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Circumventing central leptin resistance: lessons from central leptin and POMC gene delivery

Zhang Y, Scarpace PJ2006PeptidesReview
10.1016/j.peptides.2005.01.024PubMed
CardiovascularEndocrine (ADH/ACTH/MSH)GastrointestinalHypothalamic-PituitaryImmune/InnateMusculoskeletalNeurologicalOcularRespiratory/Sinus
Bacterial EndotoxinsIndoor Mold (Stachybotrys, Aspergillus, etc.)MycotoxinsVolatile Organic Compounds (VOCs)Water-Damaged Buildings (WDB)

Abstract

We identified that leptin resistance in aged-obese rats has both peripheral and central components. The central resistance is characterized by diminished hypothalamic leptin receptors and impaired leptin signal transduction. We developed a new model of leptin-induced leptin resistance in which application of the central leptin gene delivery produces unabated hypothalamic leptin over-expression. The chronic central elevation of leptin precipitates leptin resistance in young animals devoid of obesity and exacerbates it in mature or aged animals with obesity. Despite leptin resistance, our aged obese, DIO, and leptin-induced leptin resistant rats were fully responsive to central pharmacological melanocortin activation. We propose that the central leptin resistance resides between leptin receptor and melanocortin receptor activation. Our central POMC gene therapy overcame leptin resistance, producing weight and fat loss and improved insulin sensitivity in obese Zucker and aged rats. This success highlights the central melanocortin system as a useful drug target for combating obesity.

Part of Endotoxins research, Mold & water-damaged buildings research, Mycotoxins research, CIRS biomarkers research · Curated by Lauren Lowenstein, The Biotoxin Lady

Key Biomarkers

IgELeptinMMP-9Pulmonary function (FVC, FEV1/FVC)VEGFVisual Contrast Sensitivity (VCS)α-MSH

Symptom Clusters

Dermatological: unusual skin sensitivityFatigue, weakness, general malaiseGastrointestinal: abdominal pain, diarrheaHypothalamic: excessive thirst, frequent urination, night sweats, mood swings, appetite swings, temperature regulation abnormalitiesMusculoskeletal: aches, cramps, joint pain, morning stiffnessNeurological: headache, numbness, tingling, vertigo, memory loss, concentration difficulty, confusion, word-finding difficulty, disorientationOcular: light sensitivity, red eyes, blurred vision, tearingOther: metallic taste, static/shocksRespiratory/Sinus: sinus congestion, cough, shortness of breath

Cited By (2)

References (1)

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