Do leptin levels/sensitivity fall ONLY in relation to BF% ...

[SteelWeaver]

... or does the length of the diet affect things?

Say one diets at a SMALL deficit for a long time, or diets at a LARGER deficit for a shorter time, (both with refeeds) resulting in the same bf%, in which case will leptin drop further?

 

[SteelWeaver]

OK, hang on. I KNOW the length of the diet affects things, but I'm wondering what affects leptin more - the deficit or the length of time dieting.

Alright - edited to include results of search on PubMed: for anyone wondering why a smaller caloric deficit is better than a BIG one:



Clinical implications of leptin and its potential humoral regulators in long-term
low-calorie diet therapy for obese humans.

Miyawaki T, Masuzaki H, Ogawa Y, Hosoda K, Nishimura H, Azuma N, Sugawara A,
Masuda I, Murata M, Matsuo T, Hayashi T, Inoue G, Yoshimasa Y, Nakao K.

Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine,
Kyoto, Japan.

OBJECTIVE: To address the clinical implications of leptin and to re-examine the relationship
between leptin and its potential humoral regulators such as insulin, nonesterified fatty acids (NEFA)
and triiodothyronine (T3) in low-calorie diet (LCD) for obese humans. DESIGN: Longitudinal study.
SETTING: University and foundation hospitals. SUBJECTS: Ten obese men and 10 premenopausal
obese women. INTERVENTIONS: Five men and five women took 800 kcal/day LCD and another five
men and five women took 1400 kcal/day balanced deficit diet (BDD) during 4 weeks. RESULTS:
Plasma leptin levels in the LCD group decreased more markedly (46.2+/-14.6 to 13.2+/-3.6 ng/ml)
than that expected for the decrement in percentage fat (39.0+/-1.7 to 35.9+/-1.7%) and body mass
index (BMI; 35.4+/-2.4 to 33.1+/-2.2 kg/m(2)), while that in the BDD group did not decrease
significantly (14.9+/-3.5 to 13.4+/-2.8 ng/ml). The ratio of the decrease in leptin levels to that of
BMI during the first week was significantly greater than that during the following 3 weeks
(39.5+/-2.7 vs 29.3+/-2.1%, P=0.017). The plasma insulin and T3 levels also fell substantially in the
first week and continued to decrease during the entire course. Plasma leptin levels measured
weekly in each subject were correlated well with insulin (r=0.586, P=0.0003) and T3 (r=0.785,
P=0.0004). Multiple regression analyses after adjustment for the time course and BMI revealed that
serum levels of T3 were independently correlated with plasma leptin levels (r=0.928, P<0.0001). The
plasma NEFA level was markedly elevated during the first 2 weeks and decreased thereafter.
CONCLUSIONS: A rapid fall in leptin during the first week of LCD, coordinated by insulin, T3 and
NEFA, should be beneficial for responding to decreased energy intake. Inversely, in view of the
powerful effect of leptin on energy dissipation, the present findings suggest the potential usefulness
of leptin in combination with caloric restriction for the treatment of obesity. SPONSORSHIP: The
Ministry of Education, Culture, Sports, Science and Technology of Japan and the Ministry of
Health, Labour and Welfare of Japan. doi:10.1038/sj.ejcn.1601363

 

[MS]

At first I thought there was a typo in that abstract......for the LCD group they have leptin dropping FROM 46.2 to 13.2 ng/ml, but in the BDD group the levels go FROM 14.9 to 13.4 ng/ml...................On closer examination of all of their data, I see thay had some serious problems with allocation to the two study groups. The people that ended up in the LCD study ALL had very much higher initial leptin levels compared to the folks that ended up in the BDD group. In fact it appears that the lowest initial leptin levels in the LCD group was still higher than the highest initial leptin in the BDD group. Very, very bad science IMHO. Aside from that, the authors also noted that everyone in the LCD group was basically in ketosis by the end of the first week whereas no one in the BDD group had any measureable ketones at any stage of their diets.

So all we can conclude from THAT study is that a ketogenic diet is harder on leptin levels, T3 etc..., (tell us something we don't already know!) and that folks with higher initial leptin levels (ie leptin resistance in my opinion) may experience a greater diet induced decrease in leptin levels (and no doubt reduced leptin resistance) than people with more modest initial leptin levels.

It is well known that people coming off calorie restricted ketogenic diets often experience a worse fat rebound than people coming off of non-keto diets. So this all makes sense, but doesn't really answer your original question. We also know that people coming off of ANY severely restricted diet are at worse risk for rapid rebound fat gain than people that go on more modest and gradual weight loss plans. So I would suspect that slower is better than rapid weight loss in terms of leptin homeostasis, but as far as I know there are no studies that can directly answer that question. The common mantra is that CRASH diets don't work, but more and more it is becoming recognized that DIETS don't work. It may just be that if you take it off more slowly, you'll put it on again more slowly, but you'll still put it on

 

[JJFigure]

That's a question for Par Deus...maybe he would have some insight.

 

[MS]

Maybe I wasn't clear in my answer. Without a doubt, leptin levels fall faster and further with a short term severe calorie restriction diet compared to a less dramatic, longer duration diet. However over the long term, leptin reduction is mostly correlated with the overall loss of bodyfat rather than how you achieved that loss of bodyfat. At least this is true for obese people, but in this population the reduction of leptin may likely just be a 'normalization' of leptin sensitivity which is often diminished in obese people. Loss of subcutaneous fat may also reduce leptin levels more dramtically that loss of visceral fat, and may explain part of the rapid drop in leptin levels seen with extreme calorie restriction (since this tends to be more from subQ depots in the initial stages of very low cal diets in women).

Long term changes in leptin concentration during weight loss track with changes in body fat. However, neither baseline concentrations nor initial (rapid) changes in leptin predict success at weight loss or maintenance over the long term.

 

[SteelWeaver]

Mmm, I didn't notice that - for some reason my eyes fixate more easily on words than numbers Gotta work on that. Anyway, I guess I'm just wondering how come my energy levels are still fairly decent, compared to last time, particularly since my calories are lower.

There's a whole lot of very interesting stuff about leptin at PubMed - been meaning to get over there -I'm glad I did - it's really worth the time.

MS, here's a question: how do they check leptin levels anyway? Like, say one had access to a lab, could one monitor one's own levels, just for interest's sake?

And how do they test leptin sensitivity??? Since this seems to really be the main issue in humans, more than levels.

 

[MS]

Leptin is commonly measured using an RIA (radioimmunoassay). There are commercial kits available, but you would need to be able to obtain your own serum or plasma, have available appropriate plates and plate readers, reagnets, as well as control leptin to standardize your results.

Leptin resistance is not, as yet, something that can be definitievely measured. There are varying degrees of both peripheral and central leptin resistance (and you can have one or both). Some groups use measures such as relative change in leptin to bodyfat, or leptin to BMI ratios, but these are not very helpful. Certainly if someone loses 10% of their bodyfat, but their leptin levels drop by 50%, you have a pretty clear case of pre-diet leptin resistance. From a practical point of view, if you continue to gain fat and you also have high leptin levels, it's a pretty high certainty that you have some resistance to leptin's signal! Insulin resistance and leptin resistance are also pretty highly correlated, so any measure of insulin resistance can be taken as leptin resistance too, especially if you are overweight or female.

 

[SteelWeaver]

" Leptin is commonly measured using an RIA (radioimmunoassay). There are commercial kits available, but you would need to be able to obtain your own serum or plasma, have available
appropriate plates and plate readers, reagnets, as well as control leptin to standardize your
results."

Are these things available in the typical university lab? Do they let students stroll in and use them? A control could simply be my own when not on diet, couldn't it?

(ha ha - big plans for next year ...)

 

[MS]

"Are these things available in the typical university lab?"

It would depend entirely on the university. Unless you were in a lab that specifically worked on human leptin, the chances are not very good that you could do this yourself. You would also still need human leptin of a known quantity and quality for comparison....this is because of the sad reality (especially in University settings) that experimental results can vary tremendously from one day to the next, and even on the same day between experiments. Without a control, you have no way of knowing what your results mean. You would also need labelled human leptin antibodies. In general you need negative controls (absolutely no leptin), and a dilution series of positive controls containing a range of knows concentrations of leptin. You can buy premade diagnostic kits, but these tend to be expensive by university standards and are often only used in a diagnostic/commercial lab where they can pass the high cost of the test on to the consumer.

In addition to all of this, there is still no easy way to measure central (ie CNS/brain) levels of leptin and it's receptors. The above test will only tell you what the plasma levels are and there is reason to believe that a lot of the symptoms of leptin resistance may be due to changes in CNS uptake of leptin from theplasma, as well as changes in receptor numbers and isoforms (much the same as insulin resistance is in part mediated by reduced cell surface expression of GLUT4). It's not JUST high peripheral leptin levels that you need to look at, though they do tell part of the story.

 

[SteelWeaver]

Thank you!

Darn! Well - I'm certainly going to go poking my nose in the labs next year and asking LOTS of questions

In the meantime, I suppose all I'm left with is experimental dietary and training manipulation on myself and my family (and anyone else I can convince to pay close attention to what they're feeling on a daily/half-daily basis). I already have a fairly good log of what goes on with me on this particular diet. I need to work on what happens when I tweak it, though.

Anyway, my reason for starting this thread turned around and slapped me in the face yesterday It all came back, like a creeping scurvy, a horrible recurring nightmare - the leaden legs, the tripping, dragging feet, the difficulty getting up from my futon, the RUDE and unpleasant grumpiness ...

May as well settle into the routine - doesn't get any better from here on in But by golly I'm gonna ripped if all goes smoothly