Category Archives: Leptin

Paleo Plants and Carnivory

From what I gather, it’s been difficult to pinpoint the role of plants in the diet of our ancestors for a variety of reasons.  For example, evidence of plants on cooking tools and dental remains is suggestive but doesn’t disprove the possibility that said evidence came from preparing the plants for some other purpose (eg, tools, weapons, or medicine), or that the stomach contents of an herbivore was ingested (which gets partial credit).

That said, after reviewing a few studies on the topic (see below), it’s safe to say that plants were eaten, probably frequently, and the types & quantities varied seasonally & geographically.  Collectively, the data suggest we aren’t carnivores.

…you had to have something to hold you over until the next fish fell prey to your deadly hunting spear…  

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Melatonin is the chemical expression of darkness.

Melatonin is secreted from the pineal gland, the seat of the soul, the third eye.   Pinealectomy induces circadian arrhythmia and has interesting effects on adipose tissue biology.

Exhibit A.  In 2004, Alonso-Vale and colleagues showed that 6 weeks after pinealectomy, [melatonin-deficient] rats subjected to fasting exhibited an impaired energy conservation response.  That is, they lost more weight and significantly depleted their adipocytes:


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The incredible camping experiment, circadian proper

Entrainment of the Human Circadian Clock to the Natural Light-Dark Cycle (Wright et al., 2013)

Abstract (edited): The electric light is one of the most important human inventions. Sleep and other daily rhythms in physiology and behavior, however, evolved in the natural light-dark cycle, and electrical lighting is thought to have disrupted these rhythms. Yet how much the age of electrical lighting has altered the human circadian clock is unknown. Here we show that electrical lighting and the constructed environment is associated with reduced exposure to sunlight during the day, increased light exposure after sunset, and a delayed timing of the circadian clock as compared to a summer natural 14 hr 40 min:9 hr 20 min light-dark cycle camping. Furthermore, we find that after exposure to only natural light, the internal circadian clock synchronizes to solar time such that the beginning of the internal biological night occurs at sunset and the end of the internal biological night occurs before wake time just after sunrise

In other words, they compared circadian events during 2 weeks of normal life to 2 weeks of 100% camping.  And camping won.

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Summer is fattening. Don’t do it in winter.

Seasonal eating proper

More from T.S. Wiley and Dr. Kruse on seasonal eating in what appears to be the primary model for its justification for use in humans – hibernating mammals.

How it goes, or so they say: in summer, hibernators massively overeat, including carb-rich foods, in order to generate muscle and liver insulin resistance, so as to promote body fat growth.  The long light cycle reduces evening melatonin, which pushes back the usual nighttime peak in prolactin, which causes an abnormal resistance to leptin, which induces hypothalamic NPY and subsequent carbohydrate craving.  Ergo, summer is fattening.  In today’s day, increased artificial lights guarantee year-round pseudo-summer; and we no longer experience the benefits of the short light cycle: longer sleep times (akin to hibernation) and fasting – either complete fasting as in hibernation, or pseudo-fasting, ie, a ketogenic diet.

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Energy Balance > CICO

The regulation of energy balance is a long-term process, and it can’t be maintained by counting calories on a day-to-day basis.  Taubes once wrote that exercise doesn’t cause weight loss because it builds up an appetite, so you end up sucking down a Starbuck’s Jumbo Calorie Bomb on the way home from doing Yoga at the gym.  This is probably somewhat true, but this little gem from 1955 exposes some very interesting nuances.

Edholm(Edholm et al., 1955)

These researchers rigorously measured food intake and did a comprehensive assessment of energy expenditure during a wide variety of activities – lying down, standing, walking, gun cleaning, stair climbing, dressing, etc., etc.

Divide and conquer

The individual differences: big people expend more energy on life.  most of the time.

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Silent Leptin Resistance

Conventional leptin resistance has something do with obesity.  It is known.  Silent leptin resistance is … err … complicated. 

Divide and conquer

Fructose-induced leptin resistance exacerbates weight gain in response to subsequent high-fat feeding (Shapiro, Scarpace, et al., 2008 AJP)

A remarkable 60% fructose diet fed to rats for 6 months had absolutely no effect on energy balance.  Nil. QED.
Fig 1

Food intake and body weight were unaffected because the levels of and sensitivity to endogenous leptin were identical in both groups.

Enter the Dragon

Enter the Dragon

“Silent Leptin Resistance” – The fructose-fed rats are, however, profoundly resistant to the satiating effects of Metreleptin (a pharmaceutical grade injectable leptin analog):

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“When we block the D2 receptor in humans, it is expected they will develop glucose intolerance, obesity, and sedentary behavior.” -Jane Plain, in her series on The physiology of body fat regulation.  It’s probably true.

Randomized pilot study of cabergoline, a dopamine receptor agonist: effects on body weight and glucose tolerance in obese adults (Gibson et al., 2012)

Cabergoline is primarily used to treat prolinactinoma, or prolactin-secreting tumors.  In women (& men apparently), prolactin stimulates milk production; in men, it is associated with the refractory period after orgasm.  In both genders, dopamine inhibits prolactin secretion.  Cabergoline targets the D2 receptor, but it’s a dirty drug.  It’s used off-label for gyno and to improve sexy times (Kruger et al., 2003 <– yes, that was actually tested).

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salt makes you thirsty, soda makes you hungry.

As previously discussed, DRINK was a randomized intervention study that gave children either regular or diet soda for a year and surprise surprise, the regular soda drinkers gained about more body fat than the diet soda drinkers (de Ruyter et al., 2012).  And in the follow-up, with an opposite study design, overweight & obese children who continued to drink regular soda gained twice as much weight as those who cut their intake (Ebbeling et al., 2012).  There was no apparent black box in the latter study as the kids who stopped drinking soda also decreased their intake of other foods…

-does not compute-fructose

wait a minute … By switching from regular soda to diet, you just end up compensating by eating more of something else, right?  My initial response to that has always been that it doesn’t matter – ANYTHING else is better than a straight shot of 100% HFCS (+ some other chemicals).  But those kids didn’t do that.  they ate less of other foods.


Does HFCS soda make you eat more?

A recent study has put a little more fuel on this fire.  Similar to the abovementioned two, it’s not a sophisticated study designed to accurately assess the impact of regular soda on appetite, satiety, hunger, etc., but it supports the theory that diet soda negative calories are NOT compensated for by eating more of something else.

Food and beverages associated with higher intake of sugar-sweetened beverages (Mathias et al., 2013)

It was another big cross-sectional NHANES study that simply asked how much regular soda, diet soda, and other foods kids were eating.Mathias data 1

They showed that as soda intake increased, so did total calories, which could simply mean the soda was adding calories to their diets.  This would indirectly support the opposite of the above mentioned theory, namely, that soda calories aren’t compensated for.  But it gets better (or worse, depending how you look at it):Mathias data 2

soda didn’t simply add to the total calorie intake.  More often than not, calorie intake increased above and beyond that contributed by the soda.  And it wasn’t just that bigger kids were drinking more soda and eating more food – these data were controlled for body weight.  The authors estimated that for every 100 kcal of soda drank, an additional 36 – 86 kcal of food was eaten.

salt makes you thirsty, and now soda makes you hungry?

calories proper


Obesity is not permanent

Take a group of obese people (> 250 lbs) and put them on a massive calorie restricted diet.  They lose weight and metabolic rate plummets.  Weight loss fail?  In most cases, yes.  But a recent study showed that the decrepit post-weight loss metabolic rate gradually improves in parallel with an increase in dietary fat ingestion to such a degree that even after two long years: totally food intake was almost back to normal, energy expenditure improved, and all this happened despite continual weight loss.  In other words, obesity is not permanent. 

creme brulee

Decreased energy density and changes in food selection following Roux-en-Y gastric bypass (Laurenius et al., 2013)

Statistically speaking, no diet on Earth comes close to RYGB in terms of weight loss success.  Long term.  Seemingly permanent.  It’s the closest thing to a cure we’ve got.


Body weight is down by 30%, and energy expenditure is rising faster than a speeding bullet.  because food intake is increasing while body weight is dropping – they’re probably more active too ** weight loss than more exercise –

But there’s a more mystical aspect to RYGB that warrants attention.  (it could be the increasing fat intake, but for now let’s just say it’s RYGB per se).  According to this pearl, weight loss of only 10% via diet alone causes energy expenditure crash by 394-500 kcal/d, and physiological replacement of leptin via subcutaneous injection can increase this by 234-454 kcal/d (Rosenbaum, Murphy, Heymsfield, Matthews, and Leibel, 2002).

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Don’t eat doughnuts for breakfast, Op. 85

Weight-loss maintenance, part 1

“Weight-loss maintenance” is a critical part in the battle against obesity because losing weight is much easier and significantly more successful than keeping it off.  The difference lies predominantly in duration: a few months of dieting to lose weight vs. keeping it off for the rest of your life.  Two diet studies on the topic were recently published, and while neither study really addressed the issue proper, some interesting points can be gleaned from both.

Study #1

Meal timing and composition influence ghrelin levels, appetite scores and weight loss maintenance in overweight and obese adults (Jakubowicz et al., 2012)

16 weeks of weight loss followed by 16 weeks of “weight-loss maintenance.”

In brief, the weight loss was accomplished by one of two hypocaloric (1400 kcal/d) isocaloric pseudo-Dukan Diets (higher protein & lower fat than Atkins)

The catch:  Breakfast for the people in HCPb (High Carbohydrate and Protein breakfast)  had twice the calories, 6x the carbs, and half more protein than LCb (Low Carb breakfast).  This was compensated, calorically, by a much smaller dinner.  In other words, they ate like a King for breakfast, a Prince for lunch, and a Pauper for dinner… with the added bonus of a “sweet food… chocolate, cookies, cake, ice cream, chocolate mousse or donuts.”  For breakfast.

People in both groups lost roughly similar amounts of weight in the weight loss phase:

During the first 16 weeks (weight loss phase), a strict 1400 kcal diet was implemented.  During the second 16 weeks (“weight-loss maintenance” phase), macronutrient composition was supposed to be kept similar, but subjects were “free to eat as motivated by hunger or cravings.”  Critique #1a: this study would’ve greatly benefitted by food intake questionnaires to know more accurately what these people were eating; the importance of this becomes more apparent soon.

At three times throughout the study (baseline, week 16, and week 32), a “Breakfast meal challenge” was administered to assess Hunger, Hatiety, and Food Cravings.  Unfortunately, however, the “Breakfast meal challenge” was administered… after… breakfast.  HCPb binged on a high calorie 3-course meal which included dessert while LCb nibbled on a lite breakfast… And the researchers needed a 100-millimeter Visual Analog Scale and 28-item Food Craving Inventory Questionnaire to figure out who would be hungrier afterwords?  Really?

Divide and conquer

Table 2.  There were no major differences between the groups, and between those who completed or didn’t complete the study except for weight loss in those who withdrew.  Apparently, people who didn’t lose any weight on the hypocaloric weight loss diet decided to quit (was it the diet or the dieter that didn’t work? [sorry, no offense]).  In any case, this would’ve introduced a systematic bias except the non-weight-losers were similar in both diet groups.  But Hunger & Satiety was also similar between completers and dropouts… I wonder why…  i.e., the diet was working for those who were losing weight, because Hunger was low and Satiety high; in the dropouts who didn’t lose weight, Hunger was low and Satiety high because they were eating more (which is why they didn’t lose weight).  IOW: “not hungry -> eat less -> lose weight -> complete the study” vs. “eat more -> not hungry -> don’t lose weight -> dropout of the study.”  People are “not hungry” in both groups, but for different reasons.

Critique 1b: this is another place where a food intake questionnaires would come in handy.

During the weight loss phase, LCb lost a little bit more weight and became a little bit more insulin sensitive than HCPb, which is interesting only because the macronutrients were so similar.  Thus, it may have been an effect of “meal-size-timing.”  In other words, don’t eat like a King for breakfast, a Prince for lunch, and a Pauper for dinner.

Ghrelin, a hunger hormone, was significantly higher in LCb and this actually correlated very well with measured Hunger levels (unlike leptin, the far more popular anti-hunger hormone, discussed in depth HERE).  And insulin, a theorized yet controversial hunger hormone, did not: insulin was lower at week 16 while Hunger was 2x higher; and insulin was 2x higher at week 32 compared to week 16 while Hunger was the same at those time points (Table 3).  Thus, for those interested (which is admittedly probably only me), neither leptin nor insulin correlate with Hunger levels; but this study showed that ghrelin does.  Furthermore, similar to those leptin data mentioned above, Hunger was not correlated with weight loss (which is kind-of-fascinating).

The second half of the study (“weight-loss maintenance”) was complete bollocks and made no sense whatsoever (you’ll see it on the evening news).  What you can conclude from this study, however: people following the moderately higher protein and lower carb pseudo-Dukan Diet (LCb) lost modestly more weight during the first 16 weeks than those following the more traditional higher carb version (HCPb).  BOTH diets were “high protein” and “low carb,” and people in BOTH groups lost a lot of weight (~30 pounds in 4 months).  The media hasn’t had their way this study [yet], but when they do, I’m sure the they’ll disagree.

Don’t eat doughnuts for breakfast, you heard it here first.


calories proper