Peroxisome proliferator activated receptor gamma (PPARy) is a protein that regulates the expression of genes through its heterodimerization with the retinoid x receptor (RXR) and subsequent modulation of expression of DNA (1). PPARy agonists e.g. rosiglitazone downregulate leptin gene expression (2)and upregulate adiponectin gene expression (3), thereby promoting more adipogenesis (4) and lipid accumulation.
Adiponectin, secreted by adipocytes, stimulates adipogenesis potently. It enhances adipocyte insulin sensitivity as well as glucose uptake. High levels are indicative of starvation (5). Too bad that dieting increases adiponectin, eh? Watch the weight pile back on as soon as food/insulin is there...
Talking of insulin, PPARy activation in pancreatic beta cells causes insulin hypersecretion, i.e. high insulin per unit glucose (6,7). This coupled with high adipose insulin sensitivity "PPARtitions" blood nutrition into adipocytes for storage. The insulin signalling in the adipocyte itself promotes PPARy activity through SREBP1c, thus producing a forward feedback loop of fattening.
This is thrift, why we exist today.
>>I'm really tired. Brush teeth, watch Louis CK comedy, sleep. Sounds cosy to me ;)
Bibliography
1. Wikipedia search PPAR and Youtube video search query adipogenesis
2. http://diabetes.diabetesjournals.org/content/47/4/507.full.pdf+html
3. http://www.nature.com/ijo/journal/v29/n1s/full/0802908a.html
4. http://www.jlr.org/content/46/7/1369.full.pdf
5. http://www.science20.com/news/how_adiponectin_sends_the_starvation_signal_to_the_brain
6. http://www.ncbi.nlm.nih.gov/pubmed/15561927
7. http://www.ncbi.nlm.nih.gov/pubmed/23372643
Friday, 9 August 2013
Tuesday, 6 August 2013
What is the weight of obesity? Part 1.
Most low-carb people will be 100% adamant that carbs are fucking evil and cause obesity. Most low calorie people will be 100% adamant that surplus calories are fucking evil and cause obesity.
I think both are wrong.
As humans we have evolved to store surplus lipid for long term usage and famines. That means that we will partition 50-100% of surplus energy into adipose tissue or intramuscular slow twitch tissue, depending on our genetics and our epigenetics, including gender (i.e. women with lots of oestrogen/progesterone will partition more of their calories into adipose stores).
But when this energy is stored, two things can happen:
1. Adipocytes grow in size due to enlargement of lipid droplet. More leptin and less adiponectin. Everyone is happy, end of.
2. Adipocytes grow in number due to PPAR gamma activation by adipogenic hormones, signalling pathways and genes. Less leptin, more adiponectin. More shit.
Guess which one leads to non-terminating dire grotesque 500lb obesity...
(btw it's #2)
And this is what I research on the side of my usual education (chemistry, biology, maths and french): peroxisome proliferator activated receptor gamma 2 (PPARy2) in the adipose tissue. It is the holy grail to understanding obesity and how to reverse it, because this molecule is the ultimate thrifty molecule.
When you cannot store, you burn.
When you store, you cannot burn.
Tu comprends? Good. I will continue this series, starting with what excessive PPARy does, and it ain't pretty -(think insulin hypersecretion, large adipocyte apoptosis, and overall significant increases in small, insulin sensitive, and most of all hungry adipocytes).
Just remember that food is not the culprit - the physiology is.
You won't want to miss it.
I think both are wrong.
As humans we have evolved to store surplus lipid for long term usage and famines. That means that we will partition 50-100% of surplus energy into adipose tissue or intramuscular slow twitch tissue, depending on our genetics and our epigenetics, including gender (i.e. women with lots of oestrogen/progesterone will partition more of their calories into adipose stores).
But when this energy is stored, two things can happen:
1. Adipocytes grow in size due to enlargement of lipid droplet. More leptin and less adiponectin. Everyone is happy, end of.
2. Adipocytes grow in number due to PPAR gamma activation by adipogenic hormones, signalling pathways and genes. Less leptin, more adiponectin. More shit.
Guess which one leads to non-terminating dire grotesque 500lb obesity...
(btw it's #2)
And this is what I research on the side of my usual education (chemistry, biology, maths and french): peroxisome proliferator activated receptor gamma 2 (PPARy2) in the adipose tissue. It is the holy grail to understanding obesity and how to reverse it, because this molecule is the ultimate thrifty molecule.
When you cannot store, you burn.
When you store, you cannot burn.
Tu comprends? Good. I will continue this series, starting with what excessive PPARy does, and it ain't pretty -(think insulin hypersecretion, large adipocyte apoptosis, and overall significant increases in small, insulin sensitive, and most of all hungry adipocytes).
Just remember that food is not the culprit - the physiology is.
You won't want to miss it.
Friday, 2 August 2013
Depression, Diet and (bitter) Dreams
I have damned depression: clinical, profound, tiring depression. A frank realisation that life is bleak and meaningless, that there is no point in it. Jus' livin' for teh sake of it. *Bleh*
Every single aspect of my life is affected: I have no IRL friends. My sleeping, drinking, social and eating behaviour is screwed in a horrendous disgusting fashion. I urinated six 6 times last night and I took 3 hours for sleep onset. I am *constantly* thirsty and feel like bingeing on dairy and sugar all the time.
This brings me onto something else: I eat excessive amounts of protein. WAY TOO MUCH. It's bottoming out my shit and likely exacerbating my depression because of the insulin hypersecretion brought on by too much dairy protein especially. The excessive tiredness is otherwise inexplicable other than to say that I have depression, but as a young scientist I think that label is redundant.
Everything has a mechanism, a biological explanation.
Excess protein is likely a negative thing. I eat maybe 300 grams or more per day, of which 175g may be dairy protein. This is ridiculous; I am not afraid to say that I have a dairy addiction. There are several opiate-like chemicals in dairy protein including casomorphin and lactorphin. These happen to survive digestion via whey protein's unique DDP-4 inhibiting properties so that they can bind to endorphin receptors in the brain. Temporary relief from depression, yes, but chronic worsening of my Asperger's Syndrome and general dysphoria is shit enough for me to say that I WANT TO QUIT IT, stat.
I reckon that I should be eating 150g protein, maybe 200g max. The last time I weighed myself I was 100 pounds and I stand at 156cm tall at the moment so I really don't need all that much, even if I am still growing taller. I should also note that it makes up a very high percentage of my total calories which is concerning because my insulin per unit glucose will be too high, thus producing hypoglycaemia and hypercortisolaemia. I should ideally be eating more carbohydrate and probably exercising less too.
The Plan:
>Reduce total protein to 150g-200g per day
>Increase carbohydrate to 200g per day
>Increase fat to 50g per day
The thing is I don't measure stuff out, or at least accurately, so these are ballpark figures rather than exact sciences. Bare in mind that this is a starting pt to see where this takes my mood irl.
Exercise is difficult when depressed but it results in an amelioration of my mood so it is worth it. It also kills some time, as well as improves my aesthetics slightly (I am really ugly). I will modify my exercise to 30 minutes of walking, 4k running, and 10 max sprints, plus whatever else. I may take a complete day of rest every 3 days if needs be (only walking and NEAT + may lower carb intake).
Finally I will cut out most fromage blanc and limit it to 100g per day in lieu of 1.85kg which is bloatingly high. I will eat lots of meat still, and drink 1 litre of milk for growth purposes. Chao.
Every single aspect of my life is affected: I have no IRL friends. My sleeping, drinking, social and eating behaviour is screwed in a horrendous disgusting fashion. I urinated six 6 times last night and I took 3 hours for sleep onset. I am *constantly* thirsty and feel like bingeing on dairy and sugar all the time.
This brings me onto something else: I eat excessive amounts of protein. WAY TOO MUCH. It's bottoming out my shit and likely exacerbating my depression because of the insulin hypersecretion brought on by too much dairy protein especially. The excessive tiredness is otherwise inexplicable other than to say that I have depression, but as a young scientist I think that label is redundant.
Everything has a mechanism, a biological explanation.
Excess protein is likely a negative thing. I eat maybe 300 grams or more per day, of which 175g may be dairy protein. This is ridiculous; I am not afraid to say that I have a dairy addiction. There are several opiate-like chemicals in dairy protein including casomorphin and lactorphin. These happen to survive digestion via whey protein's unique DDP-4 inhibiting properties so that they can bind to endorphin receptors in the brain. Temporary relief from depression, yes, but chronic worsening of my Asperger's Syndrome and general dysphoria is shit enough for me to say that I WANT TO QUIT IT, stat.
I reckon that I should be eating 150g protein, maybe 200g max. The last time I weighed myself I was 100 pounds and I stand at 156cm tall at the moment so I really don't need all that much, even if I am still growing taller. I should also note that it makes up a very high percentage of my total calories which is concerning because my insulin per unit glucose will be too high, thus producing hypoglycaemia and hypercortisolaemia. I should ideally be eating more carbohydrate and probably exercising less too.
The Plan:
>Reduce total protein to 150g-200g per day
>Increase carbohydrate to 200g per day
>Increase fat to 50g per day
The thing is I don't measure stuff out, or at least accurately, so these are ballpark figures rather than exact sciences. Bare in mind that this is a starting pt to see where this takes my mood irl.
Exercise is difficult when depressed but it results in an amelioration of my mood so it is worth it. It also kills some time, as well as improves my aesthetics slightly (I am really ugly). I will modify my exercise to 30 minutes of walking, 4k running, and 10 max sprints, plus whatever else. I may take a complete day of rest every 3 days if needs be (only walking and NEAT + may lower carb intake).
Finally I will cut out most fromage blanc and limit it to 100g per day in lieu of 1.85kg which is bloatingly high. I will eat lots of meat still, and drink 1 litre of milk for growth purposes. Chao.
Friday, 14 June 2013
Rumination Release: Saffy Absconds, School Completed and General Jumble
My anticipation of today was positive, optimistic and frankly unrealistic. Melancholy me... I've had a shit day. This negativity began even before the day had begun; last night my sleep latency was unusually lengthy accompanied by the typical symptoms of high sympathetic activity: sweating, excessive warmth, trembling, fidgeting, anxiety and twitching. This resulted in poor moods today and a particular pessimism only produced by insomnia.
In order to calm down last night, I grew a neuron and decided to go downstairs and take some paracetamol with K/Na solution. This proved highly effective. I encountered my cat, Saffy, who greeted me with a meow of surprise, delicacy and tones not of thought, but beyond thought.
That was the last time she has been seen... 22.5 hours ago.
Cry me a river.
The heartache throbs, hard. I ponder about where she is, then withdraw all possibilities as pessimism ensues. All I know is that she is not flattened on any local road, which is something, but the uncertainty is killing me.
Tomorrow I will initiate planning of my time and activities. I hope to mix some green tea with a can of Monster Absolute Zero. And, most of all, I want to hold my kitty :) ...
In order to calm down last night, I grew a neuron and decided to go downstairs and take some paracetamol with K/Na solution. This proved highly effective. I encountered my cat, Saffy, who greeted me with a meow of surprise, delicacy and tones not of thought, but beyond thought.
That was the last time she has been seen... 22.5 hours ago.
Cry me a river.
The heartache throbs, hard. I ponder about where she is, then withdraw all possibilities as pessimism ensues. All I know is that she is not flattened on any local road, which is something, but the uncertainty is killing me.
Dealing with Anxiety
-10g Inositol
- 40mg Zinc (- methionine) with 600mg Magnesium (- citrate)
- 2000mg KCl NaCl mixture
- 10g Glutamine
- 100mg 5-Hydroxytryptophan
- A sip of milk
- Humour/Comedy
Last Day of School
Today I had a maths exam, followed by a dismal yet hectic dose of admin fun which involved collecting signatures and queuing for England. Yes, I'm glad that I've finished another chapter of my life, but from now on life will become financially fiendish. *grumble*Tomorrow I will initiate planning of my time and activities. I hope to mix some green tea with a can of Monster Absolute Zero. And, most of all, I want to hold my kitty :) ...
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