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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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Leptin regulates bone formation via the sympathetic nervous system

We previously showed that leptin inhibits bone formation by an undefined mechanism. Here, we show that hypothalamic leptin-dependent antiosteogenic and anorexigenic networks differ, and that the peripheral mediators of leptin antiosteogenic function appear to be neuronal. Neuropeptides mediating leptin anorexigenic function do not affect bone formation. Leptin deficiency results in low sympathetic tone, and genetic or pharmacological ablation of adrenergic signaling leads to a leptin-resistant high bone mass. beta-adrenergic receptors on osteoblasts regulate their proliferation, and a beta-adrenergic agonist decreases bone mass in leptin-deficient and wild-type mice while a beta-adrenergic antagonist increases bone mass in wild-type and ovariectomized mice. None of these manipulations affects body weight. This study demonstrates a leptin-dependent neuronal regulation of bone formation with potential therapeutic implications for osteoporosis.

NASA Discipline Regulatory Physiology↗

A new perspective on adiposity in a naturally obese mammal

Many mammals seasonally reduce body fat due to inherent periods of fasting, which is associated with decreased leptin concentrations. However, no data exist on the correlation between fat mass (FM) and circulating leptin in marine mammals, which have evolved large fat stores as part of their adaptation to periods of prolonged fasting. Therefore, FM was estimated (by tritiated water dilution), and serum leptin and cortisol were measured in 40 northern elephant seal (Mirounga angustirostris) pups early (<1 wk postweaning) and late (6-8 wk postweaning) during their natural, postweaning fast. Body mass (BM) and FM were reduced late; however, percent FM (early: 43.9 +/- 0.5, late: 45.5 +/- 0.5%) and leptin [early: 2.9 +/- 0.1 ng/ml human equivalents (HE), late: 3.0 +/- 0.1 ng/ml HE] did not change. Cortisol increased between early (9.2 +/- 0.5 microg/dl) and late (16.3 +/- 0.9 microg/dl) periods and was significantly and negatively correlated with BM (r = 0.426; P < 0.0001) and FM (r = 0.328; P = 0.003). FM and percent FM were not correlated (P > 0.10) with leptin at either period. The present study suggests that these naturally obese mammals appear to possess a novel cascade for regulating body fat that includes cortisol. The lack of a correlation between leptin and FM may reflect the different functions of fat between terrestrial and marine mammals.

Non-NASA Center↗

Dietary fat intake, supplements, and weight loss

Although there remains controversy regarding the role of macronutrient balance in the etiology of obesity, the consumption of high-fat diets appears to be strongly implicated in its development. Evidence that fat oxidation does not adjust rapidly to acute increases in dietary fat, as well as a decreased capacity to oxidize fat in the postprandial state in the obese, suggest that diets high in fat may lead to the accumulation of fat stores. Novel data is also presented suggesting that in rodents, high-fat diets may lead to the development of leptin resistance in skeletal muscle and subsequent accumulations of muscle triacylglycerol. Nevertheless, several current fad diets recommend drastically reduced carbohydrate intake, with a concurrent increase in fat content. Such recommendations are based on the underlying assumption that by reducing circulating insulin levels, lipolysis and lipid oxidation will be enhanced and fat storage reduced. Numerous supplements are purported to increase fat oxidation (carnitine, conjugated linoleic acid), increase metabolic rate (ephedrine, pyruvate), or inhibit hepatic lipogenesis (hydroxycitrate). All of these compounds are currently marketed in supplemental form to increase weight loss, but few have actually been shown to be effective in scientific studies. To date, there is little or no evidence supporting that carnitine or hydroxycitrate supplementation are of any value for weight loss in humans. Supplements such as pyruvate have been shown to be effective at high dosages, but there is little mechanistic information to explain its purported effect or data to indicate its effectiveness at lower dosages. Conjugated linoleic acid has been shown to stimulate fat utilization and decrease body fat content in mice but has not been tested in humans. The effects of ephedrine, in conjunction with methylxanthines and aspirin, in humans appears unequivocal but includes various cardiovascular side effects. None of these compounds have been tested for their effectiveness or safety over prolonged periods of time.

NASA Discipline Musculoskeletal↗