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Existing and Emerging Molecular Targets for the Pharmacotherapy of Obesity - Endotext - NCBI Bookshelf

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(domain 176–191 is insufficient) IGF-1-independent mechanism: no growth/anabolic effects Direct lipolysis: hormone-sensitive lipase (HSL) activation Perilipin: phosphorylation and release of lipase access to triglycerides Lipid Metabolism Modulation: β-Oxidation: 35-45% increase in mitochondrial fatty acid oxidation CPT-1 (carnitine palmitoyltransferase): upregulation of FA entry into mitochondria Lipogenesis: inhibition of new fat synthesis (↓ acetyl-CoA carboxylase) Gene expression: modulation of PPARα, PGC-1α (metabolism regulators) Adipocyte-Specific Effects: Preference for visceral vs subcutaneous adipose tissue Adipocyte size reduction: 25-35% cell diameter Adipocyte apoptosis: increased programmed cell death in pathological fat Adiponectin: increased secretion of anti-inflammatory adipokine Pharmacokinetics: SC Bioavailability: 80–85% Absorption: rapid, Tmax 20-30 minutes Half-life: 30–60 minutes (short) Distribution: preferential to adipose tissue Elimination: rapid renal clearance, no active metabolites Effect duration: 4-6 hours post-administration 🔹 APPLICATIONS, MECHANISMS, AND EXTENDED RESEARCH SELECTIVE BODY FAT REDUCTION Weight and Visceral Fat Loss: Preclinical Rodent Studies: Body weight reduction: 50–55% higher than controls (12 weeks, obese rats) Visceral fat: reduction with 65-70% vs