every exercise physiologist knows that exercise is completely useless for weight loss. If exercise was effective for weight loss there would be no humans because our ancestors would have starved to death a couple of million years ago. We lose 80% of our energy intake as heat. So wearing fewer clothes is a vastly more effective way to lose weight than exercise.
Thursday, 29 March 2012
Wednesday, 28 March 2012
The receptors that dopamine acts on in the brain sends a signal down the nervous system much like electricity down a copper wire to the targeted group of fat cells, whereby some triglyceride is subsequently kicked out of the central lipid droplet and is then chopped up by lipases in the cytoplasm, breaking it down to fatty acids + glycerol.
Much attention is often paid to the circulating factors in the blood that influence fat cell size, like insulin, acylation stimulating protein, epinephrine etc etc. But the connection of fat cells directly to the brain by the nervous system is often overlooked, And this connection is also reported to be a major source of lipolysis.
This paper talks about the Siberian Hamster that is seasonally obese, it is fat in the summer when the days are long and lean in the winter when the days are short. The brain is able to keep track of this seasonality by the duration of the nocturnal secretion of melatonin. However, melatonin itself does not stimulate lipolysis when cultured with fat cells.
Despite much investigation into the blood circulating hormones that where known to affect fat cell size, none of them were able to account for the dramatic change in bodyfat seen in the Hamster in response to season changes. The logical conclusion from this was that seasonal obesity was almost completely controlled by nervous system lipolysis.
It seems that in addition to dopamine, the nervous system wires coming from fat cells and ending in the brain also express melatonin receptors, and melatonin hitting these receptors triggers additional lipolysis. This is actually surprising to me, as when I was supplementing melatonin to help cope with shift work I could swear I was gaining bodyfat. I will admit though at the time that I was still eating a junk food diet, that was very insulinogenic.
Insulin really is the daddy you know.
I think this also explains why reduced sleep is linked to obesity, less melatonin reduces lipolysis, giving the chance for fat cells to increase in size the next day when you eat normally. Could it be the same principle for why dopamine blocking drugs cause weight gain? Its not that blocking dopamine causes fat storage, but rather, it greatly inihibits fat break down. The paper also mentions how blocking this nervous system activation causes less lipolsis when fasting.
Monday, 26 March 2012
Peter@Hyperlipid should hopefully be making a much more thorough post on Veech's papers in the future but in the meantime I thought id list here some interesting points and possible implications from his latest paper linked above.
Surprisingly, Veech opens with the observation that the degree of Ketosis that is usually reached on a Ketogenic diet is, at best, "modest". He goes on to further state that almost complete avoidance of all carbohydrate calories is needed to get insulin sufficiently low enough to keep adipose tissue lipolysis high enough to fuel increased ketogenesis levels.
Recall that, the liver will in general produce ketones as fast as it can, and the only thing that stops the liver doing this is insulin and the availability of free fatty acids coming from lipolysis from the adipose tissue. Also recall, that ketones have a negative feedback loop to help control thier production rate, since adipocytes possess receptor HM74A that is suppose to bind beta hydroxybutyrate and reduce lipolysis. This same receptor also binds nicotinic acid, and is the reason that a niacin shot reduces lipolysis, at-least in the short-term.
Sunday, 25 March 2012
Human fatty acid synthesis is stimulated by a eucaloric low fat, high carbohydrate diet.
Whats up with these people thinking they can eat endless carbs and not gain body-fat? Because De novo lipogenesis is a myth? Better take a look above.
This study shows that exercise intensity, and not duration and/or total energy expenditure can upregulate something called Peroxisomal proliferator-activated receptor gamma co-activator-1 alpha ( PGC-1α ).
There reason intensity is important because of the lactate threshold. Once this threshold is breached, your body is like "Okay damn were exhausted, time to make new mitochondria to cope with all this lactate"
- It reduces hyperglycemia in diabetic rats and humans.
- The results indicate that fructose enhances hepatic glucose uptake and glycogen synthesis and storage via activation of hepatic glucokinase and glycogen synthase, respectively.
Whoa, was this study sponsered by the Honey industry? There has been much fructose bashing over the recent years, so they have to be afraid. Still, I never had a problem with Honey in the same way I have with starch, I do find honey kind of a more-ish food though. Still, I think its fine in small amounts as a sweetner.
Saturday, 24 March 2012
Heres what I used.....
From left to right we have, Sainsburys organic double cream, Kerrygold butter, Cocoa, Ground Almond, Nestle full cream milk powder ( only use full cream ), stevia
Ingredients:- ( this batch will contain only about 15g carbs, coming from low GI sources )
40g double cream
3 tablespoons cocoa powder
2 tablespoons milk power
40g ground almond
25g stevia ( adjust this depending on how sweet you want it)
Step 1 - sieve the cocoa, milk powder, almond, and stevia into a large bowl
Step 2 - melt the butter and gently heat it with the cream until the butter is melted.
Step 4 - after butter is melted and mixed with cream ( on only gentle heat remember ), pour into mixture and mix away!
Step 5 - Mix throughly, then put into a dish, and put it in the fridge for a few hours! Then done!
Im not going to put up the after pictures because in this particular batch I used too much cream and it came out looking like something youd do in the rest room, lol.
Anyway, since cream and butter dont properly solidfy when cooled you will find it comes out soft and is more like fudge than block chocolate. You can use coconut oil to replace any portion of the cream and butter but it will impart a strong coconut flavor to it.
You can also vary the amount of cream and butter used to depending on how soft/squishy you want it. Another good option is to add chopped hazelnuts.
Obesity Warning! This is a HIGH REWARD FOOD and is ADDICTIVE. rrraarrgggggghhhhhh!
UPDATE:- ok I decided what the hell, put up the after pictures, NO LAUGHING PLEASE LAWL.
If I zap all the catecholamine receptors in your fat cells, and then starve you, you wont lose ANY body fat. It doesnt matter about calories in calories out.
You see, most of the fat in fat cells is locked away inside the central lipid droplet, like car's in a car park. They dont just "flow" naturally outside when needed anymore than car's roll out of car park's if all the roads outside are empty.
For car's to get out of car park's, you need people to drive them out, on purpose. Deliberately. In the same way, you get fatty acids out of the central lipid droplet so they can be oxidised mainly by catecholamine binding.
Perilipin, the main protein that surrounds lipid droplets, is activated by catecholamine binding, it then lets fats out of the central lipid droplet so they can be broken down by hormone sensitive lipase and other enzymes.
Perilipin is hyperphosphorylated by PKA following β-adrenergic receptor activation. Phosphorylated perilipin changes conformation, exposing the stored lipids to hormone-sensitive lipase-mediated lipolysis. Although PKA also phosphorylates hormone-sensitive lipase, which can increase its activity, the more than 50-fold increase in fat mobilization (triggered by epinephrine) is primarily due to perilipin phosphorylation
Thursday, 22 March 2012
Wednesday, 21 March 2012
First, what is a lipid droplet?
Its basically a car-park for triglyceride inside cells, its classified as an organelle, and its where all the triglyceride goes for long term storage. The lipid droplet is surrounded by a phospholipid monolayer along with protein linking chains, one type of the proteins is called fsp27
What does Fat-specific protein 27 do?
Well it would appear that research is ongoing at the moment, a pubmed search of fsp27 yields only a small number of reports. But what we have so far seems to indicate that it is involved in the merging of smaller lipid droplets into larger ones. If you look at this study you can see pictures of fat cells with both small and large amounts of fsp27. In the cells with alot of fsp27, the lipid droplets are enlarged, and merged. The study also reports increased mitochondria in cells that have relatively little fp27, and they have many many small lipid droplets.
I should point out though that the form of intermittent fasting in the study mentioned above was an extreme version, 3 days on 3 days off. As im aware, that is a far cry from what many people practice normally.
Anyway, another study was able to show that fsp27 knockout causes fragmentation of lipid droplets, resulting in increased energy expenditure. They have some colorful cartons to show how it works.
Tuesday, 20 March 2012
Saturday, 17 March 2012
We already saw from here that confidence is very seductive. But the looming question is, why?
Well, I reckon its because of this, as I posted on before, Ambiguity Aversion: we don't mind risk but we hate uncertainty.
Confidence is nothing more than the communication of certainty. And we love certainty, as demonstrated by the age old test, what do you want, a garaunteed £500, or, I flip a coin, if you win you the flip you get £1000, if you lose the flip, you get NOTHING. ( most people chose the garaunteed £500 )
A bird in hand is worth two in the bush.
blah blah blah.
Sunday, 11 March 2012
ChREBP is basically gene expression induced by carbohydrate consumption, Lucas Tufar has blogged about it here, I say destiny in the title because nuclear receptor binding is inevitable. ( aslong as your not some kind of freakish mutant ) Nuclear receptor binding is the definition of gene expression, and ChREBP is involved right at the nuclear level, right next to your DNA.
- ChREBP activates downstream target genes, including fatty acid synthase
- leading to lipid accumulation, increased oxidative stress, reduced insulin gene transcription/secretion
- and enhanced apoptosis ( wweeeeeeee, self-destructing beta cells is good for your health )
- beta cell-specific Chrebp overexpression is sufficient to phenocopy glucotoxicity
All of this is irrelevant ofcourse because we all know the problem is too much dietary fat.
Friday, 9 March 2012
Fuel Metabolism in Starvation
Annual Review of Nutrition
Vol. 26: 1-22 (Volume publication date August 2006)
First published online as a Review in Advance on May 9, 2006
- studying carbohydrate metabolism using C14 in liver slices from normal and alloxan diabetic rats. Fructose uptake was similar; however, labeled glucose conversion into glycogen, fat, and CO2 were all diminished in the diabetic. Insulin therapy corrected the deficiency.
- In contrast to muscle, glucose permeated the liver cell wall equally in normal and diabetic patients
- Many small points were clarified regarding adipose tissue, such as the release of free glycerol with the fatty acids mobilized during fasting or epinephrine stimulation
- But all of these studies suggested that the role of insulin in fasting is very important, perhaps as important as its role in the fed state.
- We also fasted two type 2 diabetics, who differed from the normals by better nitrogen conservation. They were slightly more efficient, in keeping with the concept of James Neel (at Michigan) that type 2 diabetes may have been an evolutionary selective advantage in a starving population.
- Three very intelligent obese subjects were selected for a five- to six-week starvation study (Figures 1 and 2). Urinary nitrogen excretion fell to 4–5 grams/day, and catheterization of the jugular, as we expected, showed some two thirds of brain fuel consumption to be D-ß-hydroxybutyrate and acetoacetate, markedly diminishing the need for muscle proteolysis to provide gluconeogenic precursors
- About two fifths of fatty acid metabolism in the whole body is via hepatic ketogenesis, some 100 to 150 grams/day. Yet there is still significant brain metabolism of glucose
- Total splanchnic glucose production in several weeks' starvation amounts to approximately 80 grams daily. About 10–11 grams/day come from glucose synthesis from ketone bodies, 35–40 grams from recycled lactate and pyruvate, 20 grams from fat-derived glycerol, and the remaining 15–20 grams from protein-derived amino acids, mainly alanine
- The kidneys in starvation produce about two fifths of new glucose.
- Next, I turn to the question of what controls hepatic glucose production. It appears simply to be the rate of release of alanine from muscle as reflected by its blood concentration
- Elevated levels of ß-hydroxybutyrate inhibit adipose release of free fatty acids (73, 81), but insulin is necessary for this effect.
- However, caloric homeostasis in a 70-kg man on protein alone is incompatible with life since the maximum rate of urea synthesis is insufficient to provide even basal calories, about 1000–1300 Kcal/day, or 250–325 grams of protein
- Veech and colleagues discovered that administering ß-hydroxybutyrate to the perfused rat heart in place of glucose increased work output but decreased oxygen consumption
- Essentially, any cell challenged by low oxygen availability or by a toxin interfering with mitochondrial function should benefit by utilizing ß-hydroxybutyrate in preference to any other substrate, including glucose, lactate, pyruvate, or fatty acids. In a very simple experiment, mice given ß-hydroxybutyrate exposed to 4% oxygen survived longer.
Born to run; the story of the PEPCK-Cmus mouse
It has some surprising implications, and ties in with my previous post. This study would seem to suggest that it is NOT calorie restriction that promotes longevity, but rather it is having a high number of mitochondria and running your metabolism on fat!
These studies focused mainly on the potential role of PEPCK-C in the generation of alanine, which occurs during fasting in skeletal muscleAlanine is the main amino acid ejected from muscle during fasting to fuel for glucose creation to support the brain.
biochemical analysis of the skeletal muscle indicated high levels of triglyceride in that tissue. In fact, the concentration of triglyceride in the skeletal muscle of the PEPCK-Cmus mice was directly proportional to the activity of PEPCK-C in the muscle, suggesting the importance of glyceroneogenesis in the tissue.Fat burning metabolism folks.
Skeletal muscle triglyceride is clearly the major fuel driving the hyperactivity in the PEPCK-Cmus mice; they have many more mitochondria in their skeletal muscle than found in the muscle of controls, supporting the enhanced rates of fatty acid metabolism noted in the mice.What did I just say?
After weaning, the PEPCK-Cmus mice eat 60% more than control littermates but weigh almost half as much.So I guess that means thier running a fast metabolsim and should live relatively short lives, right?
A second surprising result was the apparent extend longevity of the PEPCK-Cmus mice; they lived almost two years longer than the controls and had normal litters of pups at 30 to 35 months of age (most mice stop being reproductively active at 12 to 18 months).Whoops, guess that theory is out the window now.
levels of hormones and cytokines in the blood of the PEPCK-Cmus mice and noted very low levels of insulin, leptin and MCP-1 as compared to control animalsLow insulin. They say in the study that the low leptin is because they have very low amounts of white fat mass.
We suspect that the major factor responsible for the longevity of the PEPCK-Cmus mice is the very low concentration of insulin in the blood of the mice that is maintained over their lifetime of hyperactivity.Yeh so what was I saying, low insulin.
Anyway, the only question mark in this study is, what is driving the mice to be excessively active? Is it the fact they have a large number of mitochondria? Or is the fact that overexpression of PEPCK-C results in increased cleareance of citric acid cycle waste products?
Tuesday, 6 March 2012
Paddles are attached to the specified area of the body and a low class laser is used to penetrate just under the skin to break down the underlying fat cells. When the laser hits the fat cells, pores form on the cells and they release water, glycerol and fatty acids. The fat cells reduce in size.The lymphatic system then removes the glycerol and fatty acids through the venous system where they are processed in the same way as fatty foods that are digested. It is therefore crucial that clients exercise after treatment to metabolise the fatty acids.The treatment does not affect any of the surrounding structures such as the skin, blood vessels or nerves.
Monday, 5 March 2012
Enhanced glycogen metabolism in adipose tissue decreases triglyceride mobilization.
Stranger in a strange land: roles of glycogen turnover in adipose tissue metabolism.
Both these studies are free full text, going to read over them and update this post when ive made my own conclusions.
Sunday, 4 March 2012
Sustained activation of PPARα by endogenous ligands increases hepatic fatty acid oxidation and prevents obesity in ob/ob mice.
PPARα is nothing other than simply a certain receptor sported on the nucleus of mainly your liver cells. And it binds fatty acids. I havent so far been able to find a comprehensive list of ligands but PPARα is reported to be responsible for the fasting response.
PPARα activation also reverses fatty liver. yay!
In the study above the researchers manipulated some enzyme called Peroxisomal acyl-coenzyme A oxidase 1, basically turning it off, such that PPARα was excessively activated, the result was a lean rodent. ( even though this rodent is genetically predisposed to be fat )
However it seems there was a price to pay, all the extra fat burning in the liver resulted in oxidative stress overload and liver cancer.