Tag Archives: leptin

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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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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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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Non-sequiter nutrition II, a sugar-thought experiment

The average western diet contains about 50 grams of fructose from a variety of sources ranging from beneficial fibrous fruits to the more insidious sugar-sweetened beverages, soda and juice.  50 grams of fructose.   2 1/2 cans of Coca-Cola.

50 grams x 4 kcal/g = 200 kcal

200 kcal / 2,000 kcal = 10%

10% of your calories are provided by fructose

Even the very high end of fructose intake rarely exceeds ~85 grams, which is still < 20%.  My point?   This is nowhere near the 60% used in mouse diet studies.  Disclaimer: I think fructose causes leptin resistance because of data from such studies.  60% fructose is the fructose that causes leptin resistance and increased susceptibility to obesity.  What does this say about “normal” levels of fructose intake?  Toxic doses cause leptin resistance and obesity susceptibility in mice, well, because they’re toxic, and fructose toxicity just so happens to manifest like that (in mice).   60% is toxic.  15 cans of Coca-Cola per day (depending on who’s counting); but is it relevant?

39 grams of sugar, roughly half of which is fructose

In mouse studies, toxic doses are used for practical reasons- it’s cheap.  The animals can be rendered leptin resistant, glucose intolerant, and susceptible to obesity within a few months of feeding this expensive purified synthetic diet.  This probably (probably) takes over 100 times longer in humans simply because it’s nearly impossible for humans to ingest mouse-toxic-levels of fructose.

1. If the dose was based on body weight (like a drug; e.g., mg/kg or mpk):

60% fructose x 12 kcal/d = 7.2 kcal.  Divided by 4 kcal/g = 1.8 grams per day.

1.8 grams for a 40 g mouse = 45 g/kg.  For a 70 kg (154 lb) human = 3,150 grams of fructose or roughly 12,600 kcal.  I.e., 150 cans of soda or about a week’s worth of calories.  In other words, you’d have to eat a hypercaloric fructose-only diet for months.

2. If the dose was based on calories:

60% fructose x 2,000 kcal/d = 300 grams = 15 cans of soda or doughnuts per day.   News flash: that’s gross, but it won’t kill you.

fructose: still not as dangerous as playing in traffic

How about just lowering your lifetime sugar exposure.  39 grams of sugar is worse than 0.01 grams of stevia or sucralose.  Anyone remember “water?”  Even if you believe “a calorie is a calorie,” exclusively, it’s still really hard to burn off 39 grams of sugar.  Try running 2 miles.  Skinny kids might do this automatically after drinking a can of soda or eating a doughnut.  Not most adults.

Don’t play in traffic either.

calories proper