Читать книгу Pathy's Principles and Practice of Geriatric Medicine - Группа авторов - Страница 374

Leptin is produced predominantly in adipose tissue and circulates in amounts directly related to the size of fat stores. It suppresses appetite and food intake. Congenital leptin deficiency in humans is a very rare cause of morbid obesity associated with hyperphagia, and leptin treatment produces substantial weight loss in these people. Most obese people, however, have elevated circulating leptin concentrations consistent with their increased fat mass. Leptin resistance is probably a feature of most human obesity, and leptin administration to obese people has resulted in only minor weight loss. Although adipose tissue leptin mRNA expression increases with age in mice and rats, studies in rats and pigs have not found an increase in serum leptin with ageing. Plasma leptin concentrations in humans often increase with ageing, to a large extent because of the increased fat mass that also accompanies ageing. Most studies show that adjustment for fat mass removes this effect.⁵⁰ This is certainly so in women; but in men, some but not all studies have shown ageing to be associated with an increase in circulating leptin levels, even allowing for fat mass. This appears to be because of age‐related decreases in circulating testosterone concentrations. After adjusting for fat mass, plasma leptin levels in men are inversely related to plasma testosterone, while testosterone therapy reduces and inhibition of testosterone production increases circulating leptin levels.⁵¹

Little is known about the effects of ageing on sensitivity to the effects of leptin. Circulating levels of the soluble leptin receptor do not change with age in humans. Resting energy expenditure and carbohydrate oxidation are predicted by fat‐free mass and serum leptin concentration in middle‐aged, premenopausal women, but the relationship between fat store size and plasma leptin is much weaker in older adults. Fasting normally dramatically suppresses plasma leptin concentrations, thus stimulating hunger. Reduced suppression of leptin levels by fasting has been reported in ageing rats. Conversely, food intake, fat mass, and insulin action are suppressed less by leptin administration in older than young rats. This suggests that ageing may be accompanied by leptin resistance, which would tend to increase food intake. The impact of human ageing on the effects of fasting on leptin levels and of leptin administration has not been reported.⁵²