You can always find a reason why a trade was "wrong"

It took a while to sink in but what I have learnt about trading is that backtesting is very naive, and whenever you make a loosing trade, you can ALWAYS find a reason why it went wrong by backtesting.

The biggest dilemma is that of support/resistance vs the trend. If you make a losing trade on S/R, then the guru will always say "you went against the trend",

If you make a losing trade going with the trend, the guru will just say you bought/sold into S/R!

Having said that, trading on S/R is really the only way to trade I feel, you need to go into profit asap and have a very very tight stop, for when you enter a trade with the trend but go into negative territory your faced with the hard decision, do you hold the trade and wait for price to come back and put you into profit? Or do you exit the trade NOW and take the loss, only to watch price come back to your level and go your way later?

Trying to make an active decision here always puts you at a loss. I nearly always made the "wrong" decision, exiting a losing position too early , or hanging onto trades that went hundreds of pips against me since last time it "came back".

You have to trade like a robot, and be very mechanical with your system. Never use intuition, just go with price and what the chart is saying.

This also brings me to the subject of following so called "experts" and analysts through various websites, countless predictions are made which almost always turn out to be wrong. Yet I still find myself looking at their opinions and it always sways my own judgement.

if guru X says the market is going to fall, then that affects my own opinion and affects how I trade. Indeed, following the news and listening to others is probably the worst thing I am doing, its just "noise", only the price and chart is the "signal".

Trading is the hardest thing I have ever done, its no surprise the vast majority lose their money, whenever you enter a trade, you always have at least a 50% chance of being right, but emotion is so powerful it always make you trade too defensively.

One thing that is clearly so deeply rooted into human psychology is the urge to always gamble the loser and accept the small winner.

When faced with the proposition of definitely accepting a small loss, or taking a gamble between losing nothing or accepting an even bigger loss, we ALWAYS gamble.

K(ATP) channels and fat cell multiplication

Involvement of ATP-sensitive potassium channels in proliferation and differentiation of rat preadipocytes.

These results suggest that when ATP-sensitive potassium channel expression decreases, preadipocyte proliferation is promoted, but when the expression of the channels increases, preadipocyte proliferation is inhibited.

It is to be confirmed whether the development of obesity has relation to excessive inhibition of ATP-sensitive potassium channels in preadipocytes or not.

hhhmmmm, inhibition of K_ATP channels, where have we seen that before? Oh yeh, here, this is what they say.....

"increased intracellular glucose, resulted from hyperglycemia, increases cytosolic ATP through glucose metabolism. This leads to closure of ATP-sensitive potassium ion channels (K_ATP channels) "

So how do we get increased intracellular glucose?, Yup, INSULIN.

No wonder the K_ATP knockout mice cannot get fat, they have no K_ATP channels to close in the first place! And so the downstream signalling cascade from the closure of the K_ATP never happens!

GABA also plays a role in body-fat regulation

GABAergic signaling by AgRP neurons prevents anorexia via a melanocortin-independent mechanism.

"AgRP neurons, also co-release neuropeptide Y (NPY) and γ-aminobutyric acid (GABA) to promote feeding and inhibit metabolism"

So the AgRP neurons also secret NPY and GABA, and this helps make you fat by suppressing the action of the POMC neurons, infact AgRP blocks the melanocortin 4 receptors, which is VERY bad news because blocking those receptors is a strong factor for bodyfat gain.

According to the abstract, removing the AgRP neurons essentially makes you stop eating and you die of starvation. So clearly the AgRP neurons are what makes you "hungry"

However, even if you delete the AgRP neurons, feeding behaviour can be restored by the administration of bretazenil, which is a GABA agonist. Interesting! So GABA receptor binding in the parabrachial nucleus plays a massive part in food intake.

Melanocortin 4 Receptor and Roux-en-Y Surgery

I rememberd reading on Stephen Guyenet's blog here about how weight loss surgery has no effect on those poor people with Melanocortin 4 receptor ( MC4R ) mutations, the link that Stephen gives in his blog is to a study that that looked at gastric banding surgery, which is actually significantly different from Roux-en-Y surgery.

In Roux-en-Y surgery, the ileum l-cell rich part of the intestine is moved right next to the entrance of the new stomach, but also, bile acids secreted from the gall bladder are given direct access to the rest of the ileum, which seems to cause hypersecretion of GLP-1 and results in intense stimulation of the POMC neurons.

I recently came across this study here that suggests that in actuality, even those people with MC4R receptor mutations may benefit from surgery aslong as it is Roux-en-Y.

I think this could be one of the strongest arguments yet for the power that incretins and bile acids play in bodyfat balance. Is it so powerful that it can even go someway as to help alleviate some the dreaded MC4R mutation effect of morbid obesity?

Neuropeptide Y - Insight into what it does

Moderate long-term modulation of neuropeptide y in hypothalamic arcuate nucleus induces energy balance alterations in adult rats.

Administration of leptin or insulin suppresses the expression of NPY (about 0.5 to 1.5-fold decrease of ARC NPY levels) and reduces food intake in lean rats and in rodent models with elevated NPY expression, such as ob/ob mice, fasted rats or diabetic rats.

NPY production is stimulated by negative energy conditions, such that food deprivation induces a potent up-regulation in the expression of NPY and AGRP (5–10 fold increase as compared to basal).

Furthermore, NPY levels return to initial values within 6 to 24 hours after re-feeding. (well that is good to know,)

In addition, some studies also report elevated levels of hypothalamic NPY (30%, in average) in diet-induced obese mice (DIO). However, other studies show a compensatory down-regulation of NPY expression in the ARC and immunoreactivity in the PVN in rats fed with high-fat diet for variable periods of time which was related to the inhibitor effect of elevated leptin concentrations.

Overall this study shows that a forced increase in basal NPY leads to extreme over-eating and extreme fat gain.

However

Reducing NPY strangely leads to normal feeding under basal circumstances, BUT, the mice did not increase thier food intake after a period of calorie restriction!

This suggests that the upregulation of NPY after calorie restriction is an essential survival mechanism. This is direct evidence that your body attempts to maintain a "bodyfat set-point", atleast with regards to under-feeding and forced adipose mass depletion.

Leucine deprivation decreases fat cell volume

Unfortunately these studies did not show a reduction in fat cell number by apoptosis but they did show a marked reduction in fat cell volume, generally speaking it is fat cell number reductions that we want, but still these studies are interesting nonetheless.

Leucine deprivation decreases fat mass by stimulation of lipolysis in white adipose tissue and upregulation of uncoupling protein 1 (UCP1) in brown adipose tissue.

As we recently reported, mice maintained on a leucine-deficient diet for 7 days experienced a dramatic reduction in abdominal fat mass (9).

In our current study, we observed increases in lipolysis and expression of β-oxidation genes and decreases in expression of lipogenic genes and activity of fatty acid synthase (FAS) in WAT,

In addition, we observed for the first time that leucine deprivation increases expression of uncoupling protein (UCP)-1 in brown adipose tissue (BAT), suggesting increased thermogenesis.

The rapid fat loss induced by leucine deprivation suggested a possible increase in energy expenditure.

Serum free fatty acid (FFA) and glycerol levels were much lower in leucine-deprived mice than in pair-fed and control diet–fed groups

Consistent with these findings, no apoptosis was detected by Tdt-mediated dUTP nick end labeling (TUNEL) staining in mice maintained on a leucine-deficient diet

the results of the present study show that leucine deprivation significantly reduces body weight and abdominal adipose mass without affecting proportion of lean body mass

Mice maintained on a leucine-deficient diet, however, reduced their food intake by 15%. These results are consistent with previous studies showing that mice consume less food when provided with a diet deficient in essential amino acids

Fat mobilization in response to increased energy requirements is normally mediated via increased activities of the sympathetic nerve system

Leucine Deprivation Stimulates Fat Loss via Increasing CRH Expression in The Hypothalamus and Activating The Sympathetic Nervous System.

leucine deprivation stimulates fat loss by increasing expression of corticotrophin-releasing hormone in the hypothalamus

the effect of leucine deprivation on fat loss is mediated by activation of the sympathetic nervous system.

Cutting calories to loose weight changes your brain

Obese reversal by a chronic energy restricted diet leaves an increased Arc NPY/AgRP, but no alteration in POMC/CART, mRNA expression in diet-induced obese mice.

"Arc neuropeptide Y (NPY) and agouti-related protein (AgRP) mRNA expression in DIO mice after obesity reversal were significantly higher than DIO mice without obesity reversal (17%, 47%, both p<0.05),"

This means that post obese mice will have lower energy expenditure, increased hunger, and an increased tendency to store fat mass.

"while the Arc pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) mRNA showed no difference."

" Both NPY and AgRP expression in DIO mice were negatively correlated with plasma leptin (R=-0.78, p<0.05; R=-0.72, p<0.05)."

" In conclusion, while chronic energy restriction will lead to weight loss, it can up-regulate hypothalamic orexigenic peptides, which may be an important contributing factor to weight regain after a weight loss program from an energy restricted diet."