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Leptin and Thyroid Hormone Regulate Hepatic Lipid Trafficking into Macro‐ and Microvesicular Pools
Author(s) -
Reno Candace,
Fehn Richard
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a699-c
Subject(s) - endocrinology , medicine , leptin , lipogenesis , very low density lipoprotein , chemistry , lipid droplet , lipid metabolism , hormone , biology , cholesterol , lipoprotein , obesity
Ultrastructural analysis of lipid vesicle populations by TEM and light microscopy show lipid trafficking patterns in normal and obese mice (C57BL/6J lep ob ) treated for 9 days with combinations of leptin, thyroid hormone (T 3 ), iopanoic acid (reduces thyroxine deiodination), and 6‐Hydroxydopamine (blocks peripheral sympathetic neurons). Hepatic lipids selectively traffick into the VLDL export pathways in response to hormones that characterize a well‐fed nutritional status (leptin and T 3 ) but are diverted to a distinct microvesicular pool with hypernutrition (elevated T 3 ). Endocrine profiles associated with hyponutrition (low 5′Monodeiodinase activity, decreased T 3 , leptin deficiency) promote macrovesicular storage due to reduced VLDL export and/or reduced adrenergic receptor‐mediated macrovesicle breakdown. In the case of nonalcoholic fatty liver disease (NAFLD), it is likely that the bottlenecking of VLDLs at the site of export leads to excess microvesicular storage or, alternatively, a reduction in macrovesicular breakdown for VLDL export. We propose an integrated model of hepatic lipid trafficking in which leptin promotes mobilization of both stored and newly‐synthesized lipids into the VLDL export pathway through direct and sympathetic‐mediated mechanisms while T 3 directly promotes lipogenesis and microvesicle formation plus indirectly retains both micro‐ and macrovesicles.