Fasting leptin and appetite responses induced by a 4-day 65%-energy-restricted diet.

OBJECTIVE: Animal studies show that the leptin decline after acute severe caloric restriction is a peripheral signal to increase food intake. However, most human studies have failed to observe such a relationship. We studied the acute effects of severe caloric restriction on the association between serum leptin concentrations and subjective appetite. SUBJECTS: A total of 44 healthy adult men (aged: 43 +/- 5 years; BMI: 27.3 +/- 3.2 kg/m(2)). MEASUREMENTS: Fasting serum leptin concentrations and self-perceived appetite levels were measured during a 4-day diet containing 36% of the estimated energy requirements. Appetite levels were assessed with a 10-point Likert scale, reflecting hunger, fullness, desire to eat, prospective consumption and total appetite. RESULTS: After the 4-day energy deficit, fasting leptin concentrations decreased by 39.4% (95% CI: -43.6; -34.9%). This decline was associated with an increase in fasting hunger (r = -0.42; P < 0.01), desire to eat (r = -0.39; P < 0.05) and total appetite (r = -0.38; P < 0.05). Furthermore, the association between fasting leptin concentrations and fasting appetite levels became stronger during the energy restriction period (for total appetite: day 0 r = -0.15, P = 0.32; day 2 r = -0.31, P =< 0.05; day 4 r = -0.41, P < 0.01). CONCLUSIONS: The acute proportional reduction in fasting leptin after 4-day energy restriction is associated with an increase in self-perceived appetite. Additionally, the inverse association between proportional fasting leptin concentrations and self-perceived appetite response becomes stronger as energy restriction is prolonged. These findings suggest that leptin has an instrumental role in restoring energy balance in humans through the expression of appetite

Estrogen deficiency causes central leptin insensitivity and increased hypothalamic neuropeptide Y

OBJECTIVE: Altered fat distribution is a consequence of menopause, but the mechanisms responsible are unknown. Estrogen insufficiency in humans can be modeled using ovariectomized rats. We have shown that increased adiposity in these rats is due to reduced physical activity and transient hyperphagia, and can be reversed with 17β-estradiol treatment. The aims of this study were to examine whether this altered energy balance is associated with circulating leptin insufficiency, central leptin insensitivity, decreased hypothalamic leptin receptor (Ob-Rb) expression, and/or increased hypothalamic neuropeptide Y (NPY). METHODS: Plasma leptin levels, adipose tissue ob gene expression, energy balance responses to i.c.v. leptin, hypothalamic Ob-Rb expression and NPY concentration in five separate hypothalamic regions were measured in adult female rats after either ovariectomy or sham operations. RESULTS: Obesity was not associated with hypoleptinemia or decreased ob gene expression in ovariectomized rats; however, it was associated with insensitivity to central leptin administration. Food intake was less suppressed and spontaneous physical activity was less stimulated by leptin. This was not due to decreased hypothalamic Ob-Rb expression. NPY concentration in the paraventricular nucleus of the hypothalamus was elevated in the ovariectomized rats, consistent with leptin insensitivity; however this effect was transient and disappeared as body fat and leptin levels increased further and hyperphagia normalized. CONCLUSION: Impaired central leptin sensitivity and overproduction of NPY may contribute to excess fat accumulation caused by estrogen deficiency.DA Ainslie, MJ Morris, G Wittert, H Turnbull, J Proietto and AW Thorbur