Click to listen to the audio…
Why fat burning doesn’t go according to script
The lipoprotein lipase, the enzyme that is responsible for “burning” fat, is not an independent entity, it’s activity is regulated, this regulation is done, by a family of proteins, characterized by the fact that they look a lot like angiopoietin.
Angiopoietin is a critical regulators of angiogenesis i.e. the process of making new blood vessels.
They’ve been named angiopoietin-like proteins and ascribed numbers.
There are 8 of these guys in total, but only number 3, number 4 and number 8 are involved in regulating lipoprotein lipase activity.
Too many cooks ?
3 regulators and one worker !
Sounds like a government department.
Well, LPL does need A LOT of supervising, because what the LPL is up to , depends on where it is and the overall nutritional status of the body.
Managing LPL in good times and bad
When the body has just been fed, the LPLs associated with fat cells are very busy, squirrelling away the fat that’s come in with dinner i.e. fat storing, while the LPLs associated with the heart and muscle, take it easy. When the body is fasting or running from “a lion”, the LPLs associated with fat cells take a break, because there is no need to store fat.
It’s fat burning time.
However, the burned fats, need to be assimilated, so this is when the LPL associated with the heart and muscle, must pull finger, to keep everyone adequately fuelled.
The other time LPL is deployed, is when you’re freezing your toosh off . In this scenario, the LPLs in brown adipose tissue need to get their groove on and start burning fat, to warm you up.
There are 3 levels of management involved in managing LPL : local, regional and global.
On site supervision
Turning things on
Muscle and heart cells control the amount of LPL they produce – the amount that is produced is based on their energy needs. They typically need to burn fats, at night, but during the day, regular sugar deliveries can supply most of their energy needs. Fat cells are always ready for fat storing – they have to be, it’s part of their job description.
Although fat storing is usually a day time activity.
Turning things off
This is the primary concern of the on site supervisor. The guy in charge of this is ANGPTL4. He is produced by muscle and heart cells and keeps tabs on the levels of fatty acids, coming off the triglyceride rich lipoproteins.
When he thinks they’ve had enough – he puts a stop to LPLs activity.
NOTE : This process is controlled via transcription factors and signalling happens through PPAR.
The reason for this precaution, is an oversupply of fats, in a heart cell or muscle cell, can quickly turn nasty…………
ANGPL4 not taken seriously
Fat cells don’t have any qualms about tucking into lots of fatty acids, for them, fat storing is NORMAL BIOLOGY, so they don’t need such close supervision. This is a good thing, because iInsulin and a couple of the other hormones associated with feeding, are able to override ANGPTL4 authority.
This enables fat cells to keep clearing the triglycerides from the circulation.
NOTE : Insulin can do this because he is senior management.
Supervisors based at the head office
Insulin works closely with the supervisors, ANGPTL3 and ANGPTL8, which are produced and stationed, at the body’s metabolic headquarters i.e. the liver. They work as a team, to put a stop to LPL activity and take their orders directly from insulin.
These two officials only circulate, when insulin is out and about. When insulin is not around, they stay in the office, shuffling papers.
They target LPL activity in heart and muscle cells, putting a stop to fatty acid collecting.
It turns out, fat cell LPL is a lot less responsive, to their suppression – probably because, when ANGPTL3 and ANGPTL8, show up at the front door of fat cells, they only go through the motions.
This is NO ACCIDENT. They’re following insulin’s orders.
The ultimate storage cupboard
This suits insulin. Remember insulin is in charge of putting away the groceries………….. since fat cells are THE ULTIMATE STORAGE cupboard, keeping LPL active at the fat cell interface, is ideal.
Whatever can’t be distributed to hungry cells – can be channelled to fat cells for storage !
And used later, when insulin levels drop.
Insulin is senior managment
In healthy peeps………..
Insulin levels are pretty low, most of the night.
Because, when you’re asleep, insulin is asleep too. You stop eating so grocery deliveries don’t happen and because there is no need for insulin, beta cells are able to rest and recuperate.
When you’re insulin resistant, insulin production NEVER ceases.
Insulin is high : morning, noon and NIGHT.
Fat storing 24/7
Remember ANGPTL4 is pretty lax around fat cells and although ANGPTL3 and ANGPTL8 arrive, their presence is barely noticed, thanks to insulin’s directives.
This means the fat cell LPLs attempt to flag down triglyceride rich lipoproteins all night.
It doesn’t take too long to “run out of cupboard space”.
Fat cells become unhappy and frequently throw their toys. The triglyceride rich lipoproteins, don’t get to unload their cargo and triglyceride levels rise and rise.
No worries, hungry cells can tuck in…..
Fats not favoured as a fuel source
Not really. Muscle cells and heart cells, turn balshy………….because, they are producing ANGPTL4 and he is counting fatty acids, when he thinks the cell has had enough, he puts a stop to their LPL activity. Ouch !
The triglycerides REALLY have nowhere to go.
This manifests as hypertriglyceremia.
And these unwanted fats, accumulate in “other places” – think fatty liver, fatty hearts, fatty pancreas and FAT FILLED bellies. So when all is said and done………
The “fat” problem is not really a fat problem, it’s an insulin problem.
To “fix” the fat problem, you need to do what you can, to keep insulin levels as low as possible, especially at night. To learn how, download the “WILLPOWER REPORT” here. It’s free and will give you the tools to get started.
Angiopoietin-like 4 directs uptake of dietary fat away from adipose during fasting. Molecular Metabolism (2017) 6: 809e818. Emily M. Cushing, Xun Chi, Kelli L. Sylvers, Shwetha K. Shetty, Matthew J. Potthoff, Brandon S.J. Davies
The Importance of Lipoprotein Lipase Regulation in Atherosclerosis. Biomedicines (2021) 9:782. Anni Kumari , Kristian K. Kristensen , Michael Ploug and Anne-Marie Lund Winther
Lipoprotein Lipase and Its Regulators: An Unfolding Story. Trends in Endocrinology & Metabolism (2020) 32(1):48-61. Shuangcheng Alivia Wu, Sander Kersten, and Ling Qi.
Fat can be burned or distributed & stored – where it ends up, depends on which train track, the lipid droplet is loaded onto to……..turns out, the hoghead can be bribed
The chemistry of fats is complicated. High fat levels are not because you stacked your plate with butter, meat, cream and eggs – your body made those fats.
Each droplet of fat, is carefully wrapped in bubble wrap so that the high energy fat molecules don’t cause a fire, but in obesity, you’re often “on fire”.