra calories to heat. Thus the body literally burns fat during fasting. The liver also shuts down glucose production for several hours, which helps lower blood glucose. The extra glucose that would have ended up in the blood - high blood sugar is a hallmark of diabetes - is instead used to build molecules that repair damaged cells and make new DNA. This helps prevent chronic inflammation, which has been implicated in the development of a number of diseases, including heart disease, cancer, stroke and Alzheimer's. Under the time-restricted feeding schedule studied by Panda's lab, such low-grade inflammation was also reduced.

    ...most successful human lifestyle interventions were first tested in mice, so he and his team are hopeful their findings will follow suit. If following a time-restricted eating schedule can prevent weight gain by 10 to 20 percent, it will be a simple and effective lifestyle intervention to contain the obesity epidemic.

    Thomas said...

    "Salk findings suggest that the spreading of caloric intake through the day may contribute, as well, by perturbing metabolic pathways governed by the circadian clock and nutrient sensors."

    How? Doesn't this all have to be taken into context of food volume? And when it is, does time restricted eating (commonly called a "feeding window" these days) really matter from a pure metabolic perspective? I'd be very surprised if it does.

    Can 1500 Kcal intake lead to weight maintenance or gain if the expenditure is 2000 Kcal per day, due to spreading this intake over the entire waking day vs. eating it all at once or in two meals (or whatever?)? Is the metabolism really that brittle?

    "When eating frequently, the body continues to make and store fat, ballooning fat cells and liver cells, which can result in liver damage."

    This is also food volume intake dependent, regardless of how often you eat.

    "Time-restricted feeding, on the other hand, reduces production of free fat, glucose and cholesterol and makes better use of them. It cuts down fat storage and turns on fat burning mechanisms when the animals undergo daily fasting, thereby keeping the liver cells healthy and reducing overall body fat."

    So does reduced food intake, regardless of how often you eat.

    It seems we are rehashing an old diet myth here.

    Gys de Jongh said...

    Thx for the article and the comment.
    It seems that there is even a direct link between the white adipose tissue and the brain...

    Metabolism. 2012 May 14.
    The sympathetic nervous system regulates the three glycerol-3P generation pathways in white adipose tissue of fasted, diabetic and high-protein diet-fed rats.
    PMID: 22592131

    Gys

    Kurt G. Harris MD said...

    I've found empirically that an 8 hour eating window works well. Nice to see some published evidence for it, even if only in rodents.

    Sanjeev said...

    They must have oversimplified some things for public consumption. Here's one

    > feeding-fasting cycle activates liver enzymes that breakdown cholesterol into bile acids

    feeding-fasted -> bile
    constant fat feeding -> ?? no bile[0]? WTH ???

    wacky wigged out fluffy fishy stuff there.

    [0] (they don't explicitly write it)

    Sanjeev said...

    This is the same study you mention in the 1st comment above?

    > tRF raises bile acid production and energy expenditure and reduces inflammation

    raises is much more plausible than activates. They thought "raises" was too complex for the public to understand and had to replace it with "activates"?

    Same comments for DNA repair & the other stuff. Who clears these smelly PR dumps?

    Sanjeev said...

    your comments were out of order in the reader so I smelled the fish before seeing the qualifications later

    ProudDaddy said...

    It would appear that "exercise ONLY makes you hungry" is nonsense, but does Frayn address the degree of "dietary compensation" in a free-feeding environment in any of his other studies?

    Any chance that Part III would address the subject of what happens to all these liberated (my word) NEFAs? In layman's terms, do they get inside muscle cells? If so, do they get inside mitochondria? If so, are they oxidized? Then, is all of that different for us, the fat-challenged?

    Stephan Guyenet said...

    I'm glad to see adrenergic signaling entering into this discussion. It's funny that there was such a stink about Taubes ignoring ASP, when norepinephrine was really the elephant in the room. Norepinephrine and insulin are yin and yang when it comes to regulating adipocyte fatty acid trafficking. Maybe Taubes ignored it because norepinephrine comes from nerve terminals that are attached to the brain, and everybody knows the brain has nothing to do with obesity?? Actually the more likely explanation is that he just wasn't aware of it.

    Evelyn aka CarbSane said...

    Hey Stephan, I think the ASP stink has a lot to do with "anything that serves to drive fat into cells and esterify it favors accumulation" thing ... coupled with the still-oft-repeated meme that you can't get fat w/o carb. It's been a year and a half since he sorta walked that back somewhat in a podcast. Clearly ASP plays a role in clearing chylo -- and I don't know where these LCHF folks think all that fat their clouding their blood with is going ;-) But yes, lots and lots of stuff about norepi & insulin, and others ... and it WAS in the biochem text books circa 2004 <-grin & tease. Moving forward, it would probably be helpful to revisit the TAG/FA cycle and perhaps treat this as two separate cycles: one inside the adipocyte, the other external between adipose, circulation/periphery, and the liver

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