Mechanisms of leptin resistance revealed

Mechanisms of leptin action and leptin resistance.

The adipose tissue-derived hormone leptin acts via its receptor (LRb) in the brain to regulate energy balance and neuroendocrine function. LRb signaling via STAT3 and a number of other pathways is required for the totality of leptin action. The failure of elevated leptin levels to suppress feeding and mediate weight loss in common forms of obesity defines a state of so-called leptin resistance....

Editorial: Leptin Resistance in Metabolic Disorders: Possible Mechanisms and Treatments

HF diets increase hypothalamic PTP1B and induce leptin resistance through both leptin-dependent and -independent mechanisms.

Protein tyrosine phosphatase 1B (PTP1B) contributes to leptin resistance by inhibiting intracellular leptin receptor signaling. Mice with whole body or neuron-specific deletion of PTP1B are hypersensitive to leptin and resistant to diet-induced obesity. Here we report a significant increase in PTP1B protein levels in the mediobasal hypothalamus (P = 0.003) and a concomitant reduction in leptin ...

Leptin receptor signaling: pathways to leptin resistance.

The identification of spontaneous mutations in the leptin- and leptin receptor (ObR)-encoding ob and db gene, respectively, opened up a new field in obesity research. Leptin, an adipocyte-derived hormone, mirrors the body's fat stores and thereby informs the brain about the body's energy status. In the hypothalamus, leptin triggers specific neuronal subpopulations, like POMC and AgRP/NPY neuron...

Addressing leptin resistance.

LEPTIN WAS CLONED IN 1994 and shown to be secreted from adipocytes (5). This and subsequent studies demonstrated that leptin is made and secreted in proportion to the fat content of individual adipocytes (4). Under normal physiological conditions, the concentration of circulating leptin is inversely related to body fat, or energy, content (2). It is transported past the bloodbrain barrier and a...