We propose that this expanded framework for understanding the mechanisms underlying leptin deficiency arising from genetic mutations may be useful in designing therapeutics for leptin-associated disorders.
However, short-term leptin substitution can increase the blood pressure and heart rate in obese humans with leptin deficiency, indicating that leptin plays at least an additive role in obesity-associated hypertension.
Children with rare homozygous mutations in the leptin gene and complete leptin deficiency develop extreme hyperphagia and obesity soon after birth but respond with normal eating and a selective loss of excess body fat upon being given small amounts of leptin.
Our data show that similar to findings in obese humans, homozygous or heterozygous leptin deficiency is associated with increased platelet aggregation compared with controls, and that higher concentrations of leptin do not increase platelet aggregation.
The only situation in which obesity does not parallel leptin values is the rare case of morbid obesity due to leptin deficiency caused by missense mutation of the leptin gene.
With the exception of ob/ob mice, circulating plasma leptin is elevated in all other obese rodents as well as in obese humans, suggesting that leptin resistance rather than leptin deficiency is a characteristic feature of obesity.
Preterm delivery leads to premature separation from the maternal and placental leptin source predisposing infants to postnatal leptin deficiency, but this has not been fully described.
Recombinant methionyl human leptin (metreleptin) therapy was shown to improve hyperglycaemia, dyslipidaemia and insulin sensitivity in patients with lipodystrophic syndromes, but its effects on insulin secretion remain controversial.We used dynamic intravenous (i.v.) clamp procedures to measure insulin secretion, adjusted to insulin sensitivity, at baseline and after 1 year of metreleptin therapy, in 16 consecutive patients with lipodystrophy, diabetes and leptin deficiency.
Our objective in the present study was to examine the rate of melanoma tumor growth in lean and obese mice with leptin deficiency or high levels of plasma leptin.
Plasma leptin in humans is positively correlated with body fat mass, suggesting that leptin resistance rather than leptin deficiency is a common feature of human obesity.
While leptin replacement therapy fails to provide substantial benefit in common obesity, it is an effective treatment for congenital leptin deficiency and states of acquired leptin deficiency such as lipodystrophy.
The subcutaneous administration of recombinant human leptin has major and sustained beneficial effects on the multiple phenotypic abnormalities associated with congenital human leptin deficiency.
This dual-cassette vector achieves highly selective transduction of visceral fat while severely restricting off-target transduction of liver.As proof of efficacy, i.p. administration of an adipose-targeting Rec2 vector harboring the leptin gene corrects leptin deficiency, obesity, and metabolic syndromes of <i>ob</i>/<i>ob</i> mice.
Leptin deficiency in mice counteracts imiquimod (IMQ)-induced psoriasis-like skin inflammation while leptin stimulation induces inflammation in human keratinocytes.
The observation of leptin deficiency in patients with lipodystrophy and the potential of leptin replacement to rescue metabolic abnormalities in animal models of lipodystrophy were followed by the first clinical study of leptin therapy in patients with severe lipodystrophy.
Experimental studies using animal models of a low leptin state such as leptin deficiency have shown that leptin regulates sleep architecture, upper airway patency, ventilatory function, and hypercapnic ventilatory response.
Leptin is not able to treat typical obesity; however, it is effective for reversing leptin deficiency-induced obesity and is possibly useful in lipodystrophy.
Because uncontrolled diabetes is associated with both leptin deficiency and hyperglucagonemia, and because intracerebroventricular (ICV) leptin administration reverses both hyperglycemia and hyperglucagonemia in this setting, we hypothesized that deficient leptin inhibition of LPBNCCK neurons drives activation of this LPBN→VMN circuit and thereby results in hyperglucagonemia.
The leptin staining intensity suggested that ART alone may lead to increased leptin expression, whereas ART combined with a HCD may cause leptin deficiency.
Our results support the idea that leptin modulates insulin sensitivity and glucose disposal independently of its effect on food intake, and that leptin deficiency accounts for the insulin resistance found in CGL.