The FastDay Forum

Typing out loud as I try to get my head round it.....

http://www.ncbi.nlm.nih.gov/pmc/article ... figure/F1/ shows how wwhite adipose tissue ( WAT ) generates leptin that acts on the brain as does insulin. RThe brain can then affect storage of fat in the WAT via the sympathetic nervous system (SNS).

Insulin increase can act on the brain via the SNS to increase fat storage (lipogenesis) and reduce fat release from storage (lipolysis). This is in addition to insulin acting directly on the fat cells.

Leptin works the other way, extra leptin acting on the brain decreases fat storage and increases fat release.

Leptin decificient mice / humans or those with the leptin receptor knocked out genetically get very obese, as the leptin being released from their growing fat cells doesn't influence them to eat less or reduce fat storage. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC150795/ also see ob/ob mouse.

The bit I'm struggling with is that obese people tend to have high leptin, because they have a lot of fat cells releasing it. However the leptin doesn't do what it should - it looks like "leptin resistance". On the TV show Embarrassing Fat Bodies the slender Dr Dawn had low levels of leptin but her obese friend had high levels.

Other reading material
http://ajpendo.physiology.org/content/277/5/E855.long - "Leptin response to carbohydrate or fat meal and association with subsequent satiety and energy intake"

http://www.ncbi.nlm.nih.gov/pubmed/9084 ... t=Abstract talks of leptin being proportional to carbohydrate intake and falling during diet as less CHO intake.

[carorees]

See also the paper I summarised today on why we put weight on again after losing it. It says that leptin levels are low in people who have lost weight which prompts overeating.

I also saw a paper saying that the leptin response to food is impaired in obese people.

It's not easy to get your head around because there are at least 50 molecules produced in the body that affect appetite, adiposity and energy use. And they all interact! I'm not sure I'll ever be able to understand it!

Fascinating but confusing... So leptin and insulin work in opposition, maybe in the overweight the insulin dominates and in the more svelte the leptin dominates?

[carorees]

Overweight is associated with high insulin levels due to insulin resistance so yes to some extent, but it's complicated! I think it's more that leptin and ghrelin work in opposition.

Mark with his daily apple has written well on leptin too.

http://www.marksdailyapple.com/leptin/#axzz2JMuIU2uh

My quest to find the answer on what makes us fat just gets more and moe complex. All interesting stuff though. Thanks for posting the above Phil.

Fascinating but confusing... So leptin and insulin work in opposition, maybe in the overweight the insulin dominates and in the more svelte the leptin dominates?

Leptin and Insulin work in opposite ways, yes - insulin drives fat storage and leptin drives release / inhibits storage.

However the svelte don't have the fat cells producing the leptin (Dr Dawn of embarrassing bodies is <60 kg and has low leptin).

... Thanks anyway Phil!

Mark with his daily apple has written well on leptin too.

http://www.marksdailyapple.com/leptin/#axzz2JMuIU2uh

thanks, he has a follow-on at http://www.marksdailyapple.com/further- ... z2JRsa2PZr

Seems only the lean need worry about carb refeeds, as there'll be enough leptin around in the obese.

Hi PhilT ,I did the 'Leptin reset' as per Jack Kruise.I did it for eight weeks, it was an interesting experience and I'll let ya know soon if it worked.
Barbara

http://www.ncbi.nlm.nih.gov/pubmed/20461357 is an overfeeding study where the (overweight) participants were fattened up for 28 days and "Circulating leptin increased significantly with weight gain and to a greater extent in FH+ than in FH− participants at 28 days (Fig. 2b), consistent with the greater weight gain in the former group. The increases in circulating leptin concentration at days 3 and 28 correlated with weight gains at these time points"

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3329711/ reduced weight by 10% in young overweight subjects and observed that "Consistent with the loss of fat mass, there was a significant decrease in serum leptin concentrations in both calorie reduction and calorie reduction plus exercise groups".

http://www.ncbi.nlm.nih.gov/pubmed/12809176 did a 3 week intervention on morbidly obese subjects giving a 7% reduction in fat mass and observed leptin levels fall, however the subsequent rate of weight loss was inversely related to the baseline leptin levels. In other words subjects who entered the trial with higher leptin levels (absolute and per kg fat mass) were less successful at losing weight after the 3 week intervention.

http://www.ncbi.nlm.nih.gov/pubmed/11285459 is interesting, a steroid drug dexamethasone doubled serum leptin and insulin level in a one-off test.

After 8 weeks on a 1000 calorie/day deficit the leptin level reduction was significant, from 25 to 16 ng/ml http://www.scielo.br/img/fbpe/bjmbr/v34 ... 742t03.htm
At baseline the obese group had substantially higher levels of leptin (22.9 ± 12.3 vs 5.7 ± 3.2 ng/ml) and once again "Baseline plasma leptin levels correlated highly with the percentage of fat (r = 0.88, P<0.0001)"

So fat people have more leptin, in proportion to their fat mass. Dieting reduces leptin faster than fat mass reduces but it is still well above the baseline for healthy people.

Wow Phil! That must be a record for number of links in a post. Lots of reading matter, I confess I haven't been able to study it all yet...

Would it be fair to say that leptin is what triggers the 'hunger feeling' in a 'good' way? People who are thin should feel hungry (at least in evolutionary terms) and it is the body's way of telling them to get more food. People who are overweight don't get this natural hunger feeling, so you might expect them to stop eating, but instead it tends to get replaced by alternative triggers. When an overweight person starts losing weight then on top of those alternative triggers the leptin effect starts to come in more strongly too, so they feel 'doubly' hungry?

One part of the solution is to learn to love hunger, or at least learn to live with temporary hunger and feel it as a good thing. Which is what 5:2 seems to be achieving for so many...

When an overweight person starts losing weight then on top of those alternative triggers the leptin effect starts to come in more strongly too, so they feel 'doubly' hungry?

sounds plausible, yes. Adding a hungry feeling to a compulsive / habitual eater isn't going to help them lose weight.

http://jama.jamanetwork.com/article.asp ... eid=192037

"A dose-response relationship with weight and fat loss was observed with subcutaneous recombinant leptin injections in both lean and obese subjects. Based on this study, administration of exogenous leptin appears to induce weight loss in some obese subjects with elevated endogenous serum leptin concentrations. Additional research into the potential role for leptin and related hormones in the treatment of human obesity is warranted."

http://ajpregu.physiology.org/content/301/5/R1259.long

"Maintenance of a 10% or greater reduced body weight results in decreases in the energy cost of low levels of physical activity beyond those attributable to the altered body weight. These changes in nonresting energy expenditure are due mainly to increased skeletal muscle work efficiency following weight loss and are reversed by the administration of the adipocyte-derived hormone leptin."

[carorees]

I found some more interesting facts about leptin in a Medscape review: http://www.medscape.com/viewarticle/725342_1 (I think you have to register to see it, but registering is worthwhile as they have some good papers)

Points of interest:

Ghrelin and leptin, putative controllers of human appetite, have no effect on human meal-to-meal appetite but respond to variations in energy availability.

So fasting on one day does not necessarily result in increased appetite the next (as we have observed)

Nonhomeostatic characteristics of appetite and spontaneous activity stem from inhibition by leptin and ghrelin of brain reward circuit that is responsive to energy deficit, but refractory in obesity, and from the operation of a meal-timing circadian clock.

As PhilT discovered, in obesity leptin is not working right.

A sustained inhibitory influence over feeding and a stimulatory influence over energy expending processes (presumed to include physical activity) are postulated to operate in the basal meal-to-meal state, under the influence of insulin and leptin. The inhibitory and stimulatory influences are hypothesized to be relaxed when body weight and fat, as well as plasma concentrations of insulin and leptin, decline to allow for restoration of the predeprivation fat level. A more detailed formulation of this homeostatic view is that the gut peptide ghrelin stimulates feeding in response to negative energy balance whereas meal size and energy balance are jointly regulated by the satiating gut hormones cholecystokinin, glucagon-like peptide 1, and peptide YY, and by the adiposity satiety hormones insulin and leptin.

As PhilT said, insulin and leptin work together to control fatness and appetite, but there are further influences below this level.

Human and animal weights level off at vastly different plateaus depending on nonhomeostatic aspects of food presentation and availability or variable opportunities and necessity for physical activity.[27] Perhaps the strongest evidence contradicting the contemporary model of energy regulation is the absence of a dose-dependent increase in hormonal negative feedback on feeding and physical activity with increases in body fatness.[26] Instead, the effectiveness of leptin and insulin to suppress feeding and activate spontaneous physical activity progressively declines with increases in obesity.

However, as well as insulin and leptin there are many other factors driving weight gain/loss and in obesity there is both insulin and leptin resistance.

[in the authors' study]...hunger was insensitive to short-term fluctuations in energy availability caused by exercise or intravenous nutrient infusions. In addition, exercise suppressed hunger and increased perception of fullness (Fig. 2, left), corroborating similar reports by others[17] and demonstrating again the insensitivity of human appetite to exercise-induced short-term energy deficit.

So, for us, fasting does not result in an enormous appetite.

appetite and meal-to-meal eating seemed to be controlled by stomach capacity rather than by preceding energy deficit

As we have found, we feel full quickly after fasting, presumably due to a smaller stomach.

Much evidence overwhelmingly fails to support a homeostatic role of physical activity in energy regulation. There is a strong negative relationship between spontaneous physical activity and body fat in both animals and humans (Fig. 5). Obesity in rodents is invariably associated with profound hypoactivity whether induced by high-fat diet feeding,[27] lesions of medial basal hypothalamus,[16] or the absence or inactivation of leptin or its receptors.[22] Morbidly obese humans also are reported to be almost completely inactive.[32] Conversely, maintaining rats on restricted access to food leads to 300%-500% increases in spontaneous running as their weight loss increases. If the experiment is not terminated, rats virtually run themselves to death from energy depletion.[24] This animal model is paralleled by human anorexia nervosa, a condition of suppressed food intake, sustained weight loss, and high motivation for, and involvement in, physical activity.[6] Thus, the prevailing evidence indicates that spontaneous physical activity levels are related to body fat in an inverse and nonhomeostatic fashion.

This is seen in the increased energy levels reported by many people during fasting and which probably contribute to fat loss because this increase in NEAT is not taken account of in people's reporting of their activity levels.

Moderate exercise-associated leptin increases also are noticeable in our study (Fig. 3, right) and coincide with temporary suppression of hunger (Fig. 1). If more definitive support is found for the role of leptin in exercise-induced appetite suppression, this leptin action could serve as evidence for its role in functional linkage of meal eating and behavioral activation, and it could reveal a mechanism through which postmeal restraint over feeding contributes to a reduction in the weight plateau that is observed in exercising animals and humans.

This might contribute to the much greater weight loss seen in Krista Varady's study of ADF with exercise compared with no exercise.

Leptin and insulin also contribute to stability of body weight and body fat levels through their metabolic actions. Insulin resistance develops at high body fat levels and limits further nutrient storage and fat synthesis by blunting antilipolytic and lipogenic insulin actions. In this way, high basal plasma insulin concentrations contribute to maintenance of obese body fat levels. During food restriction and body weight losses, higher sensitivity of adipose and other peripheral tissues to insulin favors glycogen and lipid synthesis and drives the restoration of higher body fat levels.

Presumably this implies that eating high carb foods after a fast would be a bad thing?

The magnitude of a nocturnal rise in leptin concentration is proportional to the nutritional state at the onset of darkness. Nocturnal leptin concentration and presumably its lipolytic action[33] are greater in response to energy surplus and lower after energy depletion.[31] Dawn and dusk nadirs of human hunger (Fig. 6) may reflect circadian transition from higher nocturnal leptin concentrations when lipolysis is increased and behavioral activation blocked to the lower diurnal leptin concentrations when leptin may affect the motivation to locomote in conjunction with meal eating. When humans deliberately truncate the period of nocturnal rest, declines in plasma leptin and increases in plasma ghrelin are associated with increased appetite and presumably greater fat synthesis.[29] However, as levels of obesity rise and tissue resistance to leptin action increases,[26] nocturnal lipolytic effects of leptin would be expected to decline and tend to maintain higher body fat levels.

This gives a possible explanation for why obesity is linked with poor sleep. And it might also indicate that saving all ones calories for the evening meal on a fast day might result in more nocturnal lipolysis and so be slightly more effective than spreading ones calories?

The authors conclude:

Human feeding behavior is thus designed for nonhomeostatic meal-to-meal eating and is influenced by social forces that interfere with optimal operation of the energy regulatory mechanism. Environmental circumstances and the design of controls of eating behavior enhance the motivation for food seeking when energy deprived and after body fat loss but also encourage humans to overeat highly palatable and energy-rich foods when not energy deprived. This suppresses physical activity and engages the hedonic brain circuit, both of which contribute to excess fat synthesis and accumulation. Our currently inadequate understanding of the energy regulatory mechanism limits the opportunity to adjust conditions that would allow optimal operation of feeding behavior and physical activity for maintenance of healthy weight.

Stomach size isn't affected by short term eating patterns, is it ?

http://www.womenfitness.net/stomach_volume.htm