Tuesday, 23 June 2015

Leptin and trying to starve yourself thin

Im rather bored writing posts on why calorie restriction or starving is a retarded way to try and get thin. No matter how much physiological  and endocrine evidence is presented ppl are stuck with this meme infecting their brains ,  ....constantly renewing the idea that eating less can make them thin.

Ive lost the link,  its buried deep in my tweets somewhere ........but I found a study where they attempted to starve an ob/ob mouse, to get it the same weight as normal lean chow fed mice. Not only did they have to restrict it to 50% of what the normal chow mouse ate ( that would be like you as a fatty eating 900 calories a day to be the same weight as a normal lean thin person eating 1800 per day ) , but the ob/ob lost a disproportionately large amount of lean mass, such that when it did get down to the same weight as the normal lean mouse, the ob/ob mouse was still "relatively obese" because its body composition was still 45% fat mass.

Given its body composition ( % of weight as fat mass ) that ppl really want to target, you can see that leptin is absolutely crucial to the mixture. Without sufficient leptin, calorie restriction produces exaggerated loss of lean mass, leaving you still "fatty", even if you lose *weight*.

But how exactly does leptin work?

I need to write a more detailed post with links to studies, which I will do when I have more time, but after looking at the FIRKO study, these mice had extremely high leptin levels despite zero insulin action on adipose tissue. A closer look at the study revealed increased food intake in the FIRKO models on high-fat diet or gold thioglucose injury.

In light of this, it would seem that leptin levels are more a reflection of total food intake rather than insulin action on adipose. We also have the well known fact that leptin levels fall disproportionally more and faster in response to calorie restriction than fat mass declines, and this fall in leptin brakes further fat loss.  This point again supports the idea that leptin levels are ultimately a reflection of total food intake, and less so about total fat mass.

It is my contention that even normal lean thin people "over-eat" , since they could easily survive on 1000 calories per day. But they are in "energy balance" while eating 2000 calories per day. Thats because of something referred to as dietary thermogenesis, an increase in body temperature  and energy expenditure in response to food, which is primarily mediated by leptin.

After food intake , calories are stored in adipose tissue, leptin is secreted in response and finds its way to the brain where it activates POMC and alpha-MSH.

In turn, alpha-MSH acts on brain MC4R's , which increases sympathetic outflow to adipose tissue. The sympathetic nerves innervating adipose tissue discharge norepinephrine and this acts on the beta-adrenoreceptors on the adipocytes. This initiates an energy expenditure program, lipolysis increases and fat oxidation is increased.

Beta-adrenoreceptors seem to be responsible for the "browning" of adipocytes, fat liberated by beta-receptors not only flows around the body but there is some evidence the fat is burned within the adipocyte, generating heat. In this way, the body can easily "burn off" extra calories consumed ( over-eaten ) with an energy wasting heat generating furnace in the adipocyte.

This is why a lean thin person eating 2000 calories per day can stay lean, because the intricate leptin-thermogenesis feedback loop is working properly.

Thermogenesis, thats one of the main things leptin "does".

There is a chink in the armor of leptin though. Its called AgRP.

When you calorie restrict or starve yourself, ghrelin produced from the stomach goes up, this finds its way to the brain and increases gene-expression of AgRP, which is a well known antagonist of MC4R, . With MC4R increasingly blocked, sympathetic discharge of  norepinephrine into adipose tissue is culled reducing thermogenesis and energy wasting. The end result is that more of the food you eat ends up staying stored in adipose as as opposed to being burnt off.

I fully expect this is the "starvation mode" people anecdotally speak off, ...I.E.  .when.... after a period of reduced food intake, food seems to more easily cause fat gain.

So, as you can see, aslong as you have functional ghrelin and AgRP, trying to starve yourself thin is futile, because thermogenesis and dietary thermogenesis will drastically drop and youll just store more of the food you eat instead of burning it.

The additional caveat in obesity

Obese people have an additional problem known as cathecholamine resistance. Basically the beta-receptor signal transduction in the adipocytes of obese people is attenuated, there is less Hormone-sensitive-lipase stimulated lipolysis in response to beta-receptor activation. The cause of this is unknown. Although I expect it might ultimately be due to epigenetic changes in gene expression patterns in the adipocytes. This is one of the things that contributes to my idea of  "dysfunctional" adipose tissue being the root thing that makes obesity persistent.

You can see this phenomenon at work because the average age and triglyceride age half-lives are increased  in overweight people, indicating that the adipose tissue of obese people "retains" triglyceride more efficiently.  See below for study.

Adipocyte triglyceride turnover and lipolysis in lean and overweight subjects.

Adipocyte triglyceride age was markedly increased in overweight  compared with lean subjects with triglyceride T1/2 of 14 and 9 months, respectively. Triglyceride age correlated positively with BMI.

Noradrenaline-, isoprenaline- or dibutyryl cyclic AMP-induced lipolysis was inversely correlated with triglyceride age and BMI.


  1. I was very good at losing weight. Much later I learned about John Keifer's contention that you need an insulin spike about every seven to ten days to reset your hormonal milieu. Otherwise, you just get more and more effective at using whatever calories you are taking in to maintain your current weight. When I thought about it, it seems to fit with what I did, even though I didn't know about him then. I was mostly low carb, but I usually got some ice cream (I tried to get stuff with healthier ingredients) about once a week. It would be in the evening too, which he also thinks is important.

    The other interesting author is Seth Roberts who wrote the Shangri-La diet. Because of him I used to take two tablespoons of walnut oil every morning while wearing a nose-clip. The objective was to get the calories without associating any flavor with it. This also meant making sure it didn't associate with morning coffee or toothpaste. It causes appetite suppression- it doesn't always come on right away, but after a week or two I suddenly found myself full and eating less over all. Still don't know why that might be, but it worked extremely well, especially in conjunction with a low carb diet.

    1. I dismissed Keifer as bro advice for the bodybuilders that wouldn't work for me, but the more I view him on youtube the more I warm to his theory about the reset. The guy knows his stuff or maybe he just convinces me well. No way would I do the junk food, but maybe a night of plain sweet taters kept as boring as possible.

      As for Shangri-La, so many people found this effective that there must be something to it,and Todd Becker, blogger from Getting Stronger whom I respect greatly, speaks highly of this method. I've yet to try it, it's on my list. Curious, did both these methods kickstart or break a stall/plateau for you?

    2. The Shangri-La thing made it all possible. It dropped my appetite to the point where I could think and apply all the stuff I read online, which was mostly a low-carb paleo style approach. I was doing about 70 fat, 30 protein, 10 carbs, and I tried to keep my calories at 1500, except for that once a week treat I mentioned. Those macros weren't intentional, but I got interested in figuring out what they were after some internet conversations.
      Well after I lost the weight I started trying to work out and learned about what Keifer was saying. He actually does have a more reasonable version and then the tricked out bodybuilder version. I realized what I perceived as cheats had probably helped me lose weight, while the longer stretches of dieting did not and may have harmed me. I use it now, intentionally to help me gain muscle, but I had lost the weight before I heard of Keifer. I didn't get into the gym until afterwards either.

  2. Beautifully clear description of this "dance of the transmitters," Kindke! I wish all writers on the subject did as good a job....

  3. I suspect the modern fashion for thinness and the popularity of dieting contributed substantially to the obesity epidemic. Crush dieting (especially combined with intense exercise) is almost the best thing you can do if you want to gain weight higher than it is predisposed genetically. The advice to follow a diet which increases hunger and snacking behavior also contributed nicely.