title: Decreased visceral adiposity accounts for leptin effect on hepatic but not peripheral insulin action.
abstract: Leptin decreases visceral fat (VF) and increases peripheral and hepatic insulin action. Here, we generated similar decreases in VF using leptin (Lep), beta(3)-adrenoreceptor agonism (beta3), or food restriction (FR) and asked whether insulin action would be equally improved. For 8 days before the in vivo study, Sprague-Dawley rats (n = 24) were either fed ad libitum [control (Con)], treated with Lep or beta3 (CL-316,243) by implanted osmotic mini-pumps, or treated with FR. Total VF was similarly decreased in the latter three groups (Lep, 3.11 +/- 0.96 g; beta3, 2.87 +/- 0.48 g; and FR, 3.54 +/- 0.77 g compared with 6.91 +/- 1.41 g in Con; P < 0.001) independent of total fat mass (by (3)H(2)O) and food intake. Insulin (3 mU. kg(-1). min(-1)) clamp studies were performed to assess hepatic and peripheral insulin sensitivity. Decreased VF resulted in similar and marked improvements in insulin action on glucose production (GP) (Lep, 1.19 +/- 0.51; beta3, 1.46 +/- 0.68; FR, 2.27 +/-0.71 compared with 6.06 +/- 0.70 mg. kg(-1). min(-1) in Con; P < 0.001). By contrast, reduction in VF by beta3 and FR failed to reproduce the stimulation of insulin-mediated glucose uptake ( approximately 60%), glycogen synthesis ( approximately 80%), and glycolysis ( approximately 25%) observed with Lep. We conclude that 1) a moderate decrease in VF uniformly leads to a marked increase in hepatic insulin action, but 2) the effects of leptin on peripheral insulin action are not due to the associated changes in VF or beta3 activation.
authors.affiliation: Division of Geriatrics, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA. barzilai@aecom.yu.edu
authors.forename: N
authors.initials: N
authors.lastname: Barzilai
authors.forename: L
authors.initials: L
authors.lastname: She
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: Hu
authors.forename: P
authors.initials: P
authors.lastname: Vuguin
authors.forename: L
authors.initials: L
authors.lastname: Rossetti
mesh_terms: D000273:Adipose Tissue / Q000033:anatomy & histology / Q000502:physiology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001835:Body Weight; D002149:Energy Intake; D005508:Food Deprivation / Q000502:physiology; D005943:Gluconeogenesis / Q000187:drug effects / Q000502:physiology; D006003:Glycogen / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects / Q000502:physiology; D007328:Insulin / Q000502:physiology*; D020738:Leptin; D008099:Liver / Q000502:physiology*; D008297:Male; D011506:Proteins / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014781:Viscera / Q000033:anatomy & histology / Q000502:physiology*
chemical_list: D000318:Adrenergic beta-Agonists; D007328:Insulin; D020738:Leptin; D011506:Proteins; D006003:Glycogen