DOI: 10.1530/JOE-16-0031 Journal of Endocrinology 229:2 http://joe.endocrinology-journals.org © 2016 Society for Endocrinology Printed in Great Britain Published by Bioscientifica Ltd. 145–157 Abstract Mammals meet the increased nutritional demands of lactation through a combination of increased feed intake and a collection of adaptations known as adaptive metabolism (e.g., glucose sparing via insulin resistance, mobilization of endogenous reserves, and increased metabolic effciency via reduced thyroid hormones). In the modern dairy cow, adaptive metabolism predominates over increased feed intake at the onset of lactation and develops concurrently with a reduction in plasma leptin. To address the role of leptin in the adaptive metabolism of early lactation, we asked which adaptations could be countered by a constant 96-h intravenous infusion of human leptin (hLeptin) starting on day 8 of lactation. Compared to saline infusion (Control), hLeptin did not alter energy intake or milk energy output but caused a modest increase in body weight loss. hLeptin reduced plasma glucose by 9% and hepatic glycogen content by 73%, and these effects were associated with a 17% increase in glucose disposal during an insulin tolerance test. hLeptin attenuated the accumulation of triglyceride in the liver by 28% in the absence of effects on plasma levels of the anti-lipolytic hormone insulin or plasma levels of free fatty acids, a marker of lipid mobilization from adipose tissue. Finally, hLeptin increased the plasma concentrations of T 4 and T 3 by nearly 50% without affecting other neurally regulated hormones (i.e., cortisol and luteinizing hormone (LH)). Overall these data implicate the periparturient reduction in plasma leptin as one of the signals promoting conservation of glucose and energy at the onset of lactation in the energy-defcient dairy cow. R A EHRHARDT and others Leptin action in early lactating dairy cows Increased plasma leptin attenuates adaptive metabolism in early lactating dairy cows Richard A Ehrhardt 1 , Andreas Foskolos 2 , Sarah L Giesy 3 , Stephanie R Wesolowski 4 , Christopher S Krumm 3 , W Ronald Butler 3 , Susan M Quirk 3 , Matthew R Waldron 3 and Yves R Boisclair 3 1 Departments of Animal Science and Large Animal Clinical Sciences, Michigan State University, East Lansing, Michigan, USA 2 Institute of Biological, Environmental and Rural Sciences, Aberystwyth University, Aberystwyth, UK 3 Department of Animal Science, Cornell University, Ithaca, New York, USA 4 University of Colorado School of Medicine, Aurora, Colorado, USA Journal of Endocrinology (2016) 229, 145–157 Research Key Words f glucose metabolism f lipid metabolism f liver f thyroid hormone Correspondence should be addressed to Y Boisclair Email yrb1@cornell.edu Introduction In most mammals, the nutrient demands of lactation are met by a combination of increased voluntary feed intake and adaptive metabolism (Vernon et al. 2002). Adaptive metabolism refers to processes preserving metabolic homeostasis during periods of energy insuffciency and includes mobilization of endogenous Downloaded from Bioscientifica.com at 06/07/2020 11:54:50AM via free access