Monday, 25 June 2012

Adipocyte Hyperplasia - Good or Bad?

The answer is "yes". Firstly, a picture:-


The above picture is from Fig. 4 of 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 volume almost certainly increases non-linearly with increasing culture period (like THIS), leptin secretion almost certainly increases very non-linearly with increasing adipocyte volume. As adipocyte volume 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 volume by x% reduces leptin secretion by much more than x%.

If somebody's adipocytes become 100% full due to caloric excess, there are two 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 more likely to get adipocyte hyperplasia than adults. Therefore, childhood obesity is likely to result in misery after subsequent fat mass loss. This is why I believe that growing children should be protected from being manipulated by the persuasive marketing of greedy manufacturers of CIAB (Crap-in-a-Bag/Box/Bottle).

According to 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."

If you want to remain slim, high fasting serum insulin (due to hepatic and/or muscular insulin resistance) is bad.

Monday, 18 June 2012

Hyperinsulinaemia and Insulin Resistance - An Engineer's Perspective.

Another techie post.
From https://en.wikipedia.org/wiki/Negative_feedback_amplifier
There's been some arguing discussion over whether Hyperinsulinaemia (HI) causes Insulin Resistance (IR). My answer is...Yes and No.

HI increases IR, long-term. See Downregulation and upregulation: The Insulin Receptor and Insulin oscillation.

HI doesn't increase IR, short-term. How can I claim this? The above diagram represents a Negative Feedback (NFB) control system, which is how Blood Glucose is regulated.

"Input" represents Glucose from digested sugars and starches. The arrow pointing at AOL represents Blood Glucose (BG). The triangle containing AOL represents pancreatic beta cells. "Output" represents Insulin Secretion (ISec). More BG = More ISec.

The box containing ß represents three things that work in parallel to reduce Blood Glucose.
1) The Liver. More ISec = Hepatic Glucose Production rate decreased.
2) Muscle mass. More ISec = Glucose intake to Muscle mass rate increased, via Glu-T4.
3) Fat mass. More ISec = Glucose intake to Fat mass rate increased, via Glu-T4.
The three things aren't of equal strength, but they provide overall negative feedback.

If overall negative feedback is halved due to doubling of overall IR in the above three paths, ISec doubles. If you don't believe me, see Idealised Negative Feedback Inverting Amplifier using an idealised op amp on WolframAlpha. Double the value of resistance 2 (the negative feedback resistor R2). and the output voltage on the inverting amplifier doubles from -10V to -20V.

The idealised Negative Feedback Inverting Amplifier using an idealised op amp on WolframAlpha is interesting in that an idealised op amp (the triangle with + and - inputs) has infinite gain and infinite voltage on its power supplies. As a result, there is zero volts (output voltage divided by infinity) between the idealised op amp's + terminal and its - terminal. If the idealised op amp's + terminal is connected to 0V (a.k.a. "Earth"), its - terminal is at 0V (a.k.a. "Virtual Earth") and has zero variation, whatever the input voltage. An actual op amp has a voltage gain of ~140dB (~10,000,000), so an output voltage of -10V can be achieved with a voltage of 1uV (one millionth of a Volt) on its - terminal.

If pancreatic beta cells had a zero threshold and infinite gain like an idealised op amp, BG would be zero and have zero variation with varying Glucose input. Pancreatic beta cells actually have a positive threshold and low gain, so BG is positive and has significant variation with varying Glucose input.

If ISec becomes zero (as in type 1 diabetes), there is zero negative feedback and BG goes up a lot. The same thing happens to the voltage on the idealised op amp's - terminal if its power supplies are 0V instead of infinite.

If ISec becomes insufficient (as in type 2 diabetes), there is insufficient negative feedback and BG goes up a bit. The same thing happens to the voltage on the idealised op amp's - terminal if its power supplies are 5V.

Having established that ISec is proportional to overall IR, what would happen if overall IR was proportional to ISec? If ISec doubled, overall IR would double, which would double ISec, which would double overall IR, ad infinitum. ISec would increase to maximum instantly. THIS DOESN'T HAPPEN. Therefore, IR doesn't increase in proportion to ISec, short term.

Long-term, increased ISec increases IR for a variety of reasons, one of them being that increased ISec increases the rate at which cells fill with glycogen. Once full of glycogen, cells must down-regulate their intake by down-regulating Glu-T4 and Glu-T2 (fat and liver cells also up-regulate their output of stuff) or burst.

So, deplete your cells of glycogen by eating a diet that results in you unconsciously eating less and moving more. Also, do some higher-intensity exercises. Chris Highcock emailed me a link to Muscular strength and markers of insulin resistance in European adolescents: the HELENA Study.

Friday, 15 June 2012

Weird Filters.

Here's a weird picture.
Why is it that some people see the world through weird cognitive bias filters? It makes discussion with them impossible, as what I write is remixed with weird filters into something completely different. They then argue against something completely different, not what I wrote. This is the classic Straw Man argument.

Here are some examples of remixing with weird filters, taken from Insulin, the Un-dead and coffin nails.

1) ""A" is..." is remixed into "I believe that "B", "C", "D",..."Z" do not exist".

2) ""A" is caused by "B"" is remixed into "A is only caused by "B"". This is similar to 1).

3) "As cells are emptied (of glycogen)..." is remixed into "Once cells are completely emptied (of glycogen)...". The "As" at the beginning of the sentence signifies an ongoing process. Next time, I'll write "As cells are depleted (of glycogen)..." EDIT: Rewritten using c/p'ed text.

4) The statement "eating too much and moving too little" is remixed into "Gluttony and Sloth". Gluttony and Sloth are conscious actions. Eating too much due to ravenous hunger and moving too little due to lethargy/sleepiness are unconscious actions. Anybody who thinks that I mean/insinuate the former rather than the latter is an idiot/insane.

Having remixed what I wrote into something completely different, I am then accused of intellectual dishonesty. Oy!

Wednesday, 13 June 2012

Dirty Rotten Scoundrels.

Who, these guys?
From http://www.bbc.co.uk/programmes/b00kz6jc

No. I'm referring to Manufacturers of Crap-in-a-Bag/Box/Bottle (CIAB), or MOCIAB for short.

In Obesity is multi-factorial, spectra and other stuff, I mentioned Mayor of NYC Michael Bloomberg's ban on the use of cups larger than 16oz for the sale of sugary sodas. Note that Mayor Bloomberg is not trying to ban sugary sodas or tax anything. People are still free to buy as many cups of sugary soda as they want. However, the whining from people is deafening!

Surprise, surprise! MOCIAB have retaliated with the usual dirty tricks.

1) Lies, damned lies and MOCIAB statistics.
Cherry-picked studies, much?
2) Have a number of MOCIAB/pro-MOCIAB groups/sites drown-out good advice with bad. This is a standard marketing trick pioneered by Edward Bernays. Some examples of MOCIAB/pro-MOCIAB groups are:- Academy of Nutrition and Dietetics, http://www.ameribev.org/, http://www.consumerfreedom.com/, http://www.letsclearitup.org/ and http://www.livepositively.com/.


In Psychological manipulation, there was a link to a story about a hypnotist who used his freedom of speech to influence women into "freely" handing him cash. So, why is he not allowed to use his freedom of speech to influence people (Italian police were hunting him) whereas MOCIAB are?

EDIT: I'll repeat it here, in case you missed it in the other post. Confessions of a former Dirty Rotten Scoundrel.

Saturday, 9 June 2012

Health, wealth and happiness.

Uh-oh! Another title with three items.
The Three Stooges in 1938's Healthy, Wealthy and Dumb. L to R: Moe Howard, Curly Howard, Larry Fine
Which of the three things in the title is the most important?

I run a health blog, so you don't need to be a rocket scientist to guess my opinion. Health. As I mentioned in "The Diet Debacle" debacle, you are what you eat i.e. if you eat/drink rubbish, you get a rubbish body. Therefore, what people eat/drink is important in order to maximise their health.

Should "food" manufacturers (whose prime objective is to maximise their profits) have the right to unduly influence people's food choices (which results in them experiencing deteriorating health) by using cunning marketing methods? I say "No".

Should "food" manufacturers have the right to unduly influence politicians into subsidising the raw ingredients of their "food" by bribery lobbying? I say "No".

It's been argued that "food" manufacturers should have the right to free speech. I disagree, as the motives of a "food" manufacturer are completely different from the motives of an individual.

I'm not asking for a ban on the marketing of non-food items or a ban on government subsidies for non-food items. Am I really asking so much?

The above are moot points, as "food" manufacturers and governments are very powerful, and nobody wants to give up power. Therefore, nothing much will change unless you people out there can persuade other people to do what you are doing by leading by example, and so on. If enough people stop buying "food" (and I'm using quotes deliberately, as a lot of "food" isn't fit for pig-swill, let alone human consumption) and start buying, cooking & eating real food, some "food" manufacturers might experience such a large drop in profits that they go out of business.

Friday, 8 June 2012

A comment, a simile and insanity.

A lot of my recent titles contain three items.

1) The comment: I'm just about to leave the following comment on Peter (Hyperlipid)'s blog post Insulin and the Rewards of overfeeding. I thought that it was so good at summing-up, I'll post it here first!

"All,

Insulin increases the amount of glucose & FFAs entering fat cells, muscle cells & the liver.

Insulin decreases the amount of glycerol & FFAs exiting fat cells & the amount of glucose exiting the liver.

Hyperinsulinaemia (which can produce sedation) results when one or more of the following tissues loses insulin sensitivity:- fat cells, muscle cells & the liver.

So, why do people keep saying that hyperinsulinaemia locks nutrients away in fat cells only, thus robbing other cells of nutrients, thus causing lethargy?

The relative insulin sensitivity of tissues determines the relative partitioning of nutrients into those tissues.

When tissues lose sensitivity to insulin, blood glucose control becomes impaired. This results in roller-coaster blood glucose levels after eating high-glycaemic carbohydrates. A rapidly-falling blood glucose level causes ravenous hunger. I have experienced this during medically-monitored tests (OGTTs & an insulin shock test).

Low-carb/ketogenic diets don't result in a roller-coaster blood glucose level and therefore don't cause ravenous hunger. Simples!

Overeating due to ravenous hunger is NOT gluttony, just as under-moving due to sedation is NOT sloth.

THIS is gluttony."

EDIT: This didn't go in my comment but should have:- "Low-carb/ketogenic diets result in the avoidance of moreish & calorific foods such as sweets, chocolate, cake, biscuits, pizza, Pringles etc. A single bite of such foods has a negligible effect on blood glucose & insulin levels, but encourages another bite and another and another ad nauseam, due to Food Reward.


2) The simile: I use similes. I used the simile "As happy as a pig in shit" in a comment somewhere on Woos blog. Now, you may (or may not) have noticed that my user-name is Nigeepoo. We Brits are obsessed by two things - The weather and our bowel movements. I find things to do with poo and farting amusing (schoolboy humour, I know!). I used the simile "As happy as a pig in shit" because it is amusing.


3) The insanity: According to Woo in the following comment:-
"Re: the comment...Sorry, not convinced.
You are basically refusing to admit your choice of words implied moral judgement. The phrase "happier than a pig in shit" is always applied to examples of people being content in immorality/bad behavior particularly gluttony and sloth... unless it is used ironically. Only an autistic or a non-english speaker would believe this crap."

Woo, you are as mad as a March hare. IMO of course, like everything I write. Duh!

Tuesday, 5 June 2012

"The Diet Debacle" debacle.

What's that funny smell?

According to Robert H. Lustig in The Diet Debacle,"If a calorie is a calorie, then any food can be part of a balanced diet; and, if we are what we eat, then everyone chooses what they eat."

Firstly, the first nutritional maxim isn't "A calorie is a calorie". It's actually "Where bodyweight is concerned, a calorie is a calorie". Leaving out the first four words makes a huge difference to the meaning.

Secondly, the second nutritional maxim actually means "Your body is made out of what you eat. Therefore, if you eat/drink rubbish, you get a rubbish body.

Apart from that, the rest of the article is absolutely fine*.

*The above sentence ending in "*" is pure irony. See also Review & Critique: The Skinny on Obesity ~ Intro and Part I and Review & Critique: The Skinny on Obesity ~ Part II Sickeningly Inaccurate.

The sad thing is that I actually sympathise with Robert H. Lustig's aim, which is to reduce the humongous amount of sugar that Americans shove down their throats in solid or liquid form each year.

I don't want to come across as a Socialist Asshole (it's Arsehole, Sean!), but intervention is sometimes needed to stop certain humans and groups thereof (e.g. companies/corporations) from harming other humans and groups thereof (e.g. the general population).

In City of New York Bureau of Food Discipline, Sean wrote "Never mind that the record of government diet intervention is abysmal, this time it will work." I can't speak for the US, as I don't know how things work over there. Here in the U.K, DEFRA aims to maintain standards in the way that crops are grown and in the management of farm animals. The FSA aims to maintain standards for food safety, although they do occasionally issue some dubious nutritional advice (read the comments to see some familiar names).

Just because government agencies occasionally cock things up, does that mean that we should have zero government intervention where food is concerned? I obviously think not!

See also What Is Food? and Former Coke executive slams ‘share of stomach’ marketing campaign.

Addendum: If (as I believe) corporations should be prevented from unduly influencing the general population in their food choices by banning all advertisements for foods & drinks, then governments should also be prevented from unduly influencing the general population in their food choices by banning food policies and crop subsidies. All that governments should do food-wise is enforce food safety standards.

Saturday, 2 June 2012

Of mice and men, Kleiber's Law & FIRKO.

More musings from my fevered brain!

I remembered a discussion on Hyperlipid about FIRKO mice.

Note: FIRKO stands for Fat Insulin Receptor Knock Out and it results in White Adipose Tissue (WAT) having vastly reduced uptake of nutrients, thus inhibiting gain of WAT. Brown Adipose Tissue (BAT) has up-regulated uncoupling proteins i.e. BAT produces more heat. See also Research data concerning maximum life span.

What was also interesting was that, in a study where mice's VMH (VentroMedial Hypothalamus) was also deliberately damaged, mice ate more food but didn't gain any weight. What? The Energy Balance Equation doesn't apply?

Mice weigh very little (~30g), so they can't burn off significant amounts of energy through exercise the way that humans can. So, how on Earth can mice eat more without gaining any weight?

Peter Dobromylskyj gave me the answer. As a veterinary surgeon, he works on rodents, so he knows about this. Rodents under anaesthesia easily get hypothermia. The penny dropped! Mice have a very high surface area to mass ratio (see the above graph) compared to adult humans. As heat is lost through the skin, small animals like mice are at a disadvantage when it comes to heat conservation. They have behaviours for conserving heat e.g. covering themselves in bedding (which reduces heat loss) or huddling together in groups (which reduces overall surface area to mass ratio). Anaesthesia prevents these behaviours.

Any excess energy intake that cannot be stored due to FIRKOisation is disposed of by increased heat production in BAT and increased heat loss by reduced heat conservation behaviours. Simples!

Most adult humans have very little BAT, so they are unable to perform the same trick. If a human raises their metabolic rate significantly (say, by taking 2,4-Dinitrophenol), they tend to overheat & die.

You could try sitting in a bath of cold water. ;-p That would make me really cold and hungry (and wet!), so I would eat ravenously afterwards. But that's me. Your Mileage May Vary.

Obesity is multi-factorial, spectra and other stuff.

This post is a hotch-potch of thoughts that are currently whizzing around in my brain.

1) Obesity: Like just about everything in life, obesity is multi-factorial. Each factor may have only a small impact on obesity. Tackling one factor alone won't solve the problem. Every factor has to be tackled, one at a time.

So, New York City Mayor Michael Bloomberg announcing a ban on sales of sugary drinks larger than 16 ounces in restaurants, delis, sports arenas, and movie theaters won't solve the obesity problem, but it will help.

EDIT: In shops and supermarkets in the UK, tobacco products now have to be kept out of sight. I'd like to see the same thing happen to Crap-In-A-Bag/Box/Bottle (CIAB).

2) Spectra: As also mentioned in my first link, there is a spectrum of fatness in the general population which probably follows a bell distribution curve. From skinniest to fattest, there are people who are:-
Extremely skinny. Very skinny. Skinny. A bit skinny. Average. A bit fat. Fat. Very fat. Extremely fat.

If you take somebody in a category who isn't currently consuming CIAB and introduce CIAB to their diet, what happens? They move to a category to the right. Therefore, it's possible for there to be very skinny people who consume CIAB. Therefore, anybody who (or should that be Wooo?) states that the existence of very skinny people who consume CIAB is proof that Food Reward doesn't exist is wrong.

3) Other stuff: I am concerned with people overlooking postprandial (a.k.a. nonfasting) triglycerides (a.k.a. triacylglycerols a.k.a. TAGs a.k.a. TGs) after eating large amounts of fat. According to Fasting Compared With Nonfasting Triglycerides and Risk of Cardiovascular Events in Women, serum TGs 2-4 hours post-meal are very significantly associated with Cardiovascular Events (fully adjusted hazard ratio [95% confidence interval] for highest vs lowest tertiles of levels, 4.48 [1.98-10.15] [P < 0.001 for trend]).

After 4 hours post-meal, serum TGs are cleared from circulation by being burned by muscles and/or by being stored in fat cells. See Figure 3B in Extended effects of evening meal carbohydrate-to-fat ratio on fasting and postprandial substrate metabolism.