Category Archives: Leptin

A brief explanation of Hall et al., ie, THE LOW CARB WAR

“Examination of acute shifts in energy balance by selectively reducing calorie intake from one macronutrient.”

Intro (1/2): please don’t read this study with the media headlines in your mind.  Don’t even pay any attention to the study’s title, abstract, intro, and discussion.  In no way did this study put low carb proper on the chopping block, regardless of what you’ve seen online or elsewhere.  Mmmkay?

 

Intro (2/2): if you want a lesson (or refresher) in Advanced Nutrition, check out the Supplemental Information: in formulating his mathematical models, Dr. Hall seemingly reviewed every single biochemical pathway and physiological variable ever invented.  Read it, for science.  Really.

 

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Ketosis is a hack: here’s why

There are multiple distinct flavors of diabetes/obesity, as evidenced by the fact that some people have: 1) impaired glucose tolerance (but normal fasting glucose); 2) others have impaired fasting glucose (but normal glucose tolerance); and 3) others have both.  This means there isn’t a linear relationship between these phenomena*.  There are also: 4) obese patients with normal glucose metabolism; and 5) lean patients with type 2 diabetes.

*I think the great Dr. Kraft may have missed some of the nuances here.

There is not 100% overlap among these, suggesting [confirming] distinct diabetes/obesity phenotypes (and probably causes & best treatments).

 

 

midnightsun

 

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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:

pinealectomy

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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 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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Dopamine

“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

 

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