Our previous study (10) revealed that receptor cells of the taste sensory system were affected by leptin. The db/db mouse, which has defects in the functional receptor Ob-Rb, displays enhanced neural responses and elevated behavioral preference to sweet stimuli (20, 21) because of defects in leptin suppression of sweet responses in the taste system that healthy mice normally possess (10, 27). Here, we showed expression of the functional Ob-Rb receptor in taste cells of lean and ob/ob mice but not in the db/db mice. By binding the receptor in taste cells, the hormone partially suppresses taste cell responses and inhibits afferent signals indicating sweet taste. The blunting of sweet taste leads to a decrease in consumption of sweet solutions in mice demonstrated by the present study. Thus, leptin may influence food intake not only through the central nervous system but also at a peripheral level acting as a sweet-sensing modulator. http://ajpregu.physiology.org/cgi/content/full/293/4/R1468
Leptin reduces body fat selectively, sparing body protein. Accordingly, during chronic leptin administration, food intake is suppressed, and body weight is reduced until body fat is depleted. Body weight then stabilizes at this fat-depleted nadir, while food intake returns to normal caloric levels, presumably in defense of energy and nutritional homeostasis. This model of leptin treatment offers the opportunity to examine controls of food intake that are independent of leptin's actions, and provides a window for examining the nature of feeding controls in a "fatless" animal. Here we evaluate macronutrient selection during this fat-depleted phase of leptin treatment. Adult, male Sprague-Dawley rats were maintained on standard pelleted rodent chow and given daily lateral ventricular injections of leptin or vehicle solution until body weight reached the nadir point and food intake returned to normal levels. Injections were then continued for 8 days, during which rats self-selected their daily diet from separate sources of carbohydrate, protein, and fat. Macronutrient choice differed profoundly in leptin and control rats. Leptin rats exhibited a dramatic increase in protein intake, whereas controls exhibited a strong carbohydrate preference. Fat intake did not differ between groups at any time during the 8-day test. Despite these dramatic differences in macronutrient selection, total daily caloric intake did not differ between groups except on day 2. Thus controls of food intake related to ongoing metabolic and nutritional requirements may supersede the negative feedback signals related to body fat stores.
Insulin is a general storage hormone, yes. But, glucose is special
. Transporting glucose into a cell, or protein, or, fat, why would you expect all of these actions to have the same consequences? The carbohydrate hypothesis does not depend on Alan Aragon's understanding of insulin, there's more to it than that.
A lot of diets are popping up extolling the virtues of high carb for serotonin. I found this yesterday;http://cmbi.bjmu.edu.cn/news/report/2009/pdf/med09_09_1.pdf
I understand this study even less than I do the last two I posted. :shock: But look at the title;
"A Serotonin-Dependent Mechanism Explains
the Leptin Regulation of BoneMass,
Appetite, and Energy Expenditure"
Here's the bit I understand. In pre-vertebrates, serotonin is a "hunger" hormone, promoting food consumption. In humans and other boned creatures, brain-serotonin has been described as a satiation-hormone, but I don't think that's correct. You eat carbs; protein is sucked into your muscles, etc; blood tryptophan goes up, tryptophan transport into the brain goes up, serotonin goes up. You stop eating according to this theory, once you get that serotonin "buzz". But-- pursuing that serotonin buzz, wouldn't that be part of the conditioned response that set off the feeding behaviour in the first place? The rats in that second study I posted don't seem to be interested in carbs, with all that extra leptin. So, in vertebrates, maybe the direct stimulus of serotonin that occurs in more primitive creatures is rerouted into a conditioned response, with eventually the same consequence, weight gain. Or maybe the theory that serotonin is a satiation hormone at all is simply a myth. Seratonin tells you you've had enough bread in much the same way dopamine lets you know when you've had enough cocaine. :?
Leptin inhibition of bone mass accrual requires the
integrity of specific hypothalamic neurons but not
expression of its receptor on these neurons. The
same is true for its regulation of appetite and energy
expenditure. This suggests that leptin acts elsewhere
in the brain to achieve these three functions.Weshow
here that brainstem-derived serotonin (BDS) favors
bone mass accrual following its binding to Htr2c
receptors on ventromedial hypothalamic neurons
and appetite via Htr1a and 2b receptors on arcuate
neurons. Leptin inhibits these functions and increases
energy expenditure because it reduces serotonin
synthesis and firing of serotonergic neurons. Accordingly,
while abrogating BDS synthesis corrects the
bone, appetite and energy expenditure phenotypes
caused by leptin deficiency, inactivation of the leptin
receptor in serotonergic neurons recapitulates them
fully. This study modifies the map of leptin signaling
in the brain and identifies a molecular basis for the
common regulation of bone and energy metabolisms.
Knocking out brain derived serotonin in leptin deficient mice keeps them from becoming obese, but it also ruins their bones. Leptin decreases appetite at least partly by decreasing the action of serotonin.
Leptin resistance could mean stronger bones. Which makes sense, larger people need stronger bones. Weight bearing exercise? Eating carbs isn't the only thing that promotes muscle synthesis, which clears proteins that compete with tryptophan for uptake into the brain. Lift weights, serotonin maybe goes up, appetite goes up, bones get stronger, muscles get bigger... and maybe, depending on your personal metabolism, there's a lot of stuff going on, you even get fatter