FIG. 1.

Metabolic and molecular effects of smoking (4–11). Nicotine inhibits hypothalamic AMP-activated protein kinase (AMPK) activity, decreases food intake, and increases thermogenesis. Nicotine enhances lipolysis and increases the delivery of FFA to the liver and skeletal muscle. These effects of nicotine are associated with increased hepatic VLDL secretion and intramyocellular lipid (IMCL) saturation as well as peripheral insulin resistance. Nicotine increases mTOR/p70S6 K activity in cultured L6 myotubes in association with increased IRS-1 Ser 636 phosphorylation and reduced insulin-stimulated glucose uptake, and mTOR inhibitor rapamycin blocks these effects of nicotine. NAchR, nicotinic acetylcholine α1 receptors; P, phosphorylation.