Bursting from the seams: "Obese adipocytes" literally "explode" and leave a nasty inflammatory mess.

I just read a Public post on Facebook from someone I follow and whose blog is in my list.

https://www.facebook.com/profdrandro/posts/533941643320863

It contained a word that I've never seen before, but would like to see more often - Pyroptosis. 
See Obese adipocytes show ultrastructural features of stressed cells and die of pyroptosis.

Adipocytes dying, huh? You know what that means? Loss of body-fat. Unfortunately, there is an issue with the nasty inflammatory mess left, after adipocytes "explode". This limits the rate at which adipocytes can be "exploded".

See also SuppVersity Cellulite Special: The Etiology of Cellulite, Genetical and Behavioural Risk Factors? Physical and Supplemental Treatment Strategies & Their Efficacy. Warning! Not Safe For Work, due to pictures of naked botties.

Adipocyte Hyperplasia - Good or Bad?

First, a picture. Ignore B, C, D and E.

The above picture is Fig. 4 from Cytokine-mediated modulation of leptin and adiponectin secretion during in vitro adipogenesis: Evidence that tumor necrosis factor-α- and interleukin-1β-treated human preadipocytes are potent leptin producers.

I've posted the above picture to show that leptin secretion increases non-linearly with increasing culture period. As adipocyte content almost certainly increases non-linearly with increasing culture period (like THIS), leptin secretion almost certainly increases very non-linearly with increasing adipocyte content. As adipocyte content increases, there's no/minimal leptin secretion up to a certain level of fullness. Above this level of fullness, leptin secretion increases rapidly. What this means is that reducing adipocyte content by x% reduces leptin secretion by much more than x%.

If somebody's adipocytes become 100% full due to caloric excess, there are two extreme possibilities.

1a: If there is continued caloric excess, no preadipocytes are converted into adipocytes. There is no storage capacity available for excess nutrients, so they remain in circulation. T2DM has developed - BAD.

1b: If there is subsequent caloric deficit, adipocytes start to deplete, storage capacity becomes available and T2DM goes away (if beta cells haven't been completely destroyed in the meantime). The relatively full adipocytes secrete plenty of leptin, so metabolic rate is high and hunger is low - GOOD.

2a: If there is continued caloric excess, pre-adipocytes are converted into adipocytes. This is adipocyte hyperplasia. There is storage capacity available for excess nutrients, so T2DM doesn't develop - GOOD.

2b: If there is subsequent caloric deficit, adipocytes start to deplete. However, there are more adipocytes than in 1), so for a given fat mass, adipocytes are emptier than in 1). The greater number of emptier adipocytes secrete less leptin than in 1), so metabolic rate is lower and hunger is higher than in 1) - BAD.

Adipocyte hyperplasia is good for preventing T2DM as fat mass increases, but bad for metabolic rate and hunger after subsequent fat mass loss. I believe that growing children are much more likely to get adipocyte hyperplasia than adults. Therefore, childhood obesity is highly likely to result in misery after subsequent fat mass loss. This is why I believe that growing children should be protected from the evul greedy manufacturers of Crap-in-a-Bag/Box/Bottle (CIAB).

EDIT: Jane Karlsson just e-mailed me a link to the following study:- Adipocyte Turnover: Relevance to Human Adipose Tissue Morphology.
"Occurrence of hyperplasia (negative morphology value) or hypertrophy (positive morphology value) was independent of sex and body weight but correlated with fasting plasma insulin levels and insulin sensitivity, independent of adipocyte volume (β-coefficient = 0.3, P < 0.0001). Total adipocyte number and morphology were negatively related (r = −0.66); i.e., the total adipocyte number was greatest in pronounced hyperplasia and smallest in pronounced hypertrophy. The absolute number of new adipocytes generated each year was 70% lower (P < 0.001) in hypertrophy than in hyperplasia, and individual values for adipocyte generation and morphology were strongly related (r = 0.7, P < 0.001). The relative death rate (∼10% per year) or mean age of adipocytes (∼10 years) was not correlated with morphology."

So, if you want to remain slim, high fasting serum insulin (due to hepatic and/or muscular insulin resistance) is bad mmm-kay?

Reasons to get moving...

First, a music video. What else but...?


Part 1. Get slimmer.
Insulin increases the amount of nutrients entering adipocytes, which makes us fat and hungry.

Er, just a minute!

If increasing the amount of nutrients entering cells makes us hungry, exercise (which increases the amount of nutrients entering muscle cells) would make us hungry. It doesn't. See Fig. 1. in Influence of resistance and aerobic exercise on hunger, circulating levels of acylated ghrelin, and peptide YY in healthy males.

If going for a walk outdoors makes you hungry, you're doing it wrong. Wrap up warm, as feeling cold increases hunger. Low blood glucose level also increases hunger, so don't over-exercise while on a long-term ketogenic diet.

By the way, insulin also increases the amount of nutrients entering muscle cells.
Q. What determines the relative amounts of nutrients entering adipocytes vs muscle cells?
A. The relative insulin sensitivities of adipocytes vs muscle cells.

Adipocytes are sensitive to insulin until they become full. To reduce the amount of nutrients entering adipocytes, divert more nutrients to muscle cells by increasing their insulin sensitivity. Emptying muscle cells by doing low-intensity exercise increases their insulin sensitivity. High-intensity exercise increases their insulin sensitivity.


Part 2. Prevent/reverse age-related sarcopenia (muscle loss).
See Use 'em or lose 'em. As diverting more nutrients to muscle cells increases muscle mass, increasing their insulin sensitivity results in increased muscle mass, unless you're eating way below maintenance calories. High-intensity exercise results in more muscle mass gain than low-intensity exercise.


Part 3. Make your brain work properly.
Thanks to Chris Highcock, who gave me a complimentary copy of Hillfit, I found IL-6 and IL-10 Anti-Inflammatory Activity Links Exercise to Hypothalamic Insulin and Leptin Sensitivity through IKKβ and ER Stress Inhibition.

In plain English, this means that exercise increases both insulin and leptin sensitivity in the hypothalamus. As the hypothalamus controls appetite and both insulin & leptin are appetite-suppressing, the net result is less appetite.

Don't fight it, if you like it.

I was listening to "Scream" by Timbaland in the car today and the first part of the title made me think of dieting. Sometimes our bodies fight our every effort to change our weight. This is a particular problem for people who are trying to lose weight. They feel cold, hungry & listless and they really want to EAT SOMETHING, damn it! It's because they are trying to change their set point weight. For information about set point weight, see Good Science: Dr. Leibel Explains Metabolic Slowdown with Weight Loss.

The problem with getting fat is that adipocytes (fat cells) can only hypertrophy (become larger in size) so much. When they reach a certain size, they secrete something (I don't know how this works so don't ask) that stimulates preadipocytes to become adipocytes. A larger number of something is called hyperplasia. Once adipocyte hyperplasia has occurred, we are stuck with them for life depending on what part of the body they've formed in. Visceral fat (the harmful fat around your internal organs) cannot be removed by liposuction. Only sub-cutaneous fat can. Losing weight & bodyfat results in adipocytes becoming smaller. However, the more of them there are, the smaller they have to become to achieve a given fat mass.

Adipocytes secrete leptin, the amount secreted reducing with reducing size. Leptin works by inhibiting the activity of neurons that contain neuropeptide Y (NPY) and agouti-related peptide (AgRP). Reducing serum leptin level acts on the hypothalamus, increasing our appetites and reducing our energy expenditures. When adipocytes become smaller than normal, leptin secretion reduces considerably and even though there are more of them, net serum leptin decreases and the end result is feeling cold, hungry & listless.

There's another problem that can occur with leptin. In the above example, there's a lack of leptin and the body doesn't work properly. This is analogous to type 1 diabetes. In some people, the hypothalamus becomes insensitive to leptin. Leptin resistance is analogous to type 2 diabetes in that the stuff's present at the correct level but it doesn't have the desired effect and the body doesn't work properly. The end result is also feeling cold, hungry & listless.

It's supposedly possible to restore the sensitivity of the hypothalamus to leptin, but that's for another blog post. So a fat person could say "I'm not fat, I'm hypothalamically-challenged!"